Antioxidant drugs in neurology. The best antioxidants. Preparations "Dibikor" and "Kratal"

Neuroprotectors are a group of pharmaceuticals that protect cells of the nervous system from the effects of negative factors. They help brain structures quickly adapt to pathological changes that occur in the body during stroke, TBI, and neurological diseases. Neuroprotection allows you to preserve the structure and function of neurons. Under the influence of neuroprotective drugs, metabolism in the brain is normalized and the energy supply to nerve cells is improved. Neurologists have been actively prescribing these drugs to patients since the end of the last century.

Neuroprotectors are cytoprotective drugs, the action of which is ensured by the correction of membrane stabilizing, metabolic and mediator balance. Any substance that protects neurons from death has a neuroprotective effect.

Based on the mechanism of action, the following groups of neuroprotectors are distinguished:

Nootropics,
Antioxidants,
Vascular drugs,
Combined action medications,
Adaptogenic agents.

Neuroprotectors or cerebroprotectors are medications that stop or limit damage to brain tissue caused by acute hypoxia and. As a result of the ischemic process, cells die, hypoxic, metabolic and microcirculatory changes occur in all organs and tissues, up to the development of multiple organ failure. To prevent damage to neurons during ischemia, neuroprotectors are used. They improve metabolism, reduce oxidation processes, increase antioxidant protection, and improve hemodynamics. Neuroprotectors help prevent damage to nervous tissue during frequent climate changes, after neuro-emotional stress and overexertion. Thanks to this, they are used not only for therapeutic purposes, but also for preventive purposes.

To treat children, a huge number of neuroprotectors with different mechanisms of action are used in dosages appropriate to age and body weight. These include typical nootropics - Piracetam, vitamins - Neurobion, neuropeptides - Semax, Cerebrolysin.

These drugs increase the resistance of nerve cells to the aggressive effects of traumatic factors, intoxication, etc. These medications have a psychostimulating and sedative effect, reduce the feeling of weakness and depression, and eliminate the manifestations of asthenic syndrome. Neuroprotectors affect higher nervous activity, perception of information, and activate intellectual functions. The mnemotropic effect is to improve memory and learning, while the adaptogenic effect is to increase the body’s ability to withstand harmful environmental influences.

Under the influence of neurotropic drugs, headaches and dizziness decrease, and others disappear. Patients experience clarity of consciousness and an increased level of wakefulness. These drugs do not cause addiction or psychomotor agitation.

Nootropic drugs

Anticoagulants:"Heparin", "Sincumarin", "Warfarin", "Phenilin". These drugs are anticoagulants that disrupt the biosynthesis of blood clotting factors and inhibit their properties.
Antiplatelet"Acetylsalicylic acid" has an effect. It inactivates the enzyme cyclooxygenase and reduces platelet aggregation. In addition, this drug has indirect anticoagulant properties, realized by inhibiting blood clotting factors. "Acetylsalicylic acid" is prescribed for prophylactic purposes to persons with cerebrovascular accidents who have suffered a stroke or myocardial infarction. "Plavix" and "Tiklid" are analogues of "Aspirin". They are prescribed in cases where their “Acetylsalicylic acid” is ineffective or contraindicated.
"Cinnarizine" improves blood fluidity, increases the resistance of muscle fibers to hypoxia, and increases the plasticity of red blood cells. Under its influence, brain vessels dilate, cerebral blood flow improves, and the bioelectrical ability of nerve cells is activated. "Cinnarizine" has an antispasmodic and antihistamine effect, reduces the reaction to certain vasoconstrictors, reduces the excitability of the vestibular apparatus, without affecting blood pressure and heart rate. It relieves spasms of blood vessels and reduces cerebroasthenic manifestations: tinnitus and severe headaches. The medication is prescribed to patients with ischemic stroke, encephalopathy, Meniere's disease, dementia, amnesia and other pathologies accompanied by dizziness and headache.
"Vinpocetine"– a semi-synthetic vasodilator that eliminates hypoxia and increases the resistance of neurons to oxygen deficiency. It reduces platelet aggregation and increases cerebral blood flow, mainly in ischemic areas of the brain. Vinpocetine and Cinnarizine are indirectly acting antihypoxants. Their therapeutic effect is due to the transfer of the body to a lower level of functioning, allowing it to perform full-fledged physical and mental work. The antihypoxic effect of these drugs is considered indirect.
"Trental" dilates blood vessels, improves microcirculation and cerebral blood flow, provides brain cells with the necessary nutrition, and activates metabolic processes. It is effective for osteochondrosis of the cervical spine and other diseases accompanied by a significant deterioration in local blood flow. The main active ingredient of the drug causes relaxation of the smooth muscle walls of blood vessels, increases their diameter, improves the elasticity of the walls of red blood cells, due to which they calmly pass through the vessels of the microvasculature. The drug dilates mainly the blood vessels of the heart and brain structures.

Drugs with combined action

Neuroprotective drugs of combined action have metabolic and vasoactive properties that provide the fastest and best therapeutic effect when treated with low doses of active substances.

"Tiocetam" has a mutually potentiating effect of Piracetam and Thiotriazolin. Along with cerebroprotective and nootropic properties, the drug has antihypoxic, cardioprotective, hepatoprotective, and immunomodulatory effects. Thiocetam is prescribed to patients suffering from diseases of the brain, heart and blood vessels, liver, and viral infections.
"Fezam"- a drug that dilates blood vessels, improves the body's absorption of oxygen, and helps increase its resistance to oxygen deficiency. The medicine contains two components: Piracetam and Cinnarizine. They are neuroprotective agents and increase the resistance of nerve cells to hypoxia. Phezam accelerates protein metabolism and glucose utilization by cells, improves interneuronal transmission in the central nervous system and stimulates blood supply to ischemic areas of the brain. Asthenic, intoxication and psychoorganic syndromes, disorders of thinking, memory and mood are indications for the use of Phezam.

Adaptogens

Adaptogens include herbal products that have a neurotropic effect. The most common among them are: tincture of eleutherococcus, ginseng, Chinese lemongrass. They are designed to combat increased fatigue, stress, anorexia, and hypofunction of the gonads. Adaptogens are used to facilitate acclimatization, prevent colds, and accelerate recovery after acute illnesses.

"Eleutherococcus liquid extract"– a herbal medicine that has a general tonic effect on the human body. This is a dietary supplement, for the production of which the roots of the plant of the same name are used. The neuroprotector stimulates the body's immunity and adaptive capabilities. Under the influence of the drug, drowsiness decreases, metabolism accelerates, appetite improves, and the risk of developing cancer decreases.
"Ginseng tincture" It is of plant origin and has a positive effect on metabolism in the body. The drug stimulates the functioning of the human vascular and nervous systems. It is used as part of general strengthening therapy in weakened patients. “Ginseng tincture” is a metabolic, antiemetic and biostimulating agent that helps the body adapt to atypical stress, increases blood pressure, and lowers blood sugar levels.
"Chinese lemongrass tincture" is a common remedy that allows you to get rid of drowsiness, fatigue and recharge your energy for a long time. This remedy restores the state after depression, provides a surge of physical strength, perfectly tones, has a refreshing and stimulating effect.

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27.03.2015

Based on the results of the II Russian International Congress “Cerebrovascular Pathology and Stroke” (September 17-20, St. Petersburg, Russia)

The role of disturbances in the redox homeostasis of blood and nervous tissue in the pathogenesis of ischemic pathology of the brain and other neurological diseases is very often underestimated by practitioners. At the same time, interest in finding optimal ways of drug correction of oxidative stress does not fade among experimental and clinical researchers.
The 3rd Russian International Congress “Cerebrovascular Pathology and Stroke”, which took place on September 17-20 in St. Petersburg, confirmed the relevance of the topic of antioxidant neuroprotection.
A large number of reports by authoritative Russian scientists were devoted to it, the most interesting of which we present to your attention.

Doctor of Medical Sciences, Professor of the Department of Neurology and Neurosurgery of the Russian State Medical University Alla Borisovna Gekht (Moscow) in her report reviewed the experimental and clinical prerequisites for the use of one of the most studied antioxidants - α-lipoic (thioctic) acid - in the recovery period of cerebral stroke.
– Under physiological conditions, free radical processes are under the control of antioxidant systems and perform a number of vital functions: they participate in the regulation of vascular tone, cell growth, secretion of neurotransmitters, repair of nerve fibers, formation and conduction of nerve impulses, and are part of the memory mechanism and inflammatory response. Under physiological conditions, the process of free radical oxidation of lipids occurs at a low steady-state level, but the picture changes dramatically with excessive production of endogenous or supply of exogenous reactive oxygen species.
Recent studies in the field of pathobiochemistry of acute cerebrovascular accidents have made it possible to identify the main mechanisms of the neurotoxic action of free radicals formed under conditions of underoxidation of glucose during ischemia. These mechanisms are realized through complex cascades of mutually mediated reactions, leading to the acceleration of lipid peroxidation (LPO) of cell membranes and the formation of dysfunctional proteins. The consequences of hyperactivation of lipid peroxidation for nervous tissue include destruction of lysosomes, damage to cytoplasmic membranes, disruption of neurotransmission and, ultimately, death of neurons.
The destructive effects of free radical oxidation are countered by antioxidant defense mechanisms, each of which deserves special attention not only from a biochemist, but also from a clinician. The antioxidant protection system of body tissues can be divided into two levels – physiological and biochemical. The first includes mechanisms for regulating the flow of oxygen into the cell, which are implemented by reducing microcirculation in tissues with an increase in the partial pressure of oxygen in arterial blood (hyperoxic vasospasm). The biochemical level is realized by antioxidant factors themselves, which regulate the production of reactive oxygen species or neutralize them in cells, intercellular fluid and blood.
By origin, antioxidant factors can be enzymes (superoxide dismutase, catalase, glutathione peroxidase), proteins (ferritin, transferrin, ceruloplasmin, albumin), low molecular weight compounds (vitamins A, C, E, ubiquinone, carotenoids, acetylcysteine, α-lipoic acid, etc. .). The mechanisms for regulating oxidative activity also differ. Thus, superoxide dismutase inactivates the aggressive superoxide anion due to the presence in its structure of metals with variable valence - zinc, magnesium, copper. Catalase prevents the accumulation of hydrogen peroxide (H 2 O 2) in cells, which is formed during the aerobic oxidation of reduced flavoproteins. Enzymes of the glutathione system (glutathione peroxidase, -reductase, -transferase) are capable of decomposing lipid hydroperoxides and H 2 O 2, reducing hydroperoxides, and replenishing the pool of reduced glutathione.
Today we will talk about one of the most important components of the body’s antioxidant defense – α-lipoic acid. Its antioxidant properties and ability to modulate the work of other antioxidant systems have been known for a long time. Various studies have shown that α-lipoic acid indirectly restores vitamins C and E (Lakatos B. et al., 1999), increases the level of intracellular glutathione (Busse E., Zimmer G. and et al., 1992), as well as coenzyme Q 10 (Kagan V. and et al., 1990), interacts with glutathione, α-tocopherol, inhibits the acute phase of inflammation and reduces the manifestations of pain (Weicher C.H., Ulrich H., 1989). Experiments on animals show how important the level of endogenous production of this substance is for the development of the nervous tissue of the embryo. A study by Yi and Maeda (2005) demonstrated that mice heterozygous for the gene lacking α-lipoic acid synthase had significantly reduced glutathione levels in red blood cells (a sign of weakened endogenous antioxidant defenses), and homozygous mice died on the 9th day of embryogenesis.
The possibilities of using α-lipoic acid drugs in the treatment of ischemic brain lesions have been well established in experimental models. A recently completed experiment by M. Wayne et al. confirmed the ability of this antioxidant to reduce infarct volume and improve neurological functioning in mice subjected to transient focal ischemia in the middle cerebral artery territory.
In the work of O. Gonzalez-Perez et al. (2002) α-lipoic acid in combination with vitamin E was used in two therapeutic regimens - prophylactic administration and intensive treatment in a model of thromboembolic cerebral infarction in rats. The effect of antioxidants on neurological deficits, glial reactivity and neuronal remodeling in the ischemic penumbra zone was studied. The results of the experiment demonstrated the undeniable advantage of the preventive administration of the studied antioxidants in terms of the degree of improvement of neurological functions, and the inhibition of astrocytic and microglial reactivity was noted both with the prophylactic use of α-lipoic acid with vitamin E, and in the intensive therapy of already developed ischemic brain damage.
After encouraging experimental results opened the way for α-lipoic acid to the clinic, many studies were conducted to study the capabilities of this antioxidant in the treatment of acute cerebrovascular accidents. At our clinic, α-lipoic acid in the form of the drug Berlition produced by Berlin Chemie was studied as an antioxidant for the adjuvant treatment of patients in the recovery period of stroke.
For this category of patients, Berlition was prescribed for 16 weeks orally at a dose of 300 mg 2 times a day or intravenously at a daily dose of 600 mg, followed by switching to oral administration. For placebo control, a group of patients who did not receive antioxidant therapy was recruited. The patients' condition was assessed using the B. Lindmark scale, which fairly fully reflects the degree of neurological dysfunction in stroke. As a result, in patients who received Berlition along with traditional treatment for stroke, after 16 weeks of observation, the increase in points on the rating scale was significantly and significantly higher compared to the placebo group, and the result was comparable in the groups of oral and combined use of the drug, which is very important, since as in real clinical practice, the convenience of the therapeutic regimen plays a significant role. Pharmacoeconomic analysis of the study demonstrated that the cost of one point increase on the Lindmark B scale was significantly lower in the groups of patients receiving Berlition.
The possibility of using drugs with antioxidant properties in the combination of cerebral stroke and diabetes mellitus (DM) deserves special attention. It is known that diabetes significantly complicates the course of stroke. There is also no doubt about the need to prescribe α-lipoic acid drugs for diabetic neuropathy. A reliable evidence base regarding the effect of α-lipoic acid on the course of stroke in patients with diabetes has not been accumulated, but today, undoubtedly, this is one of the promising areas of scientific research in the field of practical application of antioxidant therapy.

Doctor of Medical Sciences, Professor Ella Yurievna Solovyova (Department of Neurology, Faculty of Advanced Training for Physicians, Russian State Medical University, Moscow) presented a report on the topic of correction of oxidative stress in patients with chronic cerebral ischemia.
– An imbalance between the production of free radicals and antioxidant control mechanisms is usually referred to as “oxidative stress.” The list of pathological conditions and diseases in which oxidative stress of the vascular endothelium and nervous tissue plays a key role includes hypoxia, inflammation, atherosclerosis, arterial hypertension, vascular dementia, diabetes mellitus, Alzheimer's disease, parkinsonism and even neuroses.
There are several known reasons for the high sensitivity of brain tissue to oxidative stress. Making up only 2% of the total body weight, the brain utilizes 20-25% of the oxygen the body receives. Conversion of just 0.1% of this amount into superoxide anion turns out to be extremely toxic to neurons. The second reason is the high content of polyunsaturated fatty acids in the brain tissue, a substrate for LPO. There are 1.5 times more phospholipids in the brain than in the liver, and 3-4 times more than in the heart.
The LPO reactions occurring in the brain and other tissues are not fundamentally different from each other, but their intensity in nervous tissue is much higher than in any other tissue. In addition, brain tissue contains a high concentration of metal ions with variable valency, which are necessary for the functioning of enzymes and dopamine receptors. And all this along with an experimentally proven low level of activity of antioxidant factors. Thus, according to Halliwell and Getteridge (1999), the activity of glutathione peroxidase in brain tissue is reduced by more than 2 times, and catalase by hundreds of times compared to the liver.
Chronic cerebral ischemia should be considered if regional cerebral blood flow decreases from 55 ml per 100 g of brain matter per minute (physiological norm) to 45-30 ml. Conventionally, there are two ways of LPO activation in the pathogenesis of chronic cerebrovascular diseases. The first is associated with the actual ischemia of brain tissue and microcirculation disorders, and the second is caused by damage to the cardiovascular system as a whole with atherosclerosis and arterial hypertension, which almost always accompany (and are important risk factors for) cerebrovascular pathology.
Most authors distinguish three stages of LPO activation in chronic cerebral ischemia. If at the first stage there is intensive production of reactive oxygen species along with the mobilization of antioxidant systems, then later stages are characterized by the depletion of protective mechanisms, oxidative modification of the lipid and protein composition of cell membranes, DNA destruction and activation of apoptosis.
When choosing a drug for antioxidant therapy in complex treatment regimens for chronic cerebrovascular accidents, it should be remembered that a universal molecule capable of blocking all pathways for the formation of reactive oxygen species and inhibiting all lipid peroxidation reactions does not exist. Numerous experimental and clinical studies indicate the need for the combined use of several antioxidants with different mechanisms of action, which have the properties of mutually potentiating each other’s effects.
According to the mechanism of action, drugs with antioxidant properties are divided into primary (true) ones, which prevent the formation of new free radicals (these are mainly enzymes that work at the cellular level), and secondary ones, which are capable of capturing already formed radicals. There are few known drugs based on antioxidant enzymes (primary antioxidants). These are mainly substances of natural origin, obtained from bacteria, plants, and animal organs. Some of them are at the stage of preclinical trials, for others the path to neurological practice remains closed. Among the objective reasons for the clinical unpopularity of enzyme preparations, the high risk of side effects, rapid inactivation of enzymes, their high molecular weight and inability to penetrate the blood-brain barrier should be noted.
There is no generally accepted classification of secondary antioxidants. A wide variety of synthetic drugs with claimed antioxidant properties can be divided into two classes based on the solubility of the molecules - hydrophobic, or fat-soluble, acting inside the cell membrane (for example, α-tocopherol, ubiquinone, β-carotene), and hydrophilic, or water-soluble, acting at the boundary separation of aqueous and lipid environments (ascorbic acid, carnosine, acetylcysteine). Every year, the voluminous list of synthetic antioxidants is replenished with new drugs, each of which has its own pharmacodynamic characteristics. Thus, fat-soluble drugs - α-tocopherol acetate, probucol, β-carotene - are characterized by delayed action, their maximum antioxidant effect appears 18-24 hours after entering the body, while water-soluble ascorbic acid begins to act much faster, but in the most rational way is its purpose in combination with vitamin E.
A prominent representative of synthetic antioxidants, capable of penetrating the BBB and working both as part of the cell membrane and in the cell cytoplasm, is α-lipoic acid, the powerful antioxidant potential of which is due to the presence of two thiol groups in the molecule. α-Lipoic acid is able to bind free radical molecules and free tissue iron, preventing its participation in the formation of reactive oxygen species (Fenton reaction). In addition, α-lipoic acid provides support for the work of other antioxidant systems (glutathione, ubiquinone); participates in the metabolic cycles of vitamins C and E; is a cofactor for the oxidative decarboxylation of pyruvic and ketoglutaric acids in the mitochondrial matrix, playing an important role in the energy supply of the cell; helps eliminate metabolic acidosis, facilitating the conversion of lactic acid into pyruvic acid.
Thus, the therapeutic potential of α-lipoic acid in chronic cerebral ischemia is realized through its influence on the energy metabolism of neurons and the reduction of oxidative stress in nervous tissue.
According to many authors, α-lipoic acid is a promising drug for the treatment and prevention of neurological diseases, the pathogenesis of which involves free radical processes (Holmquist L. et al., 2006).
In our study, conducted at the clinical base of the Department of Neurology of the Federal University of the Russian State Medical University in 2006, patients with chronic cerebral ischemia were prescribed the drug α-lipoic acid Berlition, the regimen of which included intravenous drip administration in a daily dose of 300 units during the first 10 days with subsequent transition for oral administration (300 mg of the drug 2 times a day, course 2 weeks). The dynamics of free radical processes during antioxidant therapy were assessed by the concentration of primary (hydroperoxides, diene ketones, diene conjugates) and secondary (malondialdehyde) lipid peroxidation products, carbonyl products of blood plasma, as well as by determining the potential binding capacity of albumin. It should be noted that all patients who took part in the study had a high initial intensity of lipid peroxidation, but at the end of the course of treatment, the levels of secondary lipid peroxidation products in the Berlition group were significantly lower than in the control group. In addition, with the use of Berlition, positive dynamics in the oxidative stability of proteins was noted.
A promising direction in the development of new antioxidant drugs is associated with the synthesis of molecules that have specified properties to influence certain parts of the pathogenesis of oxidative stress, but for their use in widespread clinical practice it is necessary to ensure the possibility of routine laboratory assessment of the state of redox homeostasis of the body.

Vladimir Borisovich Chentsov, head of the resuscitation and intensive care department of infectious diseases clinical hospital No. 2 in Moscow, candidate of medical sciences, shared his clinical experience of using antioxidants in complex intensive therapy of severe bacterial meningitis.
– Between 2003 and 2006, 801 patients were admitted to our department with a diagnosis of purulent meningitis, although additional examination did not confirm the preliminary diagnosis in 135 of them. This is one of the most difficult categories of patients, requiring quick decision-making and adequate resuscitation measures from the first minutes after hospitalization.
Basic treatment of severe purulent meningitis includes artificial ventilation, empirical or etiotropic antibiotic therapy, actions aimed at combating cerebral edema and preventing increased intracranial pressure, correction of water-salt and acid-base status, infusion, anticonvulsant, nootropic and neuroprotective therapy , adequate patient care and prevention of complications. Antioxidant therapy is of no small importance for this pathology, which, along with resuscitation measures, we begin to carry out from the first day of the patient’s stay in the hospital.
In our practice, we use for this purpose the intravenous administration of vitamins E and C in daily doses of 3 ml of a 30% solution and 60 ml of a 5% solution, respectively, Berlition - 600 mg / day, Actovegin in a dose of 250 ml / day, as well as the drug mexidol succinic acid (from the third day 600 mg intravenously with a gradual transition to a dose of 200 mg). Such high doses are due to the need to quickly restore the redox balance in conditions of critical inhibition of endogenous antioxidant systems during acute meningoinfection. At a dose of 3 g per day, vitamin C promotes the regeneration of the antioxidant activity of α-tocopherol. α-Lipoic acid maintains the active state of ubiquinone and glutathione, components of the antioxidant coenzyme Q. Different antioxidants have different points of application in a complex multi-level system of control over oxidative processes. Some of them act in the cytoplasm, others in the nucleus, others in cell membranes, and others in the blood plasma or as part of lipoprotein complexes. α-Lipoic acid occupies a special place in the body's antioxidant defense, since it exhibits its activity in all environments and is also able to penetrate the blood-brain barrier, which is especially important in neurological practice.
An important criterion for the effectiveness of antioxidant therapy is the dynamics of the activity of endogenous antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) in red blood cells or other cells available for study, as well as the content of low molecular weight antioxidants (ascorbic acid, tocopherol, etc.) in plasma. Assessment of the intensity of free radical reactions based on the concentration in the blood of primary, secondary and intermediate lipid peroxidation products (diene conjugates, malondialdehyde), reactive oxygen species can also be used to monitor redox homeostasis. Most of the listed laboratory parameters are available for determination in our clinic, which allows us to monitor the antioxidant therapy regimen and, if necessary, adjust it in accordance with detected changes.
It remains to add that the above scheme of antioxidant therapy, along with timely initiation of basic treatment, can significantly reduce mortality in severe bacterial meningitis.

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Should neuroprotective drugs be used in clinical practice?

Kuznetsov A.N. National Medical and Surgical Center named after N.I. Pirogov, Moscow

The debate regarding the appropriateness of neuroprotective therapy is currently one of the most heated. Several dozen substances have demonstrated a neuroprotective effect in experimental studies, but none of them have confirmed their effectiveness and safety in clinical randomized controlled trials (RCTs). In this regard, in all modern clinical guidelines for the treatment of acute neurological diseases, neuroprotective therapy is not recommended for use. On the other hand, based on empirical experience, as well as within the framework of their own protocols in many medical institutions, and in Russia - in the vast majority of them, drugs with supposed neuroprotective activity are widely used. Why are neuroprotective agents that have proven their effectiveness in experimental studies not subsequently confirmed in clinical trials? Most experts agree that the reason is significant design flaws in the RCTs conducted:

selection of an inadequate “therapeutic window”;
lack of targeted patient selection;
use of obviously insufficient dosages of the drug;
selecting endpoints with low sensitivity and overestimating the magnitude of the possible effect.

Although in experimental studies neuroprotective agents were used immediately after ischemic or traumatic injury (usually within 90 minutes), RCTs enrolled patients within 24 to 48 hours of the acute event. In addition, when selecting patients with stroke, there was no upper and lower threshold for stroke severity, the subtype of ischemic stroke was not taken into account, and the presence or absence of recanalization of the affected artery was not taken into account, while in experimental studies, in almost all cases, neuroprotective therapy was carried out in conditions restored perfusion. This approach to selecting patients and choosing a “therapeutic window” was dictated by the desire to include as many patients as possible in the study, with deliberate disregard for extrapolating the results of experimental studies to the clinical situation, which ultimately led to negative results from RCTs. The use of dosages of drugs in RCTs that were much lower than in the experiment was aimed at minimizing side effects. Treatment efficacy was assessed using clinical endpoints, scales with insufficient clinical sensitivity (eg, Glasgow Coma Scale) were used, and the study design was modeled for a clinically significant effect. Differences of about 10-15% were assumed for the primary endpoints, that is, the effect obtained for thrombolytic therapy within a 3-hour “therapeutic window”, which was obviously an unrealistic result. Statistical calculations show that, using a single neuroprotective agent and clinical endpoints, an effect of 3-5% can be calculated by enrolling 3000-4000 patients using a 3-hour “therapeutic window” and using dosages similar to the experimental ones. An effect of 1-2% is realistically achievable. In any case, these should be large or very large studies in terms of the number of patients included. But in this case the question arises: who will be able to pay for such research? And even if an effect of 1-2% is achieved: who will pay for an expensive drug with minimal effect? Possible ways to overcome this situation are:

use of surrogate endpoints;
the use of several neuroprotective drugs with different points of application;
use of combined thrombolytic and neuroprotective therapy.

Surrogate, that is, non-clinical, endpoints have recently become more and more widely used in RCTs. The most commonly used results are magnetic resonance neuroimaging, which can monitor the extent of damage and serve as a predictor of recovery. But the most promising seems to be the use of combined thrombolytic and neuroprotective therapy in the case of ischemic stroke. Recanalization of an occluded artery will ensure maximum delivery of a neuroprotective agent to the site of damage and, thus, approach the conditions for conducting experimental studies. On the other hand, neuroprotective therapy will help to expand the “therapeutic window” for thrombolysis, as well as reduce reperfusion injury. It should be noted that the experimental studies also had significant shortcomings that contributed to the negative results of the RCT:

the “therapeutic window” was not precisely defined;
the dose range that ensures maximum effectiveness and safety of the substance has not been precisely determined;
the set of markers for the effectiveness of the substance has not been precisely defined.

The main groups of neuroprotective drugs are:

calcium channel blockers;
NMDA and AMPA receptor antagonists;
glutamate release inhibitors;
GABA receptor agonists;
adenosine receptor agonists;
membrane-stabilizing drugs;
neurotrophic (growth) factors;
nitric oxide inhibitors;
antioxidants;
anti-inflammatory drugs;
other drugs.

The action of so-called calcium antagonists or calcium channel blockers (nimodipine (NimotopR) is the most well known in Russia) is aimed at one of the key mechanisms of cell death, both through the mechanism of necrosis and the mechanism of apoptosis - excessive calcium entry into the cell. Drugs in this group block voltage-gated calcium channels, but do not affect calcium channels controlled through receptors (NMDA, AMPA), so their effectiveness is limited. In addition, calcium antagonists have significant side effects, in particular vasodepressor effects. In this regard, numerous RCTs have had negative results. The effectiveness of nimodipine has been demonstrated only in relation to the prevention of vasospasm in subarachnoid hemorrhage. NMDA and AMPA receptor antagonists block receptor-gated calcium channels and thus interrupt the basal flow of calcium into the cell. Receptor activation occurs due to the release of excitotoxic amino acids (mainly glutamate). Substances with high affinity for NMDA receptors (for example, MK-801) showed in RCTs serious psychotomimetic and neurotoxic side effects, since they caused a complete blockade of the receptors, inhibiting their normal physiological activity. Promising drugs are drugs with low affinity for NMDA receptors (memantine, amantadine sulfate, magnesium sulfate and others). An additional important mechanism of action of memantine demonstrated experimentally is the inhibition of hyperphosphorylation of the tau protein and thus the process of neurodegeneration. Some other excitotoxic amino acids, in particular glycine, also cause activation of NMDA receptors, so glycine antagonists have been studied in RCTs, but have not yet confirmed their effectiveness. Currently, RCTs are ongoing to study the effectiveness and safety of AMPA receptor antagonists. The experiment demonstrated the effectiveness of substances that prevent the release of glutamate from presynaptic terminals (lubeluzole), but RCTs have not confirmed their effectiveness. RCTs are ongoing to study the effectiveness of new classes of neuroprotectors - GABA and adenosine receptor antagonists. Among drugs with membrane-stabilizing effects, the effectiveness and safety of cytidine diphosphocholine (cyticholine) is currently being studied in RCTs. A drug used in Russia with a similar mechanism of action is choline alfoscerate (GliatalinR). It should be noted that the effectiveness and safety of this drug have not been studied in RCTs. Great hopes are associated with the use of neurotrophic (growth) factors. One such drug, fibroblast growth factor, was studied in RCTs, but the results were negative. At the same time, the results of experimental studies show the effectiveness of such substances (in particular, the drug CerebrolysinR) in blocking both necrotic and apoptotic neuronal death by inhibiting the calcium-dependent protease calpain. Clinical studies of the neuroprotective activity of antioxidants are ongoing. RCTs of the drug ebselen are currently being conducted. In Russia, antioxidant drugs are used quite widely (MexidolR, CarnitineR and others), but their effectiveness and safety have not been studied in RCTs. Currently, an RCT study of the neuroprotective activity of piracetam, a drug that has been widely used in Russia for a long time, is being conducted. Nitric oxide inhibitors and anti-inflammatory drugs have not yet demonstrated their effectiveness and safety in RCTs. There is no doubt that new RCTs, the design of which will be carried out taking into account previously existing shortcomings, as well as the emergence of new, safer neuroprotective agents, will make it possible to prove the clinical effectiveness of neuroprotection. In this case, the high expectations that the medical community has regarding neuroprotective therapy, as well as the high costs that pharmaceutical companies incurred when creating drugs, will be justified. However, this takes time, so what to do now? The way out of this situation is the use of drugs with supposed neuroprotective activity and known symptomatic effects. Such drugs can also be considered as means that increase the effectiveness of early rehabilitation of patients with severe acute neurological pathology. Early rehabilitation, as is known, is one of the integral components of complex treatment of such patients. Among the drugs used in Russia:

amantadine sulfate (PC-MerzR) has demonstrated its effectiveness in restoring motor functions; has an awakening effect;
memantine (AkatinolR) has been shown to improve cognitive function in RCTs;
CerebrolysinR promotes the restoration of cognitive functions;
choline alfoscerate (GliatilinR) has an awakening effect;
piracetam (PiracetamR, NootropilR, LucetamR) helps improve cognitive functions and has also shown its effectiveness in restoring impaired speech.

It should be noted that one of the areas where neuroprotective drugs can demonstrate their effectiveness is the prevention of neurological complications during surgical interventions that are aggressive to the nervous system (surgeries and manipulations on the heart and cerebral vessels, neurosurgical interventions). Today, when we are on the verge of creating Russian recommendations for the treatment of acute neurological diseases, there is a need to invite Russian specialists to a broad discussion regarding the advisability of using neuroprotective drugs.

Sources:

Fisher M., Brott T. Emerging therapies for acute ischemic stroke: New therapies on trial // Stroke.- 2003.- Vol. 34.- P. 359-361.
Grotta J. Neuroprotection is unlikely to be effective in humans using current trial designs // Stroke.- 2002.- Vol. 33.- P. 306-307.
Lees K. Neuroprotection is unlikely to be effective in humans using current trial designs: An opposing view // Stroke.- 2002.- Vol. 33.- P. 308-309.
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Tolias C., Bullock R. Critical appraisal of neuroprotection trials in head injury: What have we learned? // The Journal of the American Society for Experimental NeuroTherapeutics.- 2004.- Vol. 1.- P. 71-79.
Adams H., del Zoppo G., von Kummer R. Management of stroke: A practical guide for the prevention, evaluation, and treatment of acute stroke.- Professional Communications Inc., 2002.- 303 p.
Gusev E.I., Skvortsova V.I. Cerebral ischemia.- M.: Medicine, 2001.- 327 p.
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Neuroprotection allows you to preserve the structure and function of neurons. Under the influence of neuroprotective drugs, metabolism in the brain is normalized and the energy supply to nerve cells is improved. Neurologists have been actively prescribing these drugs to patients since the end of the last century.

Neuroprotectors are cytoprotective drugs, the action of which is ensured by the correction of membrane-stabilizing, metabolic and mediator balance. Any substance that protects neurons from death has a neuroprotective effect.

Based on the mechanism of action, the following groups of neuroprotectors are distinguished:

Nootropics,
Antioxidants,
Vascular drugs,
Combined action medications,
Adaptogenic agents.

Neuroprotectors or cerebroprotectors are medications that stop or limit damage to brain tissue caused by acute hypoxia and ischemia. As a result of the ischemic process, cells die, hypoxic, metabolic and microcirculatory changes occur in all organs and tissues, up to the development of multiple organ failure. To prevent damage to neurons during ischemia, neuroprotectors are used. They improve metabolism, reduce oxidation processes, increase antioxidant protection, and improve hemodynamics. Neuroprotectors help prevent damage to nervous tissue during frequent climate changes, after neuro-emotional stress and overexertion. Thanks to this, they are used not only for therapeutic purposes, but also for preventive purposes.

To treat children, a huge number of neuroprotectors with different mechanisms of action are used in dosages appropriate to age and body weight. These include typical nootropics - Piracetam, vitamins - Neurobion, neuropeptides - Semax, Cerebrolysin.

These drugs increase the resistance of nerve cells to the aggressive effects of traumatic factors, intoxication, and hypoxia. These medications have a psychostimulating and sedative effect, reduce the feeling of weakness and depression, and eliminate the manifestations of asthenic syndrome. Neuroprotectors affect higher nervous activity, perception of information, and activate intellectual functions. The mnemotropic effect is to improve memory and learning, while the adaptogenic effect is to increase the body’s ability to withstand harmful environmental influences.

Under the influence of neurotropic drugs, blood supply to the brain improves, headaches and dizziness decrease, and other autonomic disorders disappear. Patients experience clarity of consciousness and an increased level of wakefulness. These drugs do not cause addiction or psychomotor agitation.

Nootropic drugs

Nootropics are drugs that stimulate metabolism in nervous tissue and eliminate neuropsychic disorders. They rejuvenate the body, prolong life, activate the learning process and speed up memorization. The term “nootropic” literally means “change the mind” when translated from ancient Greek.

"Piracetam" is the most famous representative of nootropic drugs, widely used in modern traditional medicine for the treatment of psychoneurological diseases. It increases the concentration of ATP in the brain, stimulates the synthesis of RNA and lipids in cells. Piracetam is prescribed to patients during the rehabilitation period after acute cerebral ischemia. The drug is the first nootropic that was synthesized in Belgium in the last century. Scientists have found that this medicine significantly increases mental performance and perception of information.
Cerebrolysin is a hydrolysate obtained from the brain of young pigs. It is a partially degraded whey protein enriched with amino peptides. Due to its low molecular weight, Cerebrolysin quickly penetrates the blood-brain barrier, reaches brain cells and exerts its therapeutic effect. This medicine is of natural origin, due to which it has no contraindications and rarely causes side effects.
"Semax" is a synthetic neuropeptide complex that has a pronounced nootropic effect. It is an analogue of a fragment of adrenocorticotropic hormone, but does not have hormonal activity and does not affect the functioning of the adrenal glands. "Semax" adapts brain function and promotes the formation of resistance to stress damage, hypoxia and ischemia. This medicine is also an antioxidant, antihypoxant and angioprotector.
"Cerakson" is prescribed to patients who have had a stroke. It restores damaged membranes of nerve cells and prevents their further death. For patients with TBI, the drug allows them to quickly recover from post-traumatic coma, reduces the intensity of neurological symptoms and the duration of the rehabilitation period. In patients, after active therapy with the drug, clinical signs such as lack of initiative, memory impairment, difficulties in the process of self-care disappear, and the general level of consciousness increases.
“Picamilon” is a drug that improves cerebral circulation and activates metabolism in brain tissue. The medicine has the properties of an antihypoxant, antioxidant, antiplatelet agent and tranquilizer at the same time. In this case, depression of the central nervous system does not occur, drowsiness and lethargy do not occur. "Picamilon" eliminates symptoms of fatigue and psycho-emotional overload.

Antioxidants

Antioxidants are drugs that neutralize the pathogenic effects of free radicals. After treatment, the body's cells are renewed and healed. Antihypoxants improve the utilization of oxygen circulating in the body and increase the resistance of cells to hypoxia. They prevent, reduce and eliminate the manifestations of oxygen deficiency, maintaining energy metabolism at an optimal level.

List of neuroprotective drugs with antioxidant action:

Mexidol is effective in the fight against hypoxia, ischemia, and convulsions. The drug increases the body's resistance to stress and stimulates its adaptive capabilities to the damaging effects of the environment. This medicine is included in the complex treatment of dyscirculatory changes occurring in the brain. Under the influence of Mexidol, the processes of perception and reproduction of information are improved, especially in older people, and alcohol intoxication of the body is reduced.
"Emoxipin" increases the activity of antioxidant enzymes, reduces the formation of prostaglandins, and prevents thromboaggregation. "Emoxipin" is prescribed to patients with signs of acute cerebral and coronary insufficiency, glaucoma, intraocular hemorrhages, and diabetic retinopathy.
“Glycine” is an amino acid that is a natural metabolite of the brain and affects the functional state of its specialized systems and nonspecific structures. It is a neurotransmitter that regulates metabolic processes in the central nervous system. Under the influence of the drug, psycho-emotional stress is reduced, brain function is improved, the severity of asthenia and pathological dependence on alcohol are reduced. "Glycine" has an anti-stress and sedative effect.
“Glutamic acid” is a drug that stimulates recovery processes in the body, normalizing metabolism and the transmission of nerve impulses. It increases the resistance of brain cells to hypoxia and protects the body from the toxic effects of toxic substances, alcohol, and some medications. The medicine is prescribed to patients with schizophrenia, epilepsy, psychosis, insomnia, encephalitis and meningitis. "Glutamic acid" is included in the complex therapy of cerebral palsy, polio, and Down's disease.
"Complamin" is a neurotropic medicine that improves blood supply to the brain, promotes the flow of oxygenated blood to the brain tissue, and suppresses platelet aggregation. "Complamin" is an indirect antioxidant that activates lipid and carbohydrate metabolism and has a hepatoprotective effect.

Vascular drugs

Classification of the most used vascular drugs: anticoagulants, antiplatelet agents, vasodilators, calcium channel blockers.

Anticoagulants: Heparin, Sincumarin, Warfarin, Phenilin. These drugs are anticoagulants that disrupt the biosynthesis of blood clotting factors and inhibit their properties.
Acetylsalicylic acid has an antiplatelet effect. It inactivates the enzyme cyclooxygenase and reduces platelet aggregation. In addition, this drug has indirect anticoagulant properties, realized by inhibiting blood clotting factors. "Acetylsalicylic acid" is prescribed for prophylactic purposes to persons with cerebrovascular accidents who have suffered a stroke or myocardial infarction. "Plavix" and "Tiklid" are analogues of "Aspirin". They are prescribed in cases where their “Acetylsalicylic acid” is ineffective or contraindicated.
“Cinnarizine” improves blood fluidity, increases the resistance of muscle fibers to hypoxia, and increases the plasticity of erythrocytes. Under its influence, brain vessels dilate, cerebral blood flow improves, and the bioelectrical ability of nerve cells is activated. "Cinnarizine" has an antispasmodic and antihistamine effect, reduces the reaction to certain vasoconstrictors, reduces the excitability of the vestibular apparatus, without affecting blood pressure and heart rate. It relieves spasms of blood vessels and reduces cerebroasthenic manifestations: tinnitus and severe headaches. The medication is prescribed to patients with ischemic stroke, encephalopathy, Meniere's disease, dementia, amnesia and other pathologies accompanied by dizziness and headache.

Drugs with combined action

Neuroprotective drugs of combined action have metabolic and vasoactive properties that provide the fastest and best therapeutic effect when treated with low doses of active substances.

"Tiocetam" has a mutually potentiating effect of "Piracetam" and "Tiotriazolin". Along with cerebroprotective and nootropic properties, the drug has antihypoxic, cardioprotective, hepatoprotective, and immunomodulatory effects. Thiocetam is prescribed to patients suffering from diseases of the brain, heart and blood vessels, liver, and viral infections.
"Phesam" is a drug that dilates blood vessels, improves the body's absorption of oxygen, and helps increase its resistance to oxygen deficiency. The medicine contains two components: Piracetam and Cinnarizine. They are neuroprotective agents and increase the resistance of nerve cells to hypoxia. Phezam accelerates protein metabolism and glucose utilization by cells, improves interneuronal transmission in the central nervous system and stimulates blood supply to ischemic areas of the brain. Asthenic, intoxication and psychoorganic syndromes, disorders of thinking, memory and mood are indications for the use of Phezam.

Adaptogens

“Liquid extract of Eleutherococcus” is a herbal medicine that has a general tonic effect on the human body. This is a dietary supplement, for the production of which the roots of the plant of the same name are used. The neuroprotector stimulates the body's immunity and adaptive capabilities. Under the influence of the drug, drowsiness decreases, metabolism accelerates, appetite improves, and the risk of developing cancer decreases.
“Ginseng tincture” is of plant origin and has a positive effect on metabolism in the body. The drug stimulates the functioning of the human vascular and nervous systems. It is used as part of general strengthening therapy in weakened patients. “Ginseng tincture” is a metabolic, antiemetic and biostimulating agent that helps the body adapt to atypical stress, increases blood pressure, and lowers blood sugar levels.
“Chinese lemongrass tincture” is a common remedy that allows you to get rid of drowsiness, fatigue and recharge your batteries for a long time. This remedy restores the state after depression, provides a surge of physical strength, perfectly tones, has a refreshing and stimulating effect.

Antioxidant therapy in neurological practice: prerequisites for widespread use and clinical experience of Russian colleagues

Based on the results of the II Russian International Congress “Cerebrovascular Pathology and Stroke” (September 17-20, St. Petersburg, Russia)

The 3rd Russian International Congress “Cerebrovascular Pathology and Stroke”, which took place in September in St. Petersburg, confirmed the relevance of the topic of antioxidant neuroprotection.

A large number of reports by authoritative Russian scientists were devoted to it, the most interesting of which we present to your attention.

– Under physiological conditions, free radical processes are under the control of antioxidant systems and perform a number of vital functions: they participate in the regulation of vascular tone, cell growth, secretion of neurotransmitters, repair of nerve fibers, formation and conduction of nerve impulses, and are part of the memory mechanism and inflammatory response. Under physiological conditions, the process of free radical oxidation of lipids occurs at a low steady-state level, but the picture changes dramatically with excessive production of endogenous or supply of exogenous reactive oxygen species.

Recent studies in the field of pathobiochemistry of acute cerebrovascular accidents have made it possible to identify the main mechanisms of the neurotoxic action of free radicals formed under conditions of underoxidation of glucose during ischemia. These mechanisms are realized through complex cascades of mutually mediated reactions, leading to the acceleration of lipid peroxidation (LPO) of cell membranes and the formation of dysfunctional proteins. The consequences of hyperactivation of lipid peroxidation for nervous tissue include destruction of lysosomes, damage to cytoplasmic membranes, disruption of neurotransmission and, ultimately, death of neurons.

The destructive effects of free radical oxidation are countered by antioxidant defense mechanisms, each of which deserves special attention not only from a biochemist, but also from a clinician. The antioxidant protection system of body tissues can be divided into two levels – physiological and biochemical. The first includes mechanisms for regulating the flow of oxygen into the cell, which are implemented by reducing microcirculation in tissues with an increase in the partial pressure of oxygen in arterial blood (hyperoxic vasospasm). The biochemical level is realized by antioxidant factors themselves, which regulate the production of reactive oxygen species or neutralize them in cells, intercellular fluid and blood.

By origin, antioxidant factors can be enzymes (superoxide dismutase, catalase, glutathione peroxidase), proteins (ferritin, transferrin, ceruloplasmin, albumin), low molecular weight compounds (vitamins A, C, E, ubiquinone, carotenoids, acetylcysteine, α-lipoic acid, etc. .). The mechanisms for regulating oxidative activity also differ. Thus, superoxide dismutase inactivates the aggressive superoxide anion due to the presence in its structure of metals with variable valence - zinc, magnesium, copper. Catalase prevents the accumulation of hydrogen peroxide (H 2 O 2) in cells, which is formed during the aerobic oxidation of reduced flavoproteins. Enzymes of the glutathione system (glutathione peroxidase, -reductase, -transferase) are capable of decomposing lipid hydroperoxides and H 2 O 2, reducing hydroperoxides, and replenishing the pool of reduced glutathione.

Today we will talk about one of the most important components of the body’s antioxidant defense – α-lipoic acid. Its antioxidant properties and ability to modulate the work of other antioxidant systems have been known for a long time. Various studies have shown that α-lipoic acid indirectly restores vitamins C and E (Lakatos B. et al., 1999), increases the level of intracellular glutathione (Busse E., Zimmer G. and et al., 1992), as well as coenzyme Q 10 (Kagan V. and et al., 1990), interacts with glutathione, α-tocopherol, inhibits the acute phase of inflammation and reduces the manifestations of pain (Weicher C.H., Ulrich H., 1989). Experiments on animals show how important the level of endogenous production of this substance is for the development of the nervous tissue of the embryo. A study by Yi and Maeda (2005) demonstrated that mice heterozygous for the gene lacking α-lipoic acid synthase had significantly reduced glutathione levels in red blood cells (a sign of weakened endogenous antioxidant defenses), and homozygous mice died on the 9th day of embryogenesis.

The possibilities of using α-lipoic acid drugs in the treatment of ischemic brain lesions have been well established in experimental models. A recently completed experiment by M. Wayne et al. confirmed the ability of this antioxidant to reduce infarct volume and improve neurological functioning in mice subjected to transient focal ischemia in the middle cerebral artery territory.

In the work of O. Gonzalez-Perez et al. (2002) α-lipoic acid in combination with vitamin E was used in two therapeutic regimens - prophylactic administration and intensive treatment in a model of thromboembolic cerebral infarction in rats. The effect of antioxidants on neurological deficits, glial reactivity and neuronal remodeling in the ischemic penumbra zone was studied. The results of the experiment demonstrated the undeniable advantage of the preventive administration of the studied antioxidants in terms of the degree of improvement of neurological functions, and the inhibition of astrocytic and microglial reactivity was noted both with the prophylactic use of α-lipoic acid with vitamin E, and in the intensive therapy of already developed ischemic brain damage.

After encouraging experimental results opened the way for α-lipoic acid to the clinic, many studies were conducted to study the capabilities of this antioxidant in the treatment of acute cerebrovascular accidents. At our clinic, α-lipoic acid in the form of the drug Berlition produced by Berlin Chemie was studied as an antioxidant for the adjuvant treatment of patients in the recovery period of stroke.

For this category of patients, Berlition was prescribed for 16 weeks orally at a dose of 300 mg 2 times a day or intravenously at a daily dose of 600 mg, followed by switching to oral administration. For placebo control, a group of patients who did not receive antioxidant therapy was recruited. The patients' condition was assessed using the B. Lindmark scale, which fairly fully reflects the degree of neurological dysfunction in stroke. As a result, in patients who received Berlition along with traditional treatment for stroke, after 16 weeks of observation, the increase in points on the rating scale was significantly and significantly higher compared to the placebo group, and the result was comparable in the groups of oral and combined use of the drug, which is very important, since as in real clinical practice, the convenience of the therapeutic regimen plays a significant role. Pharmacoeconomic analysis of the study demonstrated that the cost of one point increase on the Lindmark B scale was significantly lower in the groups of patients receiving Berlition.

The possibility of using drugs with antioxidant properties in the combination of cerebral stroke and diabetes mellitus (DM) deserves special attention. It is known that diabetes significantly complicates the course of stroke. There is also no doubt about the need to prescribe α-lipoic acid drugs for diabetic neuropathy. A reliable evidence base regarding the effect of α-lipoic acid on the course of stroke in patients with diabetes has not been accumulated, but today, undoubtedly, this is one of the promising areas of scientific research in the field of practical application of antioxidant therapy.

Doctor of Medical Sciences, Professor Ella Yuryevna Solovyova (Department of Neurology, Faculty of Advanced Medical Studies, Russian State Medical University, Moscow) presented a report on the topic of correction of oxidative stress in patients with chronic cerebral ischemia.

– An imbalance between the production of free radicals and antioxidant control mechanisms is usually referred to as “oxidative stress.” The list of pathological conditions and diseases in which oxidative stress of the vascular endothelium and nervous tissue plays a key role includes hypoxia, inflammation, atherosclerosis, arterial hypertension, vascular dementia, diabetes mellitus, Alzheimer's disease, parkinsonism and even neuroses.

There are several known reasons for the high sensitivity of brain tissue to oxidative stress. Making up only 2% of the total body weight, the brain utilizes 20-25% of the oxygen the body receives. Conversion of just 0.1% of this amount into superoxide anion turns out to be extremely toxic to neurons. The second reason is the high content of polyunsaturated fatty acids in the brain tissue, a substrate for LPO. There are 1.5 times more phospholipids in the brain than in the liver, and 3-4 times more than in the heart.

The LPO reactions occurring in the brain and other tissues are not fundamentally different from each other, but their intensity in nervous tissue is much higher than in any other tissue. In addition, brain tissue contains a high concentration of metal ions with variable valency, which are necessary for the functioning of enzymes and dopamine receptors. And all this along with an experimentally proven low level of activity of antioxidant factors. Thus, according to Halliwell and Getteridge (1999), the activity of glutathione peroxidase in brain tissue is reduced by more than 2 times, and catalase by hundreds of times compared to the liver.

Chronic cerebral ischemia should be considered if regional cerebral blood flow decreases from 55 ml per 100 g of brain matter per minute (physiological norm) to ml. Conventionally, there are two ways of LPO activation in the pathogenesis of chronic cerebrovascular diseases. The first is associated with the actual ischemia of brain tissue and microcirculation disorders, and the second is caused by damage to the cardiovascular system as a whole with atherosclerosis and arterial hypertension, which almost always accompany (and are important risk factors for) cerebrovascular pathology.

Most authors distinguish three stages of LPO activation in chronic cerebral ischemia. If at the first stage there is intensive production of reactive oxygen species along with the mobilization of antioxidant systems, then later stages are characterized by the depletion of protective mechanisms, oxidative modification of the lipid and protein composition of cell membranes, DNA destruction and activation of apoptosis.

When choosing a drug for antioxidant therapy in complex treatment regimens for chronic cerebrovascular accidents, it should be remembered that a universal molecule capable of blocking all pathways for the formation of reactive oxygen species and inhibiting all lipid peroxidation reactions does not exist. Numerous experimental and clinical studies indicate the need for the combined use of several antioxidants with different mechanisms of action, which have the properties of mutually potentiating each other’s effects.

According to the mechanism of action, drugs with antioxidant properties are divided into primary (true) ones, which prevent the formation of new free radicals (these are mainly enzymes that work at the cellular level), and secondary ones, which are capable of capturing already formed radicals. There are few known drugs based on antioxidant enzymes (primary antioxidants). These are mainly substances of natural origin, obtained from bacteria, plants, and animal organs. Some of them are at the stage of preclinical trials, for others the path to neurological practice remains closed. Among the objective reasons for the clinical unpopularity of enzyme preparations, the high risk of side effects, rapid inactivation of enzymes, their high molecular weight and inability to penetrate the blood-brain barrier should be noted.

There is no generally accepted classification of secondary antioxidants. A wide variety of synthetic drugs with claimed antioxidant properties can be divided into two classes based on the solubility of the molecules - hydrophobic, or fat-soluble, acting inside the cell membrane (for example, α-tocopherol, ubiquinone, β-carotene), and hydrophilic, or water-soluble, acting at the boundary separation of aqueous and lipid environments (ascorbic acid, carnosine, acetylcysteine). Every year, the voluminous list of synthetic antioxidants is replenished with new drugs, each of which has its own pharmacodynamic characteristics. Thus, fat-soluble drugs - α-tocopherol acetate, probucol, β-carotene - are characterized by a delayed action, their maximum antioxidant effect appears one hour after entering the body, while water-soluble ascorbic acid begins to act much faster, but the most rational is its administration in combinations with vitamin E.

A prominent representative of synthetic antioxidants, capable of penetrating the BBB and working both as part of the cell membrane and in the cell cytoplasm, is α-lipoic acid, the powerful antioxidant potential of which is due to the presence of two thiol groups in the molecule. α-Lipoic acid is able to bind free radical molecules and free tissue iron, preventing its participation in the formation of reactive oxygen species (Fenton reaction). In addition, α-lipoic acid provides support for the work of other antioxidant systems (glutathione, ubiquinone); participates in the metabolic cycles of vitamins C and E; is a cofactor for the oxidative decarboxylation of pyruvic and ketoglutaric acids in the mitochondrial matrix, playing an important role in the energy supply of the cell; helps eliminate metabolic acidosis, facilitating the conversion of lactic acid into pyruvic acid.

Thus, the therapeutic potential of α-lipoic acid in chronic cerebral ischemia is realized through its influence on the energy metabolism of neurons and the reduction of oxidative stress in nervous tissue.

In our study, conducted at the clinical base of the Department of Neurology of the Federal University of the Russian State Medical University in 2006, patients with chronic cerebral ischemia were prescribed the drug α-lipoic acid Berlition, the regimen of which included intravenous drip administration in a daily dose of 300 units during the first 10 days with subsequent transition for oral administration (300 mg of the drug 2 times a day, course 2 weeks). The dynamics of free radical processes during antioxidant therapy were assessed by the concentration of primary (hydroperoxides, diene ketones, diene conjugates) and secondary (malondialdehyde) lipid peroxidation products, carbonyl products of blood plasma, as well as by determining the potential binding capacity of albumin. It should be noted that all patients who took part in the study had a high initial intensity of lipid peroxidation, but at the end of the course of treatment, the levels of secondary lipid peroxidation products in the Berlition group were significantly lower than in the control group. In addition, with the use of Berlition, positive dynamics in the oxidative stability of proteins was noted.

A promising direction in the development of new antioxidant drugs is associated with the synthesis of molecules that have specified properties to influence certain parts of the pathogenesis of oxidative stress, but for their use in widespread clinical practice it is necessary to ensure the possibility of routine laboratory assessment of the state of redox homeostasis of the body.

– Between 2003 and 2006, 801 patients were admitted to our department with a diagnosis of purulent meningitis, although additional examination did not confirm the preliminary diagnosis in 135 of them. This is one of the most difficult categories of patients, requiring quick decision-making and adequate resuscitation measures from the first minutes after hospitalization.

Basic treatment of severe purulent meningitis includes artificial ventilation, empirical or etiotropic antibiotic therapy, actions aimed at combating cerebral edema and preventing increased intracranial pressure, correction of water-salt and acid-base status, infusion, anticonvulsant, nootropic and neuroprotective therapy , adequate patient care and prevention of complications. Antioxidant therapy is of no small importance for this pathology, which, along with resuscitation measures, we begin to carry out from the first day of the patient’s stay in the hospital.

In our practice, we use for this purpose the intravenous administration of vitamins E and C in daily doses of 3 ml of a 30% solution and 60 ml of a 5% solution, respectively, Berlition - 600 mg / day, Actovegin in a dose of 250 ml / day, as well as the drug mexidol succinic acid (from the third day 600 mg intravenously with a gradual transition to a dose of 200 mg). Such high doses are due to the need to quickly restore the redox balance in conditions of critical inhibition of endogenous antioxidant systems during acute meningoinfection. At a dose of 3 g per day, vitamin C promotes the regeneration of the antioxidant activity of α-tocopherol. α-Lipoic acid maintains the active state of ubiquinone and glutathione, components of the antioxidant coenzyme Q. Different antioxidants have different points of application in a complex multi-level system of control over oxidative processes. Some of them act in the cytoplasm, others in the nucleus, others in cell membranes, and others in the blood plasma or as part of lipoprotein complexes. α-Lipoic acid occupies a special place in the body's antioxidant defense, since it exhibits its activity in all environments and is also able to penetrate the blood-brain barrier, which is especially important in neurological practice.

An important criterion for the effectiveness of antioxidant therapy is the dynamics of the activity of endogenous antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) in red blood cells or other cells available for study, as well as the content of low molecular weight antioxidants (ascorbic acid, tocopherol, etc.) in plasma. Assessment of the intensity of free radical reactions based on the concentration in the blood of primary, secondary and intermediate lipid peroxidation products (diene conjugates, malondialdehyde), reactive oxygen species can also be used to monitor redox homeostasis. Most of the listed laboratory parameters are available for determination in our clinic, which allows us to monitor the antioxidant therapy regimen and, if necessary, adjust it in accordance with detected changes.

It remains to add that the above scheme of antioxidant therapy, along with timely initiation of basic treatment, can significantly reduce mortality in severe bacterial meningitis.

Number:
No. 20 October - General therapeutic issue

stats behind the topic

According to data from other authors, in coloproctology, hemorrhoids are one of the leading places in the structure of illness, the prevalence of which is high and becomes ill per 1000 adult population. In women, hemorrhoids appear or worsen, especially during pregnancy, pregnancy, or in the postpartum period. According to the statistics, women who have not been abused suffer from hemorrhoids 5 times more often than those who have been abused at least once.

The intensity and type of intra-abdominal infectious obstruction with extensive purulent peritonitis significantly influences the effectiveness of treatment of patients. The adequacy and appropriateness of the surgical procedure performed are paramount in preventing illness. The method of investigation was to evaluate the effectiveness of decamethoxin stagnation as a solution for the sanitation of the cerebral effusion (CP) in patients with purulent peritonitis. .

The relevance of the problem of chronic venous insufficiency (CVI) is primarily due to the widespread prevalence of the disease. According to statistics, the occurrence of this pathology among the working population exceeds 70%. In more than 50% of cases, the cause of the development of trophic ulcers of the lower extremities (LC) is CVI. Trophic disorders that arise against this background lead to long-term incapacity and disability among people of the most active working age, to limitation of the main categories of life activity - from the ability to work to the ability to move independently and take care of themselves, which significantly reduces their quality of life.

The availability of varied surgical operations and the widespread introduction of minimally invasive procedures into practice creates a dilemma when choosing a method for surgical treatment of patients with folded pseudocysts (PCs) of the subglottic gland (PZ). ). According to the standard in the licumentary folded PC PZ є laparotomic delivery, when frozen, low important postoperative complications are avoided, which resulted in the number of patients in the hospital and mortality in the postoperative patient. Iodine. Regardless of the fact that laparotomy is not an elective operation, it does not allow improving the results of surgical treatment of patients with complex PC PZ. Belshii XIRURGIV VIDAYUT SIME PERSEVAGEMENT METHODS OF LIKEVANNE of the LIKENENCH PC PZ, through those strokes in the sabbath vipades of the zbillei vіrogydnost, the navigation of Laparotoma, and ilodi - є residual.

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Oxidative stress and the use of antioxidants in neurology

Anatoly Ivanovich Fedin

Professor, head Department of Neurology and Neurosurgery FUV RSMU

One of the universal mechanisms of cell activity and processes occurring in the intercellular space is the formation of free radicals (FR). CPs constitute a special class of chemical substances, different in their atomic composition, but characterized by the presence of an unpaired electron in the molecule. CPs are essential companions of oxygen and have high chemical activity.

The processes of free radical oxidation should be considered as a necessary metabolic link in oxidative phosphorylation, biosynthesis of prostaglandins and nucleic acids, and immune reactions. Nitric oxide acts as a neurotransmitter and takes part in the regulation of blood flow. SRs are formed during the peroxidation of unsaturated fatty acids with the regulation of the physical properties of biological membranes.

On the other hand, free radical oxidation is a universal pathophysiological phenomenon in many pathological conditions. Oxygen for any cell, especially for a neuron, is the leading energy acceptor in the respiratory mitochondrial chain. By binding to the iron atom of cytochrome oxidase, the oxygen molecule undergoes four-electron reduction and turns into water. But under conditions of disruption of energy-generating processes and incomplete reduction of oxygen, the formation of highly reactive and therefore toxic SRs or products that generate them occurs.

The relative availability and ease of formation of CP under conditions of incomplete oxygen reduction is associated with the unique properties of its molecules. In chemical compounds, oxygen atoms are divalent. The simplest illustration of this is the well-known formula of the water molecule. However, in the oxygen molecule, both atoms are connected only by a single bond, and the remaining one electron on each oxygen atom is free. The main stable form of oxygen is the so-called triplet oxygen, in the molecule of which both unpaired electrons are parallel, but their spins (valences) are directed in the same direction. When the spins are arranged in different directions in the molecule, singlet oxygen is formed, which, due to its chemical properties, is unstable and toxic to biological substances.

The formation of SR is promoted by many processes that accompany the vital activity of the body: stress, exogenous and endogenous intoxication, the influence of man-made environmental pollution and ionizing radiation. According to some authors, SRs are involved in the pathogenesis of more than 100 different diseases. The pathological effect of CPs is primarily associated with their influence on the structural state and functions of biological membranes. It has been established that tissue hypoxia and ischemia are accompanied by activation of lipid peroxidation. As is known, cell membranes contain a large number of phospholipids. When a CP appears in the membrane, the probability of its interaction with a fatty acid increases as the number of multiple bonds increases. Since unsaturated fatty acids provide membranes with greater mobility, their changes as a result of lipid peroxidation processes lead to both an increase in membrane viscosity and a partial loss of barrier functions.

At present, there is no doubt about the fact that the functional properties of a number of enzymes, carbohydrates and proteins, including DNA and RNA proteins, change under the influence of SR. The brain is particularly sensitive to overproduction of SR and to the so-called oxidative stress. Oxidative stress, leading to hyperproduction of CP and destruction of membranes associated with activation of phospholipase hydrolysis, plays a particularly significant role in the pathogenetic mechanisms of cerebral ischemia. In these cases, the main factor damaging mitochondrial, plasma and microsomal membranes is the highly active hydroxyl radical OH. Increased production of SR, initiated during cerebral ischemia by arachidonic acid, is one of the causes of prolonged vasospasm and disruption of cerebral autoregulation, as well as the progression of post-ischemic edema and swelling due to the disintegration of neurons and damage to membrane pumps. During ischemia, due to energy deficiency, the activity of antioxidant enzymes decreases: superoxide dismutase, catalase and glutathione peroxidase. At the same time, the amount of almost all water- and fat-soluble antioxidants decreases.

In recent years, oxidative stress has also been considered as one of the most significant factors in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease and other types of dementia, Parkinson's disease, amyotrophic lateral sclerosis, epilepsy and multiple sclerosis.

Along with free radical oxidation, during the functioning of biological objects, substances with antioxidant effects are produced from groups of radicals, which are called stable radicals. Such radicals are not capable of abstracting hydrogen atoms from most molecules that make up the cell, but they can perform this operation with special molecules that have weakly bound hydrogen atoms. The class of chemical compounds under consideration is called antioxidants (AO), since their mechanism of action is based on the inhibition of free radical processes in tissues. Unlike unstable SRs, which have a damaging effect on cells, stable SRs inhibit the development of destructive processes.

The physiological antioxidant system existing in the body is a cumulative hierarchy of protective mechanisms of cells, tissues, organs and systems aimed at preserving and maintaining the body’s reactions within normal limits, including under conditions of ischemia and stress. The preservation of oxidative-antioxidant balance, which is the most important mechanism of homeostasis of living systems, is realized both in the fluid media of the body (blood, lymph, intercellular and intracellular fluid), and in the structural elements of the cell, primarily in membrane structures (plasma, endoplasmic and mitochondrial, cellular membranes). Antioxidative intracellular enzymes include superoxide dismutase, which inactivates the superoxide radical, and catalase, which decomposes hydrogen peroxide.

Currently known biological and chemically synthesized AOs are divided into fat-soluble and water-soluble. Fat-soluble AOs are localized where the target substrates for attack by CPs and peroxides are located—the biological structures that are most vulnerable to peroxidation processes. These structures include primarily biological membranes and blood lipoproteins, and their main targets are unsaturated fatty acids.

Among the fat-soluble AOs, the most famous is tocopherol, which, interacting with the hydroxyl radical OH, has an inhibitory effect on singlet oxygen. Among water-soluble AOs, glutathione is important, playing a key role in protecting cells from toxic oxygen intermediates. The second most important among water-soluble antioxidant systems is the ascorbic acid system, which is especially important for the antioxidant protection of brain structures.

The most adequate synergist and almost ubiquitous companion of ascorbic acid is a system of physiologically active phenolic compounds. The number of known phenolic compounds exceeds 20,000. They are found in significant quantities in all living plant organisms, accounting for 1–2% of biomass or more and performing a variety of biological functions. The greatest variety of chemical properties and biological activity are distinguished by phenolic compounds with two or more hydroxyl groups in the benzene ring. These classes of phenolic compounds form a buffer redox system under physiological conditions. The antioxidant properties of phenols are associated with the presence in their structure of weak phenolic hydroxyl groups, which easily give up their hydrogen atom when interacting with CP. In this case, phenols act as SR traps, turning themselves into low-active phenoxyl radicals. In the fight against SR, not only antioxidant substances produced by the body take part, but also antioxidants supplied as part of food. AO also includes minerals (compounds of selenium, magnesium, copper), some amino acids, and plant polyphenols (flavonoids).

It should be noted that in order to gain the physiologically necessary minimum of AO from products of plant origin, their specific weight in daily nutrition must significantly exceed all other food components.

The modern diet is dominated by refined and processed foods that lack valuable natural qualities. Taking into account the constantly increasing need for AO due to the influence of unfavorable environmental factors, the reason for the chronic deficiency of AO in a significant part of the population becomes clear.

In the clinic, some of the most commonly used natural antioxidants are tocopherol, ascorbic acid and methionine. The concept of the antioxidant effect of tocopherol was formulated by Tarpel A.L. in 1953. By actively protecting cell membranes with the hydroxyl group of its benzene core, tocopherol helps maintain the activity of membrane-bound enzymes, while simultaneously increasing the level of natural lipid AO. By interacting with the hydroxyl radical and exerting a “quenching” effect on singlet oxygen, tocopherol performs several functions that together give an antioxidant effect. Tocopherol is not synthesized in the body and belongs to the group of vitamins (vitamin E). Vitamin E is one of the most important universal fat-soluble amino acids and plays the role of a natural immunomodulator, stimulating blast transformation of T-lymphocytes, normalizing cellular and humoral immunity.

It is advisable to include alpha-tocopherol, ascorbic acid and methionine in the complex of rehabilitation treatment of many neurological diseases and their consequences. Their disadvantages are weak antioxidant pharmacokinetics and the need for long-term (several weeks) use of these drugs to develop the antioxidant effect.

Currently, synthetic drugs with AO properties are widely used in clinical, including neurological practice. Of the synthetic antioxidant substances, dibunol, a fat-soluble drug belonging to the class of shielded phenols, has been well studied. At dosages of 20–50 mg/kg, its quite pronounced anti-ischemic, anti-hypoxic and angioprotective effect is shown. The mechanism of action of another fat-soluble representative of shielded phenols, probucol, is due to the inhibition of peroxidation of low-density lipoproteins, which significantly reduces their atherogenicity. The antiatherogenic effect of probucol has been shown in patients with diabetes mellitus. The latest generation phenolic AO is the drug olifen, the molecule of which contains more than 10 phenolic hydroxyl groups that can ensure the binding of a large number of CPs. The drug has a pronounced prolonged antioxidant effect, promoting the activation of microcirculation and metabolic processes in the body, including in brain tissue, including due to its pronounced membrane-protective effect.

In recent years, the effect of succinic acid, its salts and esters, which are universal intracellular metabolites, has been studied. Succinic acid, contained in organs and tissues, is a product of the 5th reaction and a substrate of the 6th reaction of the tricarboxylic acid cycle. The oxidation of succinic acid in the 6th reaction of the Krebs cycle is carried out using succinate dehydrogenase. Performing a catalytic function in relation to the Krebs cycle, succinic acid reduces the concentration in the blood of other intermediates of this cycle - lactate, pyruvate and citrate, produced in the early stages of hypoxia.

The phenomenon of rapid oxidation of succinic acid by succinate dehydrogenase, accompanied by ATP-dependent reduction of the pool of pyrimidine dinucleotides, is called “monopolization of the respiratory chain,” the biological significance of which lies in the rapid resynthesis of ATP. The so-called aminobutyrate shunt (Roberts cycle) operates in nervous tissue, during which succinic acid is formed from aminobutyric acid (GABA) through the intermediate stage of succinic aldehyde. Under conditions of stress and hypoxia, the formation of succinic acid is also possible in the reaction of oxidative deamination of ketaglutaric acid in the liver.

The antihypoxic effect of succinic acid is due to its effect on the transport of mediator amino acids, as well as an increase in the content of GABA in the brain during the functioning of the Roberts shunt. Succinic acid in the body as a whole normalizes the content of histamine and serotonin and increases microcirculation in organs and tissues, primarily in brain tissue, without affecting blood pressure and heart function. The anti-ischemic effect of succinic acid is associated not only with the activation of succinate dehydrogenase oxidation, but also with the restoration of the activity of the key redox enzyme of the mitochondrial respiratory chain - cytochrome oxidase.

Currently, the study of the use of succinic acid derivatives to reduce the severity of ischemic brain damage is ongoing. One of these drugs is the domestic drug Mexidol. Mexidol is an AO - SR inhibitor, a membrane protector, reduces the activation of lipid peroxidation, and increases the activity of the physiological antioxidant system as a whole. Mexidol is also an antihypoxant with direct energizing action, activating the energy-synthesizing functions of mitochondria and improving energy metabolism in the cell.

The drug has a lipid-lowering effect, reducing the level of total cholesterol and low-density lipoproteins. Mexidol has a modulating effect on membrane-bound enzymes, ion channels - neurotransmitter transporters, receptor complexes, including benzodiazepine, GABA and acetylcholine, improves synaptic transmission and, consequently, the interconnection of brain structures. In addition, Mexidol improves and stabilizes metabolism and blood supply to the brain, corrects disorders in the regulatory and microcirculatory systems, improves the rheological properties of blood, suppresses platelet aggregation, and improves the functioning of the immune system.

The high activity of succinic acid has found application in the detoxification solution Reamberin 1.5% for infusion, which contains a salt of succinic acid and trace elements in optimal concentrations (magnesium chloride, potassium chloride and sodium chloride). The drug has a pronounced antihypoxic and antioxidant effect, having a positive effect on aerobic biochemical processes in the cell during ischemia and hypoxia, reducing the production of CP and restoring the energy potential of the cell. The drug inactivates the enzymatic processes of the Krebs cycle and promotes the utilization of fatty acids and glucose by cells, normalizes the acid-base balance and gas composition of the blood. The drug can be used as an energy corrector in patients with primary and secondary ischemic brain lesions, including against the background of the development of multiple organ failure syndrome, while a decrease in the severity of endotoxicosis and post-ischemic lesions was noted, both according to clinical laboratory and encephalographic indicators.

In recent years, natural AO – thioctic (lipoic) acid – has been actively studied. Thioctic acid is necessary for the regeneration and restoration of vitamin E, the vitamin C cycle and the generation of Q_enzyme (ubiquinone), which are the most important parts of the body's antioxidant defense. In addition, thioctic acid can interact with other compounds, restoring the AO pool in the body. Thioctic acid facilitates the conversion of lactic acid into pyruvic acid with its subsequent decarboxylation, which helps eliminate metabolic acidosis. A positive lipotropic effect of thioctic acid was noted. The uniqueness of the chemical structure of ioctic acid allows its regeneration to be carried out independently, without the participation of other compounds. Ioctic acid plays a significant role in the process of energy formation in the body. This explains the widespread occurrence of lipoic acid in nature and its presence in animal cells (with the exception of the thyroid gland) and plant origin. The daily requirement of an adult for lipoic acid is 1–2 mg.

Thioctic acid is currently used in the form of its trometamol salt (thioctacid). A number of studies have shown the effectiveness of ioctacid in the treatment of diabetic and alcoholic polyneuropathy, Wernicke-type cephalopathy, acute ischemic and traumatic brain injury.

In case of critical neurological conditions, treatment with thioctacid should begin with intravenous infusions of 1 ampoule (600 mg of thioctic acid) diluted with 200 ml of saline per day for 2–3 weeks. Next, 600 mg thioctacid tablets are prescribed once in the morning, 30 minutes before breakfast. In severe cases of the disease, it is possible to use a daily dosage of 1800 mg of thioctacid per dose. The course of treatment is 1–2 months. Bligate alimentary AOs are represented by compounds of direct indirect action. AOs of direct action include vitamins E, A, C, K, carotenoids, ubiquinone and amino acids - cysteine and its derivatives, sulfur-containing betaine_ergothioneine. AOs of indirect action include itamins B2, PP, amino acids methionine and glutamic acid, trace elements selenium and zinc.

The main role of the listed dietary AOs is due to their functioning as part of the antioxidant system, which determines their use in many neurological diseases accompanied by excessive free radical oxidation. Considering the universality of the pathogenetic phenomenon of free radical oxidation and lipid peroxidation processes presented above, it is advisable to prescribe nutritional AOs after traumatic brain injuries, neuroinfections, and in asthenic conditions after acute respiratory and viral diseases. Nutritional AOs are recommended to be included in the complex treatment of the consequences of stroke, chronic cerebral ischemia, neurodegenerative diseases, exacerbations of multiple sclerosis, and epilepsy. Currently, various medicinal compositions containing AOs of direct and indirect action are widely represented on the pharmaceutical market. In addition, many AOs are included in various food supplements. Medicinal compositions and nutritional supplements allow the practitioner to choose a treatment regimen taking into account the individual pathogenetic factors of the disease identified in the patient.

The table shows the daily requirement for AO (vitamins and microelements) of the adult population (quoted by Goodman, Gilman. “The Pharmacological Basis of Therapeutics”).

Ivan Drozdov 13.04.2018

Neuroprotectors are a group of drugs that provide the protective function of the nervous system from adverse factors. Neuroprotectors include substances that ensure the functioning of the metabolic system, help maintain the integrity of nerve cells, protect them from death and improve oxygen supply. With their help, brain structures can quickly adapt to negative changes caused by pathological conditions such as senile dementia, Parkinson's syndrome and other neurological diseases.

Classification of drugs

Depending on the mechanism of action and composition, the following groups of neuroprotective drugs are distinguished:

Nootropics – improve the functioning of the metabolic system and are used in the treatment of neurological and mental disorders.
Antioxidants - designed to fight free radicals that appear under the influence of adverse factors.
Vasoactive (vascular) drugs – reduce vascular permeability, help improve blood circulation:

anticoagulants – reduce blood viscosity;
angioprotectors – increase blood microcirculation in the walls of blood vessels, thereby reducing their permeability;
myotropes – help increase vascular tone and blood flow through the vessels;
drugs that affect metabolism (calcium channel blockers);
psychostimulants – provide nutrition to the brain.

Combination drugs – combine several properties (for example, vasoactive and antioxidant).
Adaptogens are neuroprotective drugs of plant origin.

The described neuroprotectors, depending on the diagnosis and state of health, can be combined during administration, while the range of drugs, as well as the treatment regimen, must be determined by the doctor.

Nootropic drugs

Nootropics are drugs that activate the interaction between nerve cells in the brain. Their action is aimed at:

improving memory, concentration and thought processes;
relieving nervous overexcitation;
elimination of depressive mood;
increasing the body's resistance to negative factors;
improving blood supply to the brain;
prevention of epileptic seizures and manifestations of Parkinson's syndrome.

Cerebrolysin

The hydrolyzate isolated from the pig brain quickly penetrates the brain cells through the blood and prevents the development of tissue necrosis caused by pathological conditions such as stroke, Alzheimer's disease, dementia, encephalitis, etc. In case of circulatory failure in the acute period due to stroke, brain infections, traumatic brain injuries, the drug is prescribed intravenously by drip infusion, dissolving it in special infusion solutions. In a state of sluggish circulatory disorders, Cerebrolysin is administered intramuscularly, without allowing it to be mixed in the syringe with substances that affect the functioning of the heart and vitamins.

Piracetam

The drug helps to increase the concentration of adenosine triphosphoric acid (ATP) in brain cells, which in turn has a positive effect on the functioning of the vascular system, restoration of cognitive, cerebral and metabolic functions. The action of the drug is aimed at protecting brain cells from damage caused by oxygen deprivation, intoxication, injury, and exposure to electric current.

Cerakson

Citicoline, which is the main active ingredient of the drug, has a beneficial effect on the membranes of brain tissue, protecting them from damage caused by traumatic brain injuries and strokes. It increases the speed of energy impulses between nerve cells, helps restore memory, concentration, awareness and thinking. Cerakson promotes a speedy recovery from post-traumatic and post-stroke coma, as well as a reduction in the severity of neurological symptoms characteristic of pathological conditions.

Antioxidants

The action of antioxidant drugs is aimed at neutralizing free radicals that have a negative effect on nerve cells and the body as a whole. Pharmaceuticals are prescribed if the body is exposed to such unfavorable factors as poor climate and ecology, work in harmful conditions, metabolic and endocrine system disorders, heart and vascular diseases. Taking them can increase the resistance of brain tissue to hypoxia, maintain energy balance, reduce the impact of long-term alcohol intoxication on nerve cells, and prevent the development of senile dementia.

Glycine

An amino acid that regulates metabolic processes in the central nervous system. A drug with a sedative and anti-stress effect is prescribed for increased nervous excitability, emotional exhaustion, neuroses, vegetative-vascular dystonia, and ischemic stroke. The cumulative effect of taking Glycine allows you to improve blood circulation, reduce the manifestations of psycho-emotional fatigue, and increase performance.

Mexidol

A powerful antioxidant used for acute attacks of impaired blood supply to the brain - epileptic seizures. The drug is also indicated for use in cases of decreased performance, loss of strength, nervous overexcitation, neuroses, alcohol intoxication, atherosclerotic disorders, and slowed down thinking processes characteristic of senile dementia.

Glutamic acid

A dicarboxylic amino acid that stimulates the metabolic system and the interconnection of neurons in brain structures. It ensures the resistance of brain tissue to oxygen deficiency and protects them from intoxications of various types - alcohol, chemicals, medications. The drug in combination with other antipsychotics is prescribed for mental disorders - psychosis, epilepsy, schizophrenia, as well as brain infections - encephalitis, meningitis. In childhood, glutamic acid is used to treat cerebral palsy, Down's disease, and polio.

Vascular drugs (vasoactive)

Pharmacological agents that have a beneficial effect on blood vessels and hematopoietic function are prescribed to improve blood supply to brain tissue and metabolic processes between neurons. Depending on the mechanism of action, they are divided into several types:

myotropic antispasmodics – improve vascular tone and blood flow through them to brain structures;
drugs that improve metabolism between nerve cells;
angioprotectors;
drugs that nourish nerve cells;
anticoagulants.

Cinnarizine

Myotropic antispasmodic with vasodilating properties. Under its action, blood fluidity is normalized, blood circulation improves, the resistance of nerve cells to oxygen starvation increases, and the bioelectrical exchange between them is activated. The drug relieves vasospasm and the symptoms accompanying this condition (,). It is prescribed for ischemic stroke, senile dementia, memory loss, Meniere's disease.

Vinpocetine (Cavinton)

The drug, which has antiplatelet, antihypoxic and vasodilating properties, accelerates metabolism in brain tissue, improves blood flow and oxygen delivery to them. Thanks to this, its use is effective in the acute stage of stroke, as well as in the progression of senile dementia. Taking Vinpocetine helps reduce the impact of neurological symptoms, improve memory, increase concentration and intellectual abilities.

Acetylsalicylic acid

An anti-inflammatory drug with antiplatelet properties. Taking it in large quantities helps suppress the biosynthesis process in platelets, due to which the blood clotting process slows down. Preparations containing acetylsalicylic acid are used in the post-stroke period to prevent the formation of blood clots.

Heparin

An anticoagulant with an effect aimed at preventing and treating diseases associated with the formation of blood clots - thrombophlebitis, thrombosis. The drug thins the blood and is administered intravenously in individual dosages. Contraindications to its use are bleeding disorders, the postoperative period, and gastrointestinal ulcers.

Combination drugs

Neuroprotectors of combined action have several properties that enhance each other, which makes it possible to achieve faster and more effective results in treatment by taking low doses of active substances.

Fezam

A drug based on Cinnarizine and Piracetam is prescribed to dilate blood vessels, increase the resistance of brain tissue and nerve cells to a lack of oxygen, and stimulate blood flow to areas of the brain that have been subject to ischemia. Phezam is also used to restore memory and thinking, improve emotional mood, eliminate intoxication syndrome and loss of strength.

Thiocetam

The drug is based on two main pharmaceutical agents - Thiotriazolin and Piracetam. Indications for the use of Thiocetam are cerebrovascular accidents and disorders caused by them, vascular diseases, brain, heart and liver diseases, as well as viral infections. Taking the drug helps strengthen the immune system and increase the resistance of brain cells to hypoxia.

Orocetam

A combined nootropic drug based on Piracetam and orotic acid improves liver function and its detoxification functions, accelerates the exchange of impulses between nerve cells. Thanks to these properties, Orocetam is effectively used for severe brain intoxication caused by infectious diseases and viruses, as well as alcohol and chemical poisoning.

Adaptogens

Herbal preparations that increase the body's resistance to harmful and pathological influences are called adaptogens. Substances in herbal remedies help adapt to stress and sudden climate change. They are effectively used during the recovery period for the treatment of infectious diseases of the brain, and intracranial injuries.

Ginseng tincture

The herbal product has a beneficial effect on the nervous, vascular and metabolic systems. It is prescribed as an adjuvant therapy for patients weakened by the disease, as well as in the presence of signs of physical and nervous exhaustion. Taking the infusion helps lower blood sugar, increase blood pressure during hypotension, improve metabolism, and eliminate bouts of vomiting.

Ginkgo biloba

The drug contains plant substances such as eleutherococcus and gotu kola. It is prescribed for intracranial hypertension, decreased brain function, nervous fatigue, vascular and endocrine diseases, and decreased transmission of impulses between nerve cells.

Apilak

A biostimulant based on dried royal jelly of bees is prescribed for low blood pressure, loss of strength, eating disorders, mental and neurological disorders. Apilak is not recommended for use in cases of adrenal dysfunction, as well as hypersensitivity or intolerance to bee products.

Indications and contraindications for the use of neuroprotectors

The action of neuroprotectors is aimed at improving metabolic processes between brain cells and their adaptation to changes caused by circulatory disorders. Their use is indicated for the following pathological conditions:

Taking neuroprotectors is contraindicated in the following cases:

hypersensitivity to substances included in the drug;
inflammatory and infectious processes occurring in the kidneys and liver;
when taking other sedatives and antidepressants;
heart failure;
pregnancy and lactation period.

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Neuroprotective drugs should also be discontinued if the patient experiences side effects after taking them - nausea, vomiting, allergic rash, increased breathing and heart rate, nervous overexcitation.