PMID- 26621244 OWN - NLM STAT- MEDLINE DCOM- 20171215 LR - 20180625 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 113 IP - Pt B DP - 2016 Nov TI - The neuroprotective effects of R-phenibut after focal cerebral ischemia. PG - 796-801 LID - S1043-6618(15)30122-5 [pii] LID - 10.1016/j.phrs.2015.11.013 [doi] AB - R-phenibut is a gamma-aminobutyric acid (GABA)-B receptor and alpha(2)-delta 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 alpha(2)-delta subunit of VDCC. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Vavers, Edijs AU - Vavers E AD - Latvian Institute of Organic Synthesis, Riga, Latvia; Riga Stradins University, Riga, Latvia. Electronic address: edijs@biomed.lu.lv. FAU - Zvejniece, Liga AU - Zvejniece L AD - Latvian Institute of Organic Synthesis, Riga, Latvia. FAU - Svalbe, Baiba AU - Svalbe B AD - Latvian Institute of Organic Synthesis, Riga, Latvia. FAU - Volska, Kristine AU - Volska K AD - Latvian Institute of Organic Synthesis, Riga, Latvia; Riga Stradins University, Riga, Latvia. FAU - Makarova, Elina AU - Makarova E AD - Latvian Institute of Organic Synthesis, Riga, Latvia. FAU - Liepinsh, Edgars AU - Liepinsh E AD - Latvian Institute of Organic Synthesis, Riga, Latvia. FAU - Rizhanova, Kristina AU - Rizhanova K AD - JSC Olainfarm, Olaine, Latvia. FAU - Liepins, Vilnis AU - Liepins V AD - JSC Olainfarm, Olaine, Latvia. FAU - Dambrova, Maija AU - Dambrova M AD - Latvian Institute of Organic Synthesis, Riga, Latvia; Riga Stradins University, Riga, Latvia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151124 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Calcium Channels) RN - 0 (Eye Proteins) RN - 0 (Neuroprotective Agents) RN - 0 (R-photopsin) RN - 0 (Receptors, GABA-B) RN - 0 (Vascular Endothelial Growth Factor A) SB - IM MH - Animals MH - Brain Ischemia/*drug therapy/metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - Calcium Channels/metabolism MH - Disease Models, Animal MH - Eye Proteins/*pharmacology MH - Forelimb/drug effects/metabolism MH - Infarction, Middle Cerebral Artery/drug therapy/metabolism MH - Male MH - Neuroprotective Agents/*pharmacology MH - Rats MH - Rats, Wistar MH - Receptors, GABA-B/metabolism MH - Sensorimotor Cortex/*drug effects/metabolism MH - Stroke/drug therapy/metabolism MH - Vascular Endothelial Growth Factor A/metabolism OTO - NOTNLM OT - BDNF OT - GABA-B receptors OT - R-phenibut OT - Stroke OT - VEGF OT - alpha(2)-delta subunit of VDCC EDAT- 2015/12/02 06:00 MHDA- 2017/12/16 06:00 CRDT- 2015/12/02 06:00 PHST- 2015/10/21 00:00 [received] PHST- 2015/11/19 00:00 [revised] PHST- 2015/11/20 00:00 [accepted] PHST- 2015/12/02 06:00 [pubmed] PHST- 2017/12/16 06:00 [medline] PHST- 2015/12/02 06:00 [entrez] AID - S1043-6618(15)30122-5 [pii] AID - 10.1016/j.phrs.2015.11.013 [doi] PST - ppublish SO - Pharmacol Res. 2016 Nov;113(Pt B):796-801. doi: 10.1016/j.phrs.2015.11.013. Epub 2015 Nov 24.