A large amount of clinical and experimental data suggest the involvement of neurotrophins, in particular the brain-derived neurotrophic factor (BDNF), in depression pathogenesis. However, the therapeutic use of BDNF is limited because of its instability in biological fluids, poor blood-brain barrier (BBB) permeability, and the presence of side effects. A low-molecular-weight mimetic GSB-106, which is a substituted dimeric dipeptide bis(N-monosuccinyl-L-seryl-L-lysine)hexamethylenediamide, was designed and synthesized based on the BDNF fourth loop structure at the V.V. Zakusov Institute of Pharmacology (RAMS). GSB-106 was found to exhibit an antidepressant activity in various models of depressive-like state when administered intraperitoneally to outbred mice and rats. An effect for the substance, when administered daily for 4–5 days, was detected in the Porsolt forced swimming test (0.1 and 1.0 mg/kg) and in the tail suspension test in mice (1.0 and 1.5 mg/ kg). An effect for GSB-106 at doses of 0.1 and 0.5 mg/kg was observed after a single application in experiments on rats in the Nomura water wheel test. The obtained evidence supports the hypothesis on the involvement of BDNF in the pathogenesis of various depression conditions, thus opening prospects for searching for new original antidepressants.
The study of novel selective anxiolytic afobazol on rats with experimental intracerebral post-traumatic hematoma (cerebral hemorrhage) demonstrated its efficiency in a dose of 5 mg/kg applied by a single or repeated administration for 2 weeks. The preparation significantly decreased the incidence of neurological disturbances in most rats (pareses, paralyses, convulsive movements, lateral posture). The therapeutic course of afobazol improved survival rate. Afobazol improved learning and memory in rats with cerebral hemorrhage in the conditioned passive avoidance test and positively affected motor activity in the open field test, which was documented by significant increase in total motor activity indices. The effects of afobazol were more pronounced after course treatment. . Address for correspon dence: i_galaeva@mail.ru. I. P. Galaeva Disturbances of cerebral circulation, ischemic strokes and cerebral hemorrhages (CH) belong to leading factors of mortality. The consequences of stroke lead to disablement due to neurological deficiency and disturbances of mnestic and mental functions [3,10]. The most dangerous and resistant to treatment cerebral lesions in CH are caused by blood penetration into adjacent cerebral tissues during intracerebral hemorrhages, hemorrhages into the cerebral ventricles, subarachnoid space, extradural and subdural areas because of pronounced anatomic and physiological shifts, metabolic disturbances (including energy and substrate deficiency) ionic imbalance, glutamate excitotoxicity, oxidative stress, disturbances of enzyme functions, anoxic depolarization of the membranes and the death of neurons [3,8,9].Complex mechanisms of stroke pathogenesis necessitate the development of adequate pharmacotherapeutic methods aimed at restoration of cell homeostasis.To this end, a novel selective anxiolytic afobazol was synthesized at V. V. Zakusov State Research Institute of Pharmacology [6].The mechanism of its action is based on restoration of disturbed functions of GABA A -benzodiazepine receptor complex [6].Afobazol possesses antiradical potency, prevents ischemia-induced intensification of NO production in the brain [7], and exhibits protective properties in simulated glutamate toxicity in vitro. These data corroborate indications on the common links in the mechanisms of anxiogenesis and stroke pathogenesis, and explain importance to study the neuroprotective properties of afobazol.In this paper, we examined the effects of afobazol on survival rate and CNS function in rats with intracerebral post-traumatic hematoma. MATERIALS AND METHODSExperiments were carried out on random-bred albino male rats weighing 200-250 g. The rats were
Human recombinant erythropoietin adsorbed on poly(butyl)cyanoacrylate nanoparticles and administered intraperitoneally in a dose of 0.05 mg/kg exhibited a neuroprotective effect in experimental intracerebral posttraumatic hematomas (hemorrhagic stroke) and reduced animal mortality. Human recombinant erythropoietin, native and adsorbed on lactic and glycolic acid copolymer-based nanoparticles, exhibited no antistroke effect on this model. Analysis of reverse transcription PCR products showed that human recombinant erythropoietin adsorbed on poly(butyl)cyanoacrylate nanoparticles more than 2-fold increased the expression of BDNF and NGF neurotrophins in the rat brain frontal cortex and hippocampus.
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