Protective Effect of Resveratrol on the Brain in a Rat Model of Epilepsy

Neurosci Bull. 2017 Jun;33(3):273-280. doi: 10.1007/s12264-017-0097-2. Epub 2017 Feb 4.

Abstract

Accumulating evidence has suggested resveratrol as a promising drug candidate for the treatment of epilepsy. To validate this, we tested the protective effect of resveratrol on a kainic acid (KA)-induced epilepsy model in rats and investigated the underlying mechanism. We found that acute resveratrol application partially inhibited evoked epileptiform discharges in the hippocampal CA1 region. During acute, silent and chronic phases of epilepsy, the expression of hippocampal kainate glutamate receptor (GluK2) and the GABAA receptor alpha1 subunit (GABAAR-alpha1) was up-regulated and down-regulated, respectively. Resveratrol reversed these effects and induced an antiepileptic effect. Furthermore, in the chronic phase, resveratrol treatment inhibited the KA-induced increased glutamate/GABA ratio in the hippocampus. The antiepileptic effects of resveratrol may be partially attributed to the reduction of glutamate-induced excitotoxicity and the enhancement in GABAergic inhibition.

Keywords: Epilepsy; GABA; Glutamate; Hippocampus; Resveratrol.

MeSH terms

  • Animals
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / pharmacology*
  • CA1 Region, Hippocampal* / drug effects
  • CA1 Region, Hippocampal* / metabolism
  • CA1 Region, Hippocampal* / physiopathology
  • Disease Models, Animal
  • Down-Regulation
  • Epilepsy, Temporal Lobe* / chemically induced
  • Epilepsy, Temporal Lobe* / drug therapy
  • Epilepsy, Temporal Lobe* / metabolism
  • Excitatory Amino Acid Agonists / pharmacology
  • GluK2 Kainate Receptor
  • Glutamic Acid / drug effects*
  • Kainic Acid / pharmacology
  • Male
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / drug effects
  • Receptors, Kainic Acid / drug effects
  • Resveratrol
  • Stilbenes / administration & dosage
  • Stilbenes / pharmacology*
  • Up-Regulation
  • gamma-Aminobutyric Acid / drug effects*

Substances

  • Anticonvulsants
  • Excitatory Amino Acid Agonists
  • Gabra1 protein, rat
  • Neuroprotective Agents
  • Receptors, GABA-A
  • Receptors, Kainic Acid
  • Stilbenes
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Resveratrol
  • Kainic Acid