An analysis of modern methods of surgical and conservative treatment of brain bruises, taking into account the concept of primary and secondary brain damage.
Treatment of brain bruises
Information for specialists in the field of medicine, pharmacy and health care!
A.E. Talypov, Ph.D., S.S. Petrikov, D.M., Professor, Yu.V. Prasse, Ph.D., A.A. Malt, Ph.D., Yu.V. Titova, Ph.D.,
NIISP them. N.V. Sklifosovsky, Moscow
An analysis of modern methods of surgical and conservative treatment of brain bruises, taking into account the concept of primary and secondary brain damage.
Card-brain injury (CHMT) is one of the most common types of damage. In the overall structure of injuries to the share of CHMT accounts for about 40%. The Frequency of CHMT in Russia is from 1.6 to 7.2 cases per 1,000 population per year, i.e. more than 600 thousand people per year. [nineteen]. And it is the leading cause of death and disability among the population under 45 years old. The number of persons with disabilities after the TWT in the United States is 3 million people, in Russia more than 2 million patients with a concussion of the brain constitute half of all patients with CMT. The fraction of patients with brain injury accounts for 30%, and in 20% detect traumatic intracranial hematomas. In the neurosurgical hospitals of Moscow annually hospitalize 3.5-4 thousand patients with a brain injury of varying severity, more than 2,000 patients with squeezing by traumatic hematomas. More than 500 victims with a cranial trauma conduct surgical treatment. Half of the victims of the CHHMT are observed the consequences of various degrees of severity – from functional disorders to coarse neurological symptoms. With severe brain injury, there may be a vegetative state or a minimum consciousness syndrome. The brain injury is a risk factor for the development of Alzheimer's disease and Parkinsonism in the remote CMT period. During the first year after the first year, the probability of developing an epileptic attack is 12 times higher than in the overall population. Post-traumatic epilepsy is detected in 13% of patients who have suffered a brain injury to medium severity.
Pathophysiology CHMT
Brain damage due to CMT is divided into primary and secondary (Fig. 1). Primary damage is due to the impact of the traumatic force on the skull bones, the shell and brain fabric, brain vessels and the liquor system. The primary damages are referred to as well. And the foci of brain bruises, primary bruises of the brain, diffuse axonal and vascular brain damage. In primary damage, there is a violation of the structure of neurons and glial cells, synaptic breaks are formed, vessel thrombosis occurs and the integrity of the vascular wall is disturbed. The consequence of the primary injury is to reduce access of adenosine trifhosphate (ATP) and violation of the permeability of the cell membrane ("membrane pump"), which leads to the death of the cell or cytotoxic edema.
A perifocal zone is formed around the focus of primary damage, in which cells retain their viability, but become extremely sensitive to the slightest changes in the delivery of oxygen and nutrients (the penumbra zone).
Secondary (ischemic) brain damage. In response to primary damage, a pathological process occurs, which is an evolutionarily developed inflammatory response. These changes are bidirectional, i.e. they cause both damage to cell structures and are neuroprotective in nature.
Immediately after injury, neuronal metabolism increases, which is accompanied by ATP depletion, dysfunction of the transmembrane calcium pump, increased permeability of cell membranes for calcium ions, calcium release from intracellular depots, which causes depolarization of nerve endings and the release of “excitatory” neurotransmitters (glutamate) from them, which leads to damage to the membranes of neurons and the endothelium of the brain capillaries (excitotoxicity). Glutamate, by activating postsynaptic complexes, causes an influx of sodium ions into the cell, depolarization, and an even greater influx of calcium ions through ion channels. The consequence of cell overload with calcium is its damage caused by the activation of phospholipases, proteases and nucleases, leading to disruption of the integrity of cell membranes, phosphorylation and protein synthesis and genome expression, and lysis of the structural proteins of the cell.
The death of neurons in TBI also occurs due to apoptosis. Apoptosis can be triggered both by the direct action of a traumatic agent on the cell genome, and indirectly by the damaging action of inflammatory mediators. The consequence of the action of factors of secondary brain damage is a violation of the delivery of oxygen and nutrients to the brain cells and their insufficient utilization. Particularly affected are cells located close to the focus of primary brain damage (the penumbra zone). There are violations of cerebral microcirculation, oxygenation and metabolism of neurons, cerebral edema and its ischemia develop. Secondary ischemic brain damage occurs in 36–42.6% of patients with moderate TBI and in 81–86.4% of patients with severe TBI. The development of secondary brain damage significantly aggravates the severity of the condition of patients with TBI, impairs the recovery of mental and motor activity of patients, and increases the risk of developing an unfavorable outcome. In this regard, the prevention and timely correction of factors of secondary brain damage is the most important task in the treatment of patients with severe TBI [1, 9].
Classification of brain contusions
According to the classification of trauma adopted in the Russian Federation according to the clinical course and severity of damage to the brain tissue, brain contusions are divided into mild, moderate and severe contusions.Also allocate special forms of brain injury: diffuse axonial damage (dap) and traumatic subarachnoid hemorrhage [9].
Most often occurs the injury of the brain of medium severity of 49%, the injury of a light degree is detected in 33% and injury in 18% of patients. The criteria for determining the severity of the branch of the brain is the degree of violation of the wakefulness, the severity of the state of the patient, the severity of neurological symptoms and data of the instrumental diagnostic methods (CT and MRI of the brain, data of laboratory research methods).
The injury of the brain is easy to characterize the rapid restoration of wakefulness after its primary loss, which lasts within a few minutes. In the clinical picture, general-level symptoms prevails: headache, nausea, vomiting, dizziness, weakening of attention, memory. Nistagm may be detected (more often horizontal), anisaneflexia, sometimes light hemiparesis. With lumbar puncture in the cerebrospinal fluid (CSW), an admixture of erythrocytes is possible. The brain's bruises of a light degree can be accompanied by fractures of the bones of the skull, but they may occur without them. 40-50% of patients on CT are detected by foci of low density – sections of ischemia edema density from 18 to 28 units. N. With histological examination of such foci, salted brain fabric detects, can be broken of small vessels, dot diapered hemorrhages. The regression of these morphological changes occurs within 2-3 weeks.
Middle severity brain injury is characterized by loss of wakefulness from several tens of minutes to 2-4 hours. The degree of wakefulness is reduced to a level of moderate or deep stunning and stored for several hours or days. Common-based symptoms are pronounced. The medium severity characteristic of the height brain characteristic is the presence of traumatic subarachnoid hemorrhage. Meningleal syndrome is moderately expressed, and the pressure of the CSC is moderately increased (with the exception of victims, which have Likvorea). Part of patients may have focal neurological symptoms: moderately pronounced hemiparesis and pathological reflexes, sensitivity disorders, aphasia. Breathing disorders in the form of a moderate tachipne without a rhythm disturbance and do not require hardware correction. On craniograms in most patients (62%), the skull fractures are detected, of which in 35% – the crop fractures, in 50% of the base and in 15% are fractures of the arch and base of the skull.
The CT is determined by the foci of the brain's injury. Perifocal swelling usually does not further apply to one share of the brain. Typically, patients with a bruise of the brain of moderate severity do not require surgical treatment, except for the skull suffered with indulged fractures.
Heavy degree brain injury.With this type of damage, the decrease in the degree of wakefulness to stupor or coma lasts from several hours to several days, in some patients with a transition to apallic syndrome or akinetic mutism. Stem symptoms are characteristic, sometimes hormetonia develops – to painful stimuli or spontaneously, bilateral pathological foot reflexes, changes in muscle tone are determined. Violations of vital functions (respiration and circulation) in most cases require correction. On craniograms, fractures of the vault, base or vault and base of the skull are detected in almost all victims. On CT, there are foci of brain contusion of various sizes, accompanied by perifocal or widespread edema of the brain tissue. Pathological anatomical examination reveals foci of brain destruction over a considerable extent both on the surface and in depth. The volume of detritus may be equal to or greater than the number of blood clots
A special form of brain contusion is diffuse axonal injury of the brain (DAI). Taking into account the pathophysiology of the development of brain damage – due to acceleration / deceleration and the rotational component, the displacement of gray and white matter relative to each other, which have different densities, and the rupture of axonal connections as a result, disturbances in the axonoplasmic current – a clinical picture of brain stem damage develops – depression of consciousness to a deep coma, violation of vital functions that require mandatory medical and hardware correction. A decrease in the degree of wakefulness is a characteristic clinical sign of DAD, and in 25% of victims, the duration of loss of consciousness exceeds 2 weeks. Mortality in brain DAP is very high, reaching 80–90%, and most survivors develop apallic syndrome. DAP can occur both independently and be accompanied by the formation of intracranial hematomas.
Treatment of brain bruises
Over the past 30 years, the strategy for the treatment of brain contusions has been aimed at adequate surgical treatment of primary contusion foci and conservative treatment aimed at the cascade of secondary brain injuries using modern methods of neuroimaging and neuromonitoring. 10–15% of patients with brain contusion undergo surgical treatment (Fig. 1).
It should be taken into account that in 20% of the victims, traumatic intracranial hematomas are combined with foci of brain contusion, which are removed during surgery. Surgical treatment of brain contusions should be carried out with the development of brain compression, intracranial hypertension and brain dislocation. Indications for surgical treatment of focal contusions of the brain are:
1. The presence of foci of contusion-crushing of the brain, causing a progressive deterioration in the neurological status, persistent intracranial hypertension, refractory to intensive care, or in the presence of signs of a mass effect.
2.Reducing the degree of wakefulness to a copor or coma at the volume of the focus in the frontal or temporal share of more than 20 cm3, if the displacement of the median structures> 5 mm and there is a deformation of the covering tank.
3. The volume of the lesion focus is more than 30 cm3 (the diameter of intracerebral hematoma is more than 4 cm).
Depending on the volume, the localization of the borders of the brain injections use various methods of treatment (Fig. 2). The monitoring of intracranial pressure is necessary in the treatment of patients with a severe brain injury, which are in comatose state with clinical signs of intracranial hypertension. To measure the HBD in the brain substance, a ventricular or parenchymal sensor connected to the monitor is installed. Indications for surgical treatment of victims with diffuse brain injury serves as a persistent increase in the VCHB over 25 mm RT. Art., Refractory for conservative therapy. In this case, the decompressive bifrontal trepanation of the skull is performed.
Mortality in patients operated on about the brain's injury is 40%. A good outcome occurs in 20% and the disability of varying degrees – in 40% of patients (Fig. 3). The outcome of surgical treatment depends on the degree of wakefulness of the patient before surgery. A good outcome of treatment is possible only in patients with a degree of wakefulness not lower than the spin.
Conservative brain injury therapy
The most important tasks of intensive therapy of victims with severe CMT (including and in the postoperative period) is the prevention and treatment of secondary brain damage, including secondary brain ischemia, and neuroprotection, which reduces the impact of secondary damaging factors and allows nerve cells Avoid death. Pathophysiology of CMT is extremely complex and diverse and affects not only the brain, but also many different systems and tissues. Experimental studies have shown: therapy aimed at preventing necrosis of nerve cells may increase cell apoptosis [10]. Thus, in the treatment of patients with CHF to prevent the development of secondary damage to the brain, it is necessary to influence various tracks of pathogenesis.
The main directions of conservative therapy of victims with the injuries of a severe brain are:
• respiratory support;
• Correction of hemodynamics and infusion therapy;
• diagnostics and correction of intracranial hypertension;
• Neuroprotection.
Respiratory support. Indications to carry out the intubation of trachea and respiratory support among victims with severe CMT are:
oppression of the level of wakefulness of up to 10 points and less than a shkg;
Lack of self-breathing (apnea);
acutely developed respiratory rhythm violations, pathological rhythms, agonal type respiration;
Tahipot more than 30 per minute, not associated with hyperthermia or severely displeased hypovolemia;
clinical signs of hypoxemia and/or hypercapnia (PaO2 less than 60 mm Hg, SaO2 less than 90%, PaCO2 more than 55 mm Hg);
status epilepticus
Thus, the indication for tracheal intubation and artificial lung ventilation is not only respiratory, but also cerebral insufficiency.
The main task of respiratory support is to maintain relative normocapnia (PaCO2 – 33-40 mm Hg) and sufficient oxygenation of arterial blood (PaO2 more than 100 mm Hg). With intact lungs, the tidal volume should be 8-10 ml per kg of ideal body weight. If prolonged mechanical ventilation is necessary, a tracheostomy should be performed within 48 hours after the start of respiratory support. The choice of the mode of respiratory support is carried out individually. As a rule, in the process of respiratory therapy, a periodic change in ventilation modes is carried out, selecting them according to the needs of the patient.
Correction of hemodynamics and infusion therapy. Infusion therapy is one of the main methods of intensive care for patients with severe traumatic brain injury. More than half of the victims with depression of consciousness to stupor and coma upon admission to the intensive care unit are in a state of hypovolemia. The cause of hypovolemia is most often blood loss, insufficient fluid intake, elevated body temperature, vomiting, diabetes insipidus. Conducting adequate infusion therapy allows achieving normovolemia, normalizing cardiac output and oxygen delivery to the affected brain. Rapid correction of the volemic status prevents the development of a significant amount of secondary ischemic brain damage and is accompanied by a decrease in mortality. To accurately determine the volemic status, methods for assessing systemic hemodynamics (transpulmonary thermodilution, transesophageal dopplerography, etc.) should be used. It is advisable to use invasive blood pressure monitoring. The parameters commonly used by the doctor – mean arterial pressure (MAP), heart rate (HR) and central venous pressure (CVP) – have low sensitivity and do not reflect the severity of hypovolemia. To ensure sufficient cerebral perfusion, it is necessary to maintain cerebral perfusion pressure (CPP) within 60-70 mm Hg. Art. and prevent the development of arterial hypotension (decrease in systolic blood pressure to 90 mm Hg or less). For individual selection of CPP, cerebral oxygenation and metabolism are monitored (saturation in the bulb of the jugular vein, oxygen tension in the brain substance, tissue microdialysis). The composition of infusion therapy should include modern colloidal preparations, and for individual selection of the volume and structure of infusion therapy, systemic hemodynamic monitoring should be used.When calculating the volume of infusion therapy, the physiological need for fluid (30-40 ml / kg / day), as well as additional factors affecting water metabolism, should be taken into account.
Diagnosis and correction of intracranial hypertension. For rapid diagnosis and timely treatment of intracranial hypertension (ICH) syndrome, all victims with depression of the level of wakefulness up to 8 or less GCS points should monitor intracranial pressure (ICP).
Allocate basic (prophylactic) and emergency therapy for intracranial hypertension (ICH).
Basic therapy is aimed at preventing and eliminating factors that can worsen or accelerate the development of ICH. To optimize the venous outflow from the cranial cavity, the head end of the patient's bed is raised by 30-40o, and the head is placed in the middle position. To reduce intrathoracic pressure and synchronize the respirator with the patient, the airway is patency, ventilation parameters are selected, and, if necessary, sedatives and muscle relaxants are used. An important component of therapy is the correction of hyperthermia, which is carried out with the help of antipyretic drugs and / or physical cooling methods.
emergency therapy. An indication for starting emergency therapeutic measures to correct intracranial hypertension is an increase in ICP to 21 mm Hg. Art. and more. Use a "step by step" algorithm to reduce ICP:
1. Computed tomography of the brain is performed to exclude the causes of ICH that require surgical correction.
2. In the presence of an intraventricular catheter, a controlled discharge of CSF is established, which is an emergency measure for correcting ICH.
3. Apply hyperventilation as a temporary measure to reduce elevated ICP. When using hyperventilation, the sufficiency of oxygen supply to the brain should be monitored by determining SvjO2 and / or PbrO2.
4. Infusion of hyperosmolar solutions is carried out. A bolus injection of a 15% solution of Mannitol at a dose of 0.25-1.0 g/kg of body weight or HyperHAES at a dose of 2-4 ml/kg is used. Contraindications to the administration of hyperosmolar solutions are plasma osmolality of more than 319 mOsm/kg and/or hypernatremia of 159 mmol/l or more.
5. In the presence of refractory ICH, a medical coma is used. For drug-induced coma, sodium thiopental is most often used (induction – 30-40 mg / kg + infusion – 4-8 mg / kg / h).
6. Perform artificial hypothermia. Use modes of moderate hypothermia (body temperature 33-35oC).
7. If conservative measures are ineffective, decompressive craniotomy is performed.
Neuroprotection. Along with intensive therapy for TBI, neuroprotection is of great importance. Over the past decades, numerous clinical trials of various neuroprotective drugs and techniques have been carried out.Currently, more than 130 drugs or treatments have shown some efficacy in the treatment of traumatic brain injury in the experiment and in animal studies [11]. However, most of the studies conducted are ambiguous about the effectiveness of these drugs. The effectiveness of the use of corticosteroids, barbiturates, calcium channel blockers, free radical oxidizers, and glutamate antagonists in TBI has not been confirmed [12, 13]. The main reason for the relatively small progress in this direction lies in the complexity and versatility of the mechanisms of TBI pathogenesis. The speed of the course of pathological processes is also important, leading to a very short "therapeutic window" – the time during which the use of the drug is effective. The particular difficulty in correctly evaluating the effectiveness of drugs is determined by the large heterogeneity of patients by sex, age, comorbidities, the difficulty of conducting clinical trials and their evaluation, understanding both the mechanism of the pharmacokinetics of drugs and the mechanisms of development of secondary damage [14, 15, 16].
A large number of pathological mechanisms of secondary brain damage leads to the difficulty of choosing a particular drug, and any treatment strategy that prioritizes the use of a particular drug or technique is doomed to failure. Only a few of them are currently considered the most promising in the treatment of TBI.
Erythropoietin is a physiological hematopoietic factor that activates mitosis and maturation of erythrocytes from progenitor cells. Importantly, Erythropoietin is approved for clinical use and is widely used in patients with chronic anemia associated with kidney disease, cancer, and HIV infection. Recent studies [17] have shown the possibility of reducing mortality and improving functional outcomes in patients with TBI. The amount of erythropoietin and its receptors in healthy brain tissue is small, but their amount begins to increase in response to tissue damage. The neuroperative effect of erythropoietin is to inhibit apoptosis, anti-inflammatory activity, reduce the severity of angiospasm and improve cerebral blood flow. As a positive quality, it should be noted a small number of side effects (erythropoietin slightly increases the risk of venous thrombosis) and the effect in the subacute phase of TBI, which consists in stimulating the processes of neuro- and angiogenesis.
Progesterone is a steroid hormone, which is the main hormone of the corpus luteum, which is also produced in men in the adrenal cortex and is a precursor in the synthesis of glucocorticoids. Progesterone receptors are abundant in the central nervous system and are involved in the process of neuronal differentiation during embryonic development [18].In TBI, progesterone prevents damage to the blood-brain barrier, reduces the severity of vasogenic and cytostatic cerebral edema, reduces the concentration of free radicals and products of lipid peroxidation, inhibits apoptosis, inhibits the growth of the inflammatory response and the synthesis of pro-inflammatory cytokines in response to brain damage.
Statins are coenzymes of reductase inhibitors that inhibit cholesterol synthesis. Conducted preclinical and clinical studies have shown that in the acute stage of TBI, statins exhibit an anti-inflammatory effect that reduces the development of cerebral edema and ICH, and have a neuroprotective effect by reducing inflammation. Statins also regulate the level of endothelial nitric oxide synthase (eNOS) and stabilize the surface of the endothelium of cerebral vessels, which leads to improved brain perfusion [19]. In the subacute period of TBI, statins stimulate angiogenesis and neurogenesis.
Among the drugs used as neuroprotectors, citicoline occupies a special place. Citicoline (cytidine-5'-diphosphocholine), developed in 1967, is a compound consisting of ribose, cytosine, pyrophosphate, and choline. Citicoline is an endogenous substance, an intermediate metabolite of the Kennedy cycle – the biosynthesis of phosphatidylcholine, a structural component of neuronal membranes, necessary to maintain and restore its integrity. The participation of citicoline in the synthesis of sphingolipids, which are components of neuronal membranes, the effect on the level of various neurotransmitters, in particular acetylcholine, glutamate, a number of catecholamines (dopamine, serotonin, norepinephrine), has been shown.
One of the effects of citicoline in the acute period of TBI is a decrease in the level of free fatty acids and a decrease in the destruction of cell membranes due to the induction of phosphatidylcholine synthesis. By enhancing the function of membrane receptors and ion exchangers of the plasma membrane, citicoline reduces the degree of cerebral edema. In experimental models of cerebral edema, citicoline restored Na+/K+-ATPase activity by converting citicoline to membrane phosphatidylcholine. Citicoline improves cerebral blood flow and metabolism, stimulates the ascending reticular formation, pyramidal and extrapyramidal pathways, and thereby improves recovery from mental disorders and neurological disorders. This is due to an increase in the synthesis of phosphatidylcholine, a decrease in the level of free fatty acids, and an increase in the release of acetylcholine in the dorsal nuclei of the hippocampus, which was shown in an experiment on rats with experimental traumatic brain damage. It is also assumed that citicoline reduces lipid peroxidation, the formation of free radicals and lactate, restores the activity of Na + / K + -ATPase, stabilizes nerve cell membranes, and inhibits apoptosis.(repeat the beginning of the paragraph) Citicoline is one of the few drugs that has been shown to be effective in the treatment of traumatic brain injury and its consequences.
The effectiveness of citicoline in the treatment of patients with traumatic brain injury was shown in a study conducted at the NIISP them. N.V. Sklifosovsky prospective study, the purpose of which was to evaluate the efficacy and safety of the use of citicoline (Ceraxon®) in patients with mild to moderate brain contusion.
The study was conducted on the basis of an analysis of the results of clinical and instrumental studies of 58 patients with mild to moderate brain contusions. Patients received conservative therapy. The study was prospective, randomized.
Patients were included in the study according to the following criteria:
• Patients with mild to moderate brain contusions (focal brain contusions, traumatic subarachnoid hemorrhage (SAH), a combination of brain contusion and meningeal hematoma that did not cause brain compression);
• Age of patients from 18 to 60 years;
• First 48 hours after injury;
• Planned or ongoing therapy with Ceraxon® (in accordance with the instructions for medical use).
Criteria excluding participation in the program.
• Severe concomitant and (or) combined injury.
• The degree of wakefulness at admission is below 10 on the Glasgow Coma Scale (GCS).
• A history of severe allergic reactions to drugs.
• Severe somatic diseases, including cancer, chronic pulmonary, renal and hepatic insufficiency, pregnancy, lactation and chronic alcoholism.
• Introduction to patients of nootropic drugs (Cerebrolysin, Actovegin).
The main group included 28 patients who, along with the standard treatment provided for by medical economic standards (MES) for brain contusion, received Ceraxon® from Nycomed. During the first 7 days, Ceraxon® was injected intravenously at a dose of 300 mg dissolved in 200 ml of NaCL 0.9% twice a day. From the eighth to the fourteenth day, the drug was taken orally at 200 mg three times a day.
The control group included 30 patients who received standard therapy.
The duration of observation was 14 days for patients with mild brain contusion and 21 days for patients with moderate brain contusion. The standard therapy provided for by the MES standards included infusion and symptomatic therapy: analgesics, antiemetics, drugs that improve cerebral circulation. According to the indications, other drugs (antibiotics) were used. No nootropic or psychotropic agents, Ca2+ channel modulators, vasodilators, L-dopa preparations and dopamine antagonists, anticholinergics, glutamine modulators, diuretics were administered.
Patients conducted dynamic clinical, CT, EEG, laboratory studies. To estimate the effectiveness of the drug in a relatively short time during the treatment of patients with brain injuries, numerical scales were widely used, allowing to minimize subjectivism. Ceraxon® reliably accelerated the regression of general-year symptoms, including headaches and manifestations of astheno-vegetative syndrome.
The study of the brain reactivity using quantitative methods for analyzing the EEG in response to the use of the neuroprotector in the dynamics showed that the injuries of the brain are injured with light and moderate severity who received Ceurson®, the restoration of electrical activity was more successful. Among patients who received cyticoolin, not a single observation was revealed, in which the negative dynamics of EEG parameters would be observed. Positive dynamics was three times more often compared with the control group: in 70.0 and 23.3%, respectively.
The ratio of patients in whom there was no dynamics on the encephalogram, was inverse: in the control group of such observations it was significantly more (40.0 and 10.0%, respectively). The increase in the index of bilateral alpha-theta oscillations was noted in patients who received both cysticoline and standard therapy. However, in the latter, such patients were 33.3%, and among the victims who received Ceurson, 20.0%. A tangible decrease in the number of such observations in the main group allows us to conclude the effectiveness of the use of Ceurson® in the complex treatment of patients with acute CMT to prevent the development of post-traumatic complications of a paroxysmal nature.
Thus, the treatment strategy of patients with brain injuries is aimed at reducing the severity of the consequences of CMT, improving the functional outcomes due to the use of combined treatment that takes into account the pathogenesis of secondary damage. An important role in combination therapy is given to neuroprotection, which reduces the effect of secondary damaging factors and prevents the death of nerve cells. One of the few drugs with proven effectiveness in the treatment of the cranial injury is cysticoline, which reduces lipid peroxidation, the formation of free radicals and lactate, restores the activity of Na + / K + -atphase, stabilizes the membranes of nerve cells, inhibits apoptosis.