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.

Ischemia–reperfusion injury (IRI) is a prevalent pathological process in clinical settings characterized by complex pathogenesis involving the interplay of oxidative stress, inflammation, mitochondrial dysfunction, and diverse cell death pathways. Fundamentally, IRI manifests as a complication arising from reperfusion therapies aimed at restoring blood flow following ischemia. Despite the existence of various therapeutic strategies, the development of effective interventions for IRI remains a significant challenge. Rutin, a low-molecular-weight flavonoid glycoside ubiquitously present in vegetables, fruits, and herbal medicines, exhibits promising therapeutic potential due to its pleiotropic biological activities, including antioxidant, anti-inflammatory, and cytoprotective effects against cell death. This review systematically elucidates the molecular mechanisms underlying the protective effects of rutin against IRI and synthesizes evidence from preclinical studies regarding its diverse modes of action. However, the clinical application of rutin is currently hampered by its relatively low bioavailability. Future research should prioritize the development of innovative pharmaceutical formulations to enhance its bioavailability, thereby fully unlocking its clinical translational value.