Neuroprotective Effects of Resveratrol in Ischemic Brain Injury

Abstract

Cerebral ischemia represents the third cause of death and the first cause of disability inadults. This process results from decreasing cerebral blood flow levels as a result of the occlusionof a major cerebral artery. This restriction in blood supply generates low levels of oxygen andglucose, which leads to a decrease in the energy metabolism of the cell, producing inflammation, andfinally, neurological deterioration. Currently, blood restoration of flow is the only effective approachas a therapy in terms of ischemic stroke. However, a significant number of patients still have apoor prognosis, probably owing to the increase in the generation of reactive oxygen species (ROS)during the reperfusion of damaged tissue. Oxidative stress and inflammation can be avoided bymodulating mitochondrial function and have been identified as potential targets for the treatmentof cerebral ischemia. In recent years, the beneficial actions of flavonoids and polyphenols againstcerebrovascular diseases have been extensively investigated. The use of resveratrol (RSV) has beenshown to markedly decrease brain damage caused by ischemia in numerous studies. According toin vitro and in vivo experiments, there is growing evidence that RSV is involved in several pathways,including cAMP/AMPK/SIRT1 regulation, JAK/ERK/STAT signaling pathway modulation, TLR4signal transduction regulation, gut/brain axis modulation, GLUT3 up-regulation inhibition, neuronalautophagy activation, and de novo SUR1 expression inhibition. In this review, we summarize therecent outcomes based on the neuroprotective effect of RSV itself and RSV-loaded nanoparticlesin vitro and in vivo models focusing on such mechanisms of action as well as describing the potentialtherapeutic strategies in which RSV plays an active role in cases of ischemic brain injury