Preventive Effects of Resveratrol on Endocannabinoid System and Synaptic Protein Modifications in Rat Cerebral Cortex Challenged by Bilateral Common Carotid Artery Occlusion and Reperfusion

Int J Mol Sci. 2018 Jan 31;19(2):426. doi: 10.3390/ijms19020426.


This study aims to evaluate the putative roles of a single acute dose of resveratrol (RVT) in preventing cerebral oxidative stress induced by bilateral common carotid artery occlusion, followed by reperfusion (BCCAO/R) and to investigate RVT's ability to preserve the neuronal structural integrity. Frontal and temporal-occipital cortices were examined in two groups of adult Wistar rats, sham-operated and submitted to BCCAO/R. In both groups, 6 h before surgery, half the rats were gavage-fed with a single dose of RVT (40 mg/per rat in 300 µL of sunflower oil as the vehicle), while the second half received the vehicle alone. In the frontal cortex, RVT pre-treatment prevented the BCCAO/R-induced increase of lipoperoxides, augmented concentrations of palmitoylethanolamide and docosahexaenoic acid, increased relative levels of the cannabinoid receptors type 1 (CB1) and 2 (CB2), and peroxisome-proliferator-activated-receptor (PPAR)-α proteins. Increased expression of CB1/CB2 receptors mirrored that of synaptophysin and post-synaptic density-95 protein. No BCCAO/R-induced changes occurred in the temporal-occipital cortex. Collectively, our results demonstrate that, in the frontal cortex, RVT pre-treatment prevents the BCCAO/R-induced oxidative stress and modulates the endocannabinoid and PPAR-α systems. The increased expression of synaptic structural proteins further suggests the possible efficacy of RVT as a dietary supplement to preserve the nervous tissue metabolism and control the physiological response to the hypoperfusion/reperfusion challenge.

Keywords: PPAR-α; bilateral common carotid artery occlusion; cerebral cortex; endocannabinoid system; lipoperoxides; resveratrol; synaptic proteins.

MeSH terms

  • Animals
  • Arterial Occlusive Diseases
  • Carotid Artery Diseases*
  • Frontal Lobe / drug effects*
  • Frontal Lobe / metabolism
  • Gene Expression Regulation
  • Male
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar
  • Receptors, Cannabinoid / drug effects*
  • Receptors, Cannabinoid / genetics
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Resveratrol
  • Stilbenes / pharmacology*
  • Stilbenes / therapeutic use


  • Receptors, Cannabinoid
  • Stilbenes
  • Resveratrol