NEUROPROTECTIVE ACTION OF PHENIBUT AND NEUROGLUTAM IN EXPERIMENTAL CEREBRAL ISCHEMIA ON THE BACKGROUND OF ALTERED IMMUNOREACTIVITY.

Cerebroprotective activity of phenyl derivatives of GABA (phenibut, 25 mg/kg) and L-glutamic acid (neuroglutam, 26 mg/kg) in rats with cerebral ischemia was studied on the background of intact and altered immunoreactivity. Tested compounds were administered intraperitoneally for 7 days after two phase ligation of common carotid arteries (second artery was ligated 3 days after ligation of the first artery). Immunosuppression caused by cyclosporin (daily dose 5 mg/kg, p.o., for 13 days) worsened brain ischemia outcome, as manifested by increased mortality, more severe neurological marker score, increased levels of brain damage markers (NSE and MBP) in the blood serum, decrease in muscle strength and locomotor activity, and impairment of orientation and research activity as compared to animals with brain ischemia and intact immunity. Activation of immune system was caused by lipopolysaccharide (10 mg/kg, i.p., 7 injections every second day). Upon activation of the immune system, brain ischemia produced lower mortality, while the survived rats exhibited more favorable outcome of ischemia than animals with suppression of immune system: lover neurological marker score, lower blood serum NSE and MBP levels (-35% on average,p < 0.05), and much higher level of performance in motor coordination, muscular strength, and locomotor activity (+90% on average, p < 0.05). The state of immune system significantly influenced the neuroprotective activity of drugs tested. Neuroglutam administration produced positive effect both in animals with intact immunity and on the background of altered immunoreactivity. However, most positive outcome after neuroglutam administration in ischemic rats was observed in animals with suppression of immune system, with significant increase in the cerebral blood flow level (+56%), decrease in NSE and MBP blood serum levels (57 and 76%, respectively) after 7-day treatment as compared to the control group. The therapeutic potential of phenibut was somewhat lower than that of neuroglutam, and it was more pronounced in rats with activated immune system, whereas the drug effectiveness in rats with suppressed immune system was less pronounced.

[The influence of the immunity activation and suppression on the outcome of brain ischemia]. / Ishemiia golovnogo mozga na fone podavleniia i aktivatsii immuniteta.

AIM: To explore the influence of the immunity activation and suppression on the outcome of brain ischemia in experimental animals. MATERIAL AND METHODS: Brain ischemia has been modulated by irreversible staged bilateral common carotid arteries occlusion. Suppression of the immune system has been conducted by administration of cyclosporin A (5 mg/kg, per os). Activation of the immune system has been conducted by administration of lipopolysaccharide (10 mkg/kg, i.p.). RESULTS: Authors have established that in animals with immunosuppression there is an increase in the concentration of the neuron specific proteins in blood serum (NSE and MBP), mortality (by 20%) and severity of neurological deficit (by 33%). Rats with immunosuppression have reduced general locomotor activity (by 44%), exploratory behavior in the Open Field Test (by 43%) and decrease in the motor activity in the Rotarod Test (by 19%) compared to the group of rats with brain ischemia and intact immune systems. During the immunity activation after brain ischemia injury, the decrease in NSE and MBP levels, mortality (by 15%) and severity of neurological deficit (by 13%) as well as higher concentrations of neurotrophins BDNF and NGF and higher general locomotor activity of animals (by 34%) and physical endurance (by 55%) in the Open Field and Rotarod Tests, respectively, were observed. CONCLUSION: Immunosupression negatively affected the outcome of brain ischemia.