Mitochondrial mechanisms in Cerebral Ischemia-Reperfusion Injury: Unravelling the intricacies

Abstract

Cerebral ischemic stroke is a major contributor to physical impairments and premature death worldwide. The available reperfusion therapies for stroke in the form of mechanical thrombectomy and intravenous thrombolysis increase the risk of cerebral ischemia–reperfusion (I-R) injury due to sudden restoration of blood supply to the ischemic region. The injury is manifested by hemorrhagic transformation, worsening of neurological impairments, cerebral edema, and progression to infarction in surviving patients. A complex network of multiple pathological processes has been known to be involved in the pathogenesis of I-R injury. Primarily, 3 major contributors namely oxidative stress, neuroinflammation, and mitochondrial failure have been well studied in I-R injury. A transcription factor, Nrf2 (Nuclear factor erythroid 2-related factor 2) plays a crucial defensive role in resisting the deleterious effects of I-R injury and potentiating the cellular protective mechanisms. In this review, we delve into the critical function of mitochondria and Nrf2 in the context of cerebral I-R injury. We summarized how oxidative stress, neuroinflammation, and mitochondrial anomaly contribute to the pathophysiology of I-R injury and further elaborated the role of Nrf2 as a pivotal guardian of cellular integrity. The review further highlighted Nrf2 as a putative therapeutic target for mitochondrial dysfunction in cerebral I-R injury management.