Introduction. Alcohol intoxication is often the cause of traumatic brain injury. The purpose of the work was to study the features of lipid metabolism in erythrocytes and mitochondria of the cerebral cortex cell membranes of rats in traumatic brain injury on the background of chronic alcohol intoxication. Materials and methods. The studies were carried out on 140 male rats of the Wistar line weighing 170-250 g. Chronic alcohol intoxication was caused by using 15% ethanol as the only source of fluid for 20 days. Reproduction of traumatic brain injury was carried out by a shock model. Statistical analysis of data was conducted by using „Primer Biostatistics 6.0”. The criteria of parametric statistics were used. The level of p <0.05 was statistically significant. Results. Chronic alcohol intoxication in rats and inducing of traumatic brain injury separately causes a significant change of total phospholipids and cholesterol content, and their molar ratio in the membranes of erythrocytes and mitochondria of the cerebral cortex. Particularly pronounced were the changes in studied objects with combined pathology, meaning, traumatic brain injury on the background of chronic alcohol intoxication. Discoordination of lipid metabolism was unidirectional, manifested in a significant reduction in the content of total phospholipids, and increased total cholesterol, which led to a violation of the molar ratio of total cholesterol/phospholipids in the direction of increasing the coefficient, which is normally about 1.0. In subsequent monitoring periods, there was a gradual restoration of individual fractions of phospholipids, but on the 30th day of the study, it did not reach the control values. That means that discoordination of the metabolism of individual phospholipid fractions was so pronounced, that even on 30th day of arbitrary reproduction did not reach the initial values, which again emphasizes the severity of the morphofunctional state of red blood cells membranes’ disturbance. Conclusions. The revealed features of lipid metabolism in the membranes of erythrocytes and mitochondria of the cerebral cortex in traumatic brain injury on the background of chronic alcohol intoxication are an important component for understanding the ongoing pathophysiological processes and searching for new effective drugs with targeted action.

Objective: One of the primary reactions of the genome in response to stress is different genesis induction of heat shock proteins - HSP. The purpose of this study was to investigate the concentration of heat shock protein (HSP70) and hypoxia-inducible factor (HIF-1) in the brain of rats undergoing chronic prenatal alcoholism in different periods of ischemia and define the role of these proteins in the implementation of neuroprotective effect of Cerebrocurin and Tiocetam.Methods: Experiments were carried out on female rats weighing 150-180 g. All animals were on standard food ration of vivarium, with natural alteration of day and night. Rats were recieved from nursery of "Institute of Pharmacology and Toxicology, Academy of Medical Sciences of Ukraine". All experimental procedures and operative interventions were done in accordance with WMA Statement on Animal Use in Biomedical Research. Rats from the 5th to the 20th day of gestation received ethanol in a dose of 6-8 g/kg/day, control rats - isocalorific sucrose solution. Offspring of alcoholized rats immediately after birth during 25 days were injected intraperitoneally Tiocetam (125 mg/kg), Piracetam (125 mg/kg) and Cerebrocurin (0.06 mg/kg), control rats received saline solution. There were 20 infants in each group. Biochemical studies carried out on brain on 26 days of the experiment, for this purpose the animals were decapitated under anesthesia using Thiopental (30 mg/kg, intraperitoneally). Concentration in the brain tissue and HIF proteins and HSP proteins were determined by Western blot analysis.Results: Study of concentration in brain tissue HIF proteins and HSP-proteins showed that after undergoing prenatal chronic alcoholism there was an observed decrease in concentration of HSP, so HIF-proteins. Course treatment by Cerebrocurin and Tiocetam resulted in statistically significant increased content of HIF and HSP proteins in the brain in comparison with a group of untreated animals. Neuroprotective activity of Cerebrocurin and Tiocetam was observed in reduction of neurological deficit, as evidenced by the statistically significant decrease in the average score on a scale of C.P. McGrow. Cerebrocurin and Tiocetam directly or indirectly can modulate the expression of early response c-fos genes and thus the "run" software adaptation protein synthesis (including HSP and HIF) in neurons with acute cerebral ischemia.Conclusion: Implementation of the neuroprotective effect of Cerebrocurin and Tiocetam revealed apparently their ability to increase the concentration in the brain tissues of HSP-protein.

The studies have shown that drinking alcohol by woman during pregnancy can lead not only to a full fetal alcohol syndrome, but also causes less severe dysmorphic, cognitive and behavioral disordersl, i.e. fetal alcohol spectrum disorders, leads to low birth weight, fetal death, and other complications of pregnancy. The purpose of this study was to investigate the influence of neuroprotective drugs tiocetam, cerebrocurin and piracetam on the marks of thin elements of energy metabolism and compensatory shunts in the brain of animals early age undergoing prenatal alcoholism. In pregnant rats with alcoholism were found neuroprotective and nootropic effects of cerebrocurin and tiocetam after parenterally administered to newborn animals for a period of 25 days. The above drugs have a beneficial effect on the main elements of the energy metabolism on the neonatal brain. On the severity of mitoprotective and energotropic mechanisms of neuroprotective action, aimed at reducing the negative impact of alcohol on the progeny, tiocetam and cerebrocurin far exceed basic nootropic drug piracetam.

Our research found that prenatal alcoholism leads to increase of NO induction and nitrosine stress in the brain of newborn rats, evidenced by the increasing of nitrotyrosine in citosole and mitochondria. By adjusting the ratio of mitochondrial/cytosole concentrations of NO and reactive oxygen forms, cerebrocurin and tiocetam limited the effect of these compounds on the activation or deprivation of the processes of gene expression, transcription and translation in neuronal cells of brain of animals that survived the prenatal alcoholism and, thus, may provide the normal development of the cognitive functions of central nervous system. And increased expression of the protein bcl-2 in the group of animals receiving cerebrocurin and tiocetam, testifies to the activation of antiapoptosis protection of damaged neurons. © 2014 Elixir All rights reserved. ARTICLE INF O Articl e h istory: Received: 22 April 2013; Received in revised form: 29 September 2014; Accepted: 23 October 2014;

Patients with chronic alcohol intoxication have diffuse changes extended on all nervous system and local defeat (parenchymal disintegration, gliosis hems, haemorrhage). Research on new ways of pharmacocorrection of morphofunctional changes in neuro-glial structures of the brain and restoration of interneural interactions at modelling of 30-day chronic alcoholic intoxication in rats, has defined effective neuropeptide cerebroprotectors (cerebrolisin, cоrtexin and cerebrocurin). Also, results of experiment have shown that the most active preparation is cerebrocurin, so it is recommended for inclusion in the traditional scheme in treatment of chronic alcoholic intoxication.

Острая или хроническая ишемия мозговой ткани обуславливает целый каскад патобиохимических реакций, которые в конечном итоге приводят к развитию очагового неврологического дефицита, дисциркуляторной энцефалопатии или к гибели больного. В различные сроки ишемии (1 ч, 6 ч, 24 ч, 48 ч, 72 ч, 120 ч и 21 сут) установлено, что в период наибольших ишемических нарушений (24–72 ч) наблюдается гиперпродукция лактата на фоне угнетения гексокиназы (ГК) – фермента, катализирующего первую “пусковую” реакцию гликолиза. Рост малата с повышением активности митохондриальной (мМДГ) и цитозольной (цМДГ) малатдегидрогеназ в первые часы церебральной ишемии свидетельствует об активации малат-аспартатного челночного механизма транспорта восстановленных эквивалентов в митохондрии. Угнетение продукции малата и активности НАД-зависимой малатдегидрогеназы (НАД-МДГ-мх) коррелирует с падением АТФ, HSP-70 и фактора, индуцируемого гипоксией (HIF-1a), а также со степенью неврологических нарушений. Можно предположить, что в ответ на формирование ишемии головного мозга экспрессируется HIF-1a, который инициирует запуск компенсаторных механизмов выработки энергии. В дальнейшем регуляция этих процессов переключается на HSP-70, который “пролонгирует” действие HIF-1a, а также самостоятельно поддерживает экспрессию активности НАД-МДГ-мх, тем самым длительно поддерживая активность малат-аспартатного челночного механизма.

Acute or chronic brain ischemia induces a cascade of pathobiochemical reactions that finally result in the development of focal neurological deficit, dyscirculatory encephalopathy, or the death of a patient. We studied the effects of ischemia at different time points, including 1, 6, 24, 48, 72, and 120 h, and 21 days. During the period of the strongest ischemia-induced disturbances (24–72 h), we found lactate over-production associated with inhibition of hexokinase, an enzyme that catalyzes the first “trigger” reaction of glycolysis. An increase in the malate content associated with increasing activities of mitochondrial and cytosolic malate dehydrogenases within the first hours of cerebral ischemia indicates the activation of the malateaspartate shuttle, which is responsible for the transportation of reduced equivalents to mitochondria. The inhibition of malate production and activity of NAD-dependent malate dehydrogenase correlates with a decrease in the contents of ATP, HSP70, and hypoxia-induced factor-1a (HIF-1a) and the severity of neurological disturbances. We believe that in response to brain ischemia, HIF-1a is expressed, which induces compensatory mechanisms of energy production.

The modeling of chronic alcohol intoxication for 30 days in rats leads to an increase in the level of free metabolites of nitrogen oxide and NO-synthase with simultaneous decrease in the levels of L-arginine, catalase, and superoxide dismutase. The subsequent 14-day treatment with neuropeptide cerebroprotectors cerebrocurin, cortexin, and cerebrolysin led to normalization of the parameters of nitrogen oxide system. The maximum therapeutic activity was shown by cerebrocurin, which can be recommended for inclusion as component of alcoholic encephalopathy treatment.

We studied the involvement of HSP70 and Hif1b genes in the development of pathological changes in the brains of experimental animals during ischemia. We found neuro- and mitoprotective characteristics of heat shock protein HSP70 and Hif1b in vitro and under cerebral ischemia due to stabilization of molecules damaged by oxidation, inhibition of nitrosative and oxidative stress and mitoprotective action directed to amelioration of mitochondrial dysfuction. The protective role of these proteins provides a new direction for the development of novel neuroprotective drugs that protect or modulate the genes that encode these proteins.

Experimental chronic alcoholism in rats and pathogenetic aspects of energy metabolism change are shown in the article. For normalization of processes of energy state neuropeptide cerebroprotectors cerebrolisin, cortexin and cerebrocurin are offered in the scheme of complex neuroprotective therapy. According to the results of biochemical research of rats brain homogenate cerebrocurin revealed to be the most effective.