title: 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.affiliation: Latvian Institute of Organic Synthesis, Riga, Latvia; Riga Stradins University, Riga, Latvia. Electronic address: edijs@biomed.lu.lv.
authors.forename: Edijs
authors.initials: E
authors.lastname: Vavers
authors.affiliation: Latvian Institute of Organic Synthesis, Riga, Latvia.
authors.forename: Liga
authors.initials: L
authors.lastname: Zvejniece
authors.affiliation: Latvian Institute of Organic Synthesis, Riga, Latvia.
authors.forename: Baiba
authors.initials: B
authors.lastname: Svalbe
authors.affiliation: Latvian Institute of Organic Synthesis, Riga, Latvia; Riga Stradins University, Riga, Latvia.
authors.forename: Kristine
authors.initials: K
authors.lastname: Volska
authors.affiliation: Latvian Institute of Organic Synthesis, Riga, Latvia.
authors.forename: Elina
authors.initials: E
authors.lastname: Makarova
authors.affiliation: Latvian Institute of Organic Synthesis, Riga, Latvia.
authors.forename: Edgars
authors.initials: E
authors.lastname: Liepinsh
authors.affiliation: JSC Olainfarm, Olaine, Latvia.
authors.forename: Kristina
authors.initials: K
authors.lastname: Rizhanova
authors.affiliation: JSC Olainfarm, Olaine, Latvia.
authors.forename: Vilnis
authors.initials: V
authors.lastname: Liepins
authors.affiliation: Latvian Institute of Organic Synthesis, Riga, Latvia; Riga Stradins University, Riga, Latvia.
authors.forename: Maija
authors.initials: M
authors.lastname: Dambrova
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000494:pharmacology*; D005552:Forelimb / Q000187:drug effects / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism; D066191:Sensorimotor Cortex / Q000187:drug effects* / Q000378:metabolism; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015220:Calcium Channels; D005136:Eye Proteins; D018696:Neuroprotective Agents; C058835:R-photopsin; D018080:Receptors, GABA-B; D042461:Vascular Endothelial Growth Factor A
keywords: BDNF; GABA-B receptors; R-phenibut; Stroke; VEGF; α(2)-δ subunit of VDCC