Mitochondrial Regulatory Network: Multi-dimensional Pathological Mechanism of Ischemic Stroke and New Strategies for...

Ischemic stroke is characterized by limited therapeutic options and a high rate of longterm disability. The majority of strokes are ischemic in nature and result from cerebral vascular occlusion, leading to substantial neurological damage and patient burden. The complexity of poststroke neurological recovery poses a major challenge to modern medicine. Following ischemic stroke, a cascade of pathophysiological processes is initiated in the brain, among which mitochondrial dysfunction plays a central role. Abnormal mitochondrial function directly contributes to neuronal death and subsequent loss of neurological function. Therefore, elucidating mitochondriarelated pathological mechanisms in ischemic stroke is critical for the development of effective therapeutic strategies. In this review, we summarize current evidence on the regulation of mitochondrial function by the mitochondrial genome following ischemic stroke. We further examine the involvement of mitochondria in key cellular processes, including programmed cell death, autophagy, and ferroptosis, within the ischemic brain. In addition, we discuss the role of physical exercise in restoring mitochondrial function after stroke as an important adjunct to pharmacological therapies. Finally, we highlight emerging mitochondria-targeted therapeutic strategies for ischemic stroke, with particular emphasis on nanotechnology and stem cell-based interventions. This review aims to provide a comprehensive understanding of the multifaceted roles of mitochondria in ischemic stroke and to offer insights for future research and therapeutic development.