OBJECTIVE:Identification of the role of oxidative stress in the development of disorders that occur in hemorrhagic stroke (HS, post-traumatic intracerebral hematoma), and the study of the effects of Mexidol on neurological and cognitive deficits in HS with an analysis of the relationship between the therapeutic effects of the drug in HS with its antioxidant effect.MATERIAL AND METHODS:The study was carried out on mature outbred male rats weighing 260-280 g. HS was created by destruction of the brain tissue in the area of the capsula interna, with the introduction of blood into the site of injury. On the 1st, 7th, and 14th days after HS modeling, death, neurological deficits (McGrow scale, rotating rod), convulsive manifestations, and cognitive impairment were recorded in rats; blood plasma and homogenates of the cerebral cortex of rats. Mexidol was administered after the HS operation: first at a dose of 150 mg/kg, intraperitoneally, for 3 days and then 75 mg/kg, orally (from the 4th to the 14th day).RESULTS:Mexidol in rats with HS significantly increases the survival rate of animals, reduces the manifestations of neurological deficits according to the McGrow scale (playpen movements, paresis of 1-4 limbs, paralysis of the lower limbs, lateral position), eliminates individual motor convulsive manifestations, restores impaired coordination of movements (rotating rod test) and improves, impaired HS, learning and memory processes. Mexidol normalizes the concentration of TBA-active products in the blood of animals and homogenates of the cerebral cortex of rats, both a day and 7 days after HS modeling.CONCLUSION:The data obtained indicate the involvement of oxidative stress as a chain of pathogenesis in the development of disorders in HS and the ability of Mexidol to alleviate neurological deficits, convulsive manifestations and cognitive impairment in HS, which is accompanied by a decrease in oxidative stress. All this justifies the importance of the use of Mexidol in patients with hemorrhagic stroke, posttraumatic intracerebral hematoma and determines the features of its therapeutic effects.

The “learned helplessness” (LH) model in rats is widely used in a battery of tests to assess depression-like behaviour and the effects of antidepressants. The model is considered to be suffi ciently valid, though having some limitations with reproducibility. This review discusses the possibilities of using the model for assessing the symptoms of a depressive-like state and the pathogenesis of depression, as well as the effects of antidepressants. The factors affecting the reproducibility of the LH model are described, the most important of which is the different sensitivity of animals to stress. Several protocols for the induction and testing of LH, which are used by different research teams, are presented. Due to the diffi culty of comparing the results obtained using different LH protocols, LH models should be standardized for use in individual laboratories. LH models are worth using in preclinical studies of potential drugs exhibiting antidepressant activity.

The effects of GSB-106, a low-molecular mimetic of BDNF loop 4, that represents a substituted dimeric dipeptide bis (N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide, on cognitive and motor impairments in a model of a depressive-like state in rats caused by unavoidable electric foot-shock were studied using active avoidance and open-field tests. GSB-106 (0.5 mg/kg, per os , 10 days) completely restored the number of avoidance reactions that was reduced in rats exposed to foot-shock and the percentage of trained rats in active avoidance training. In the open-field test, the peptide restored reduced horizontal activity and the number of explored holes. Thus, GSB-106 corrected impaired learning and memory, as well as locomotor activity and exploratory behavior in a model of depression in rats.

The review provides and describes in detail the main most commonly used behavioral experimental models of depression. Endophenotypes and criteria of validity of behavioral methods for evaluation of antidepressant activity in compounds are described. Modeling depression using laboratory animals allows us to understand the nature of depression in humans and to search for effective ways of treating.

The review provides and describes in detail the main most commonly used behavioral experimental models of depression. Endophenotypes and criteria of validity of behavioral methods for evaluation of antidepressant activity in compounds are described. Modeling depression using laboratory animals allows us to understand the nature of depression in humans and to search for effective ways of treating.

Dimeric dipeptide mimethic human nerve growth factor, bis-(N-monosucciniL-gLycyL-Lysine), GK-2h at doses 0,1, 0,5, 1,0, 1,5 mg/kg, i.p. has an antiamnesic effect on the modeLs of scopoLamine, maximaL eLectroshock or ketamin induced passive avoidance response amnesia. GK-2h at doses 1,0-1,5 mg/ kg possess weak antihypoxic und anticonvuLsive properties, it does not affect the expLoratory behavior of animaLs in the test of open fieLd.

The protective effects of a new low-molecular-weight mimetic of nerve growth factor hexamethylene diamide bis-(N-monosuccinyl-L-glutamine-L-lysine; GK-2) were studied on the experimental model of hemorrhagic stroke (intracerebral posttraumatic hematoma) in rats. Intraperitoneal injections of GK-2 in a dose of 1 mg/kg 4 and 24 h after surgery and 24 h before testing the CNS function on days 3, 7, and 14 prevent death of experimental animals, reduce the neurological deficit, and normalized behavior.

Effects of the novel antiparkinsonian drug himantane and amantadin were studied in rats with intracerebral posttraumatic hematoma. Drugs were administered first at 3.5 hours after surgery and then for 4 consecutive days. Effects were registered on days 1, 3, 7 and 14 after surgery. It was shown that both drugs significantly decreased mortality and improved motor activity, exploratory behavior and memory. Amantadin was more effective in tests for motor activity and exploratory behavior. Himantane 5 mg/kg i.p demonstrated the more pronounced activity in restoring memory. The results obtained testify for neuroprotective properties of the novel antiparkinsonian drug himantane.

Intraperitoneal administration of afobazole in a dose of 0.1 mg/kg over 2 weeks after repeated modeling of intracerebral post-traumatic hematoma reduces animal mortality, decreases motor coordination disturbances, and improves learning and memory processes in rats.

The model of posttraumatic hematoma was used to imitate the condition of hemorrhagic stroke in rats. Afobazole (5-ethoxy-2-[2-(morpholino)-ethylthio] benzimidazole dihydrochloride) administered in doses of 0.1 and 1.0 mg/kg intraperitoneally for 14 days was shown to be able to decrease the pathological manifestations of this model. Afobazole administration decreased mortality and the neurological deficits, including motor discoordination, and improve the learning and memory.

Changes in proline-specific peptidase activity in the frontal cortex and hippocampus were studied using the experimental model of retrograde amnesia in rats. In one group, the amnesia was produced by a single injection of M-cholinergic antagonist scopolamine and the other group received the maximal electroconvulsive stimulation (MES). The amnesic effect was evaluated in passive avoidance test. In the amnesia models under consideration, the activity of prolylendopeptidase was significantly increased in both frontal cortex and hippocampus. The activity of dipeptidyl peptidase IV was significantly decreased in the cortex, whereas in the hippocampus it remained unchanged. Pyracetam inhibited prolylendopeptidase in the cortex and hippocampus, whereas dipeptidyl peptidase IV activity remained unchanged.

Исследованы изменения активности пролинспецифических пептидаз во фронтальной коре и гиппокампе при экспериментальной ретроградной амнезии. У одной группы крыс амнезию вызывали однократным введением м-холиноблокатора скополамина, у другой - максимальным электрошоковым воздействием. Амнезирующий эффект оценивали в методике условного рефлекса пассивного избегания. При использованных моделях амнезии активность пролилэндопептидазы достоверно возрастает как в коре, так и в гиппокампе. Активность дипептидилпептидазы IV снижается в коре и остается неизмененной в гиппокампе. Пирацетам снижает активность пролилэндопептидазы во фронтальной коре и гиппокампе и не влияет на активность дипептидилпептидазы IV.

The effect of piracetam and novel substituted prolylcontaining dipeptide noopept (Nphenyl-acetylLprolyl-glycine ethyl easter, GVS111) was studied in rats with hemorrhagic stroke (HS) intracerebral posttraumatic hematoma localizated in the capsule interna. Single and 14days long administration of noopept (0,5 mg/kg, i.p.) or piracetam (200 mg/kg i.p.) as a reference drug was used with the first administration in 4 hours after the lesion. Noopept was shown to diminish the degree of the neurological disturbances caused by HS and to improve the retrieval in passive avoidance task. Piracetam was found to decrease the degree of the neurological deficit caused by experimental HS. Noopept exceeds piracetam in terms of effectiveness. The results obtained are testifying to the pronounced protective effect of noopept in the model of intracerebral posttraumatic hematoma in rats. The mechanisms of noopept activity aredisscused.