Mitochondrial targeting strategies for mitigating oxidative damage and enhancing neuroprotection in ischemic stroke: A Review.

Ischemic stroke (IS) is one of the leading causes of permanent disability and mortality worldwide. It is characterized by the interruption of cerebral blood flow, causing acute oxygen and glucose deprivation, triggering pathological processes such as mitochondrial dysfunction, oxidative stress, inflammation, and cell death. Ischemic stroke constitutes the majority of all incident strokes, and regardless of its underlying cause, mitochondrial dysfunction is a universal feature of its pathophysiological cascade. Mitochondria play a key role in energy regulation, apoptosis, and the inflammatory response through the NLRP3 inflammasome. Modulation of their fusion, fission, and turnover dynamics is an emerging therapeutic strategy aimed at preserving their functional integrity. In this context, mitochondrial transplantation has shown promising results in animal models and initial clinical trials, representing a potential revolution in the management of IS. Research into therapies targeting mitochondria not only broadens the pathophysiological understanding of stroke but also offers new therapeutic opportunities with significant clinical impact.