ncRNAs-Mediated Pyroptosis in Cerebral Ischemia-Reperfusion Injury: Pathophysiology, Mechanisms, and Therapeutic Perspectives.

Cerebral ischemia-reperfusion injury (CIRI) is a complex pathological process triggered by transient obstruction of blood flow and subsequent reperfusion, ultimately leading to intracellular disturbances such as oxidative stress, inflammatory responses, and programmed cell death. Among the various types of cell death, pyroptosis (an inflammatory kind of regulated cell death) has received increasing attention due to its involvement in key neurovascular unit cells, including endothelial cells, neurons, microglia, and astrocytes. Intriguingly, accumulating evidence demonstrates that non-coding RNAs (ncRNAs), including long non-coding RNAs, microRNAs, and circular RNAs, can modulate multiple stages of pyroptosis in CIRI. This review synthesizes recent findings on the ncRNAs-regulated pyroptosis in CIRI. We highlight the molecular underpinnings of pyroptotic activation following ischemic injury and discuss how ncRNAs shape these mechanisms. By elucidating the interactions between ncRNAs and pyroptosis-related pathways, we intend to present innovative viewpoints for early diagnosis and the development of potential therapeutic strategies to mitigate CIRI.