The Role of Nrf2 in Relieving Cerebral Ischemia-Reperfusion Injury

Abstract

Ischemic stroke includes two related pathological damage processes: brain injury caused by primary ischemia and secondary ischemia reperfusion (I/R) injury. I/R injury has become a worldwide health problem. Unfortunately, there is still a lack of satisfactory drugs for ameliorating cerebral I/R damage. Nrf2 is a vital endogenous antioxidant protein, which combines with Keap1 to maintain a dormant state under physiological conditions. When pathological changes such as I/R occurs, Nrf2 dissociates from Keap1 and activates the expression of downstream antioxidant proteins to exert a protective effect. Recent research have shown that the activated Nrf2 not only effectively inhibits oxidative stress, but also performs the ability to repair the function of compromised mitochondria, alleviate endoplasmic reticulum stress, eliminate inflammatory response, reduce blood-brain barrier permeability, inhibit neuronal apoptosis, enhance the neural network remolding, thereby exerting significant protective effects in alleviating the injuries caused by cell oxygen-glucose deprivation, or animal cerebral I/R. However, no definite clinical application report demonstrated the efficacy of Nrf2 activators in the treatment of cerebral I/R. Therefore, further efforts are needed to elaborate the role of Nrf2 activators in the treatment of cerebral I/R. Here, we reviewed the possible mechanisms underlying its potential pharmacological benefits in alleviating cerebral I/R injury, so as to provide a theoretical basis for studying its mechanism and developing Nrf2 activators.

Keywords: I/R; Nrf2; Stroke; hormesis; ischemic stroke; oxidative stress.