The neuroprotective effects of R-phenibut after focal cerebral ischemia

详细信息    查看全文

• 作者：Edijs Vavers^a ; ^b ; ^{edijs@biomed.lu.lv" class="auth_mail" title="E-mail the corresponding author} ; Liga Zvejniece^a ; Baiba Svalbe^a ; Kristine Volska^a ; ^b ; Elina Makarova^a ; Edgars Liepinsh^a ; Kristina Rizhanova^c ; Vilnis Liepins^c ; Maija Dambrova^a ; ^b
• 关键词：R-phenibut ; GABA-B receptors ; Stroke ; BDNF ; VEGF ; α2-δ subunit of VDCC
• 刊名：Pharmacological Research
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：113
• 期：part_PB
• 页码：796-801
• 全文大小：1056 K

文摘

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 50 mg/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 10 mg/kg significantly improved histological outcome at day 7 in the ET1-MCAO. R-phenibut treatment at a dose of 50 mg/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 50 mg/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.