The neuroprotective effects of R-phenibut after focal cerebral ischemia.

Abstract

R-phenibut is a γ-aminobutyric acid (GABA)-B receptor and α2-δ subunit of the voltage-dependent calcium channel (VDCC) ligand. The aim of the present study was to test the effects of R-phenibut on the motor, sensory and tactile functions and histological outcomes in rats following transient middle cerebral artery occlusion (MCAO). In this study, MCAO was induced by filament insertion (f-MCAO) or endothelin-1 (ET1) microinjection (ET1-MCAO) in male Wistar or CD rats, respectively. R-phenibut was administrated at doses of 10 and 50mg/kg for 14 days in the f-MCAO or 7 days in the ET1-MCAO. The vibrissae-evoked forelimb-placing and limb-placing tests were used to assess sensorimotor, tactile and proprioceptive function. Quantitative reverse transcriptase-PCR was used to detect brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) gene expression in the damaged brain hemisphere. Both f-MCAO and ET1-MCAO resulted in statistically significant impairment of sensorimotor function and brain infarction. R-phenibut at a dose of 10mg/kg significantly improved histological outcome at day 7 in the ET1-MCAO. R-phenibut treatment at a dose of 50mg/kg significantly alleviated reduction of brain volume in damaged hemisphere in both f-MCAO and ET1-MCAO. In R-phenibut treated animals a trend of recovery of tactile and proprioceptive stimulation in the vibrissae-evoked forelimb-placing test was observed. After R-phenibut treatment at a dose of 50mg/kg statistically significant increase of BDNF and VEGF gene expression was found in damaged brain hemisphere. Taken together, obtained results provide evidence for the neuroprotective activity of R-phenibut in experimental models of stroke. These effects might be related to the modulatory effects of the drug on the GABA-B receptor and α2-δ subunit of VDCC.

• Authors: Edijs Vavers, Liga Zvejniece, Baiba Svalbe, Kristine Volska, Elina Makarova, Edgars Liepinsh, Kristina Rizhanova, Vilnis Liepins, Maija Dambrova
• Journal: Pharmacological research (Pharmacol Res) Vol. 113 Issue Pt B Pg. 796-801 (11 2016) ISSN: 1096-1186 [Electronic] Netherlands
• PMID: 26621244 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Brain-Derived Neurotrophic Factor
• Calcium Channels
• Eye Proteins
• Neuroprotective Agents
• R-photopsin
• Receptors, GABA-B
• Vascular Endothelial Growth Factor A

Topics

• Animals
• Brain Ischemia (drug therapy, metabolism)
• Brain-Derived Neurotrophic Factor (metabolism)
• Calcium Channels (metabolism)
• Disease Models, Animal
• Eye Proteins (pharmacology)
• Forelimb (drug effects, metabolism)
• Infarction, Middle Cerebral Artery (drug therapy, metabolism)
• Male
• Neuroprotective Agents (pharmacology)
• Rats
• Rats, Wistar
• Receptors, GABA-B (metabolism)
• Sensorimotor Cortex (drug effects, metabolism)
• Stroke (drug therapy, metabolism)
• Vascular Endothelial Growth Factor A (metabolism)