The thesis is dedicated to the experimental investigation of molecular biochemical mechanisms of glutoxim, selenase and glutaredoxin influence on energotropic and ROS links of ischemic neurodegeneration, and justification of their use as neuroprotective agents. According to the results of the research, mechanisms of neuroprotective action of selenase, glutoxim and glutaredoxin have been established. The research also examined and determined the mechanisms of selenase, glutoxim and glutaredoxin influence on the functional activity of mitochondria, and energy metabolism of the brain in the state of ischemia. It has been established that selenase, glutoxim and glutaredoxin inhibit the oxidative and nitrosative stress responses against the normalization of the glutathione system in the brain of test animals in the acute period of cerebral ischemia. For the very first time, this research provides the theoretical foundation and an experimental solution of the actual task of pharmacology – treatment optimization of acute cerebrovascular disorders, which consists of the use of selenase, glutoxim and glutaredoxin as the means of activation of GSH-dependent mechanisms of endogenous neuroprotection. We observed a close direct correlation between the level of reduced glutathione and HSP70 in the cytosolic and mitochondrial fractions of the brain of the test animals. Similar results and data was obtained by us in the process of neurodegeneration experiments in vitro. We observed a close direct correlation between the glutathione recovered and HSP70 when toxic doses of glutamate, CDNB and DNIC were administered. Additionally, a close reverse correlation was observed between the NR-2 peptide and HSP70 in the modeling of glutamate excitotoxicity, and between nitrotyrosin and HSP70 during the deprivation of the systemic level of glutathione and modeling of nitrosative stress. The result of the aforementioned conditions is the presence of severe neurological disorders (53.3% of the test animals), decreased cognitive functions, and a high percentage of deaths in test animals (63.3%) during the acute period of cerebral ischemia. A course of therapy utilizing experimentally substantiated doses of selenase - 50 μg / kg, glutoxim-50 mg / kg and glutaredoxin-200 μl / kg in animals with induced acute cerebrovascular accidents leads to a reduction in mortality by 37.1%, 46.7% and 38.4 %, as well as to a decrease in neurological disturbances of 4,562 points (selenase), 4,033 points (glutoxim), and 4.266 points (glutarethoxine) on the McGraw scale following the 4th day of the experimental treatment. The strength of the neuroprotective effects of selenase, glutoxim and glutaredoxin exceeds (p <0,05) the effects achieved using the referenced control -piracetam.
