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

Abstract

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.

• Authors: E V Volotova, I S Filina, D A Bakulin, D V Kurkin, I N Tyurenkov
• Journal: Eksperimental'naia i klinicheskaia farmakologiia (Eksp Klin Farmakol) Vol. 79 Issue 4 Pg. 18-25 (Aug 2016) ISSN: 0869-2092 [Print] Russia (Federation)
• PMID: 29949699 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Immunosuppressive Agents
• Lipopolysaccharides
• Myelin Basic Protein
• Neuroprotective Agents
• Glutamic Acid
• gamma-Aminobutyric Acid
• Cyclosporine
• Phosphopyruvate Hydratase
• 4-amino-3-phenylbutyric acid

Topics

• Animals
• Animals, Outbred Strains
• Biomarkers (blood)
• Brain Ischemia (drug therapy, immunology, mortality, physiopathology)
• Carotid Artery, Common (surgery)
• Cerebrovascular Circulation (drug effects)
• Cyclosporine (pharmacology)
• Glutamic Acid (pharmacology)
• Immunity, Innate
• Immunosuppression Therapy (methods)
• Immunosuppressive Agents (pharmacology)
• Ligation
• Lipopolysaccharides (administration & dosage)
• Locomotion (drug effects)
• Male
• Muscle Strength (drug effects)
• Myelin Basic Protein (blood, genetics)
• Neuroprotective Agents (pharmacology)
• Orientation, Spatial (drug effects)
• Phosphopyruvate Hydratase (blood, genetics)
• Rats
• Survival Analysis
• gamma-Aminobutyric Acid (analogs & derivatives, pharmacology)