The neuroprotective effects of R-phenibut after focal cerebral ischemia

Edijs Vavers, Liga Zvejniece, Baiba Svalbe, Kristine Volska, Elina Makarova, Edgars Liepinsh, Kristina Rizhanova, Vilnis Liepins, Maija Dambrova

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)796-801
Number of pages6
JournalPharmacological Research
Volume113
DOIs
Publication statusPublished - 1 Nov 2016

Keywords

  • BDNF
  • GABA-B receptors
  • R-phenibut
  • Stroke
  • VEGF
  • α-δ subunit of VDCC

Field of Science

  • 3.1 Basic medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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