Neuroprotective Effects of Resveratrol in Ischemic Brain Injury

Noelia D Machado,David Díaz Díaz,Santiago Grijalvo,Mariana A Fernández,Gorka Villena Armas

doi:10.3390/neurosci2030022

Abstract

Cerebral ischemia represents the third cause of death and the first cause of disability in adults. This process results from decreasing cerebral blood flow levels as a result of the occlusion of a major cerebral artery. This restriction in blood supply generates low levels of oxygen and glucose, which leads to a decrease in the energy metabolism of the cell, producing inflammation, and finally, neurological deterioration. Currently, blood restoration of flow is the only effective approach as a therapy in terms of ischemic stroke. However, a significant number of patients still have a poor 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 by modulating mitochondrial function and have been identified as potential targets for the treatment of cerebral ischemia. In recent years, the beneficial actions of flavonoids and polyphenols against cerebrovascular diseases have been extensively investigated. The use of resveratrol (RSV) has been shown to markedly decrease brain damage caused by ischemia in numerous studies. According to in 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, TLR4 signal transduction regulation, gut/brain axis modulation, GLUT3 up-regulation inhibition, neuronal autophagy activation, and de novo SUR1 expression inhibition. In this review, we summarize the recent outcomes based on the neuroprotective effect of RSV itself and RSV-loaded nanoparticles in vitro and in vivo models focusing on such mechanisms of action as well as describing the potential therapeutic strategies in which RSV plays an active role in cases of ischemic brain injury.

Highlights

Resveratrol (RSV) is a natural stilbene class of polyphenol present in a large variety of vegetal species, such as grapes, mulberries, peanuts, and pomegranates [1]
The results suggested that RSV can ameliorate cerebral ischemic injury in rats since the infarct volume of the RSV-treated group was significantly decreased, the neurological scores were remarkably improved, and the brain water content after reperfusion was reduced in comparison with the non-treated group
This review has collected various recent studies describing the evaluation of the RSV effectiveness in the treatment of ischemic brain injury in different rodent animal models

Summary

Introduction

Resveratrol (RSV) is a natural stilbene class of polyphenol (trans-3,5,4 -trihydroxystilbene) present in a large variety of vegetal species, such as grapes, mulberries, peanuts, and pomegranates [1]. Results showed that treatment with RSV induced activation of AMPK and SIRT1 by inhibiting cyclic nucleotide PDEs. For the development of the studies, in vivo cerebral ischemia injury was induced in 7–8-week-old male Sprague Dawley rats by middle cerebral artery occlusion (MCAO). Results suggested a neuroprotective effect of RSV in MCAO rats since the degree of neurological deficits (based on a 5-point scale) significantly decreased from 2.75 for the control group to 1.67 after RSV treatment (Figure 2). The authors showed that RSV prevented memory deficits in rats and effectively reduced lipid peroxidation involved in programmed cell death cascades and inflammation These preliminary results have served to underscore the potential of RSV in treating ischemia–reperfusion injury in the brain, but further experiments should be properly designed to launch preclinical studies to confirm this capability

Regulation of TLR4 Signal Transduction

Inhibition of GLUT3 Up-Regulation

Findings

Conclusions