Inflammatory pathways in cerebral ischemia- reperfusion injury: Focus on the NLRP3 inflammasome

Abstract

Cerebral ischemia-reperfusion injury (CIRI) is a severe neurological disorder characterized by exacerbated brain tissue damage and deteriorated neurological function following the restoration of blood flow after ischemia. The NLRP3 inflammasome, a multi-protein assembly triggered by diverse danger-associated signals, is critically involved in the inflammatory processes underlying CIRI. Its triggering prompts the secretion of IL-1β and IL-18, which in turn amplifies inflammatory reactions, promote neuronal apoptosis and necrosis, disrupt the blood-brain barrier, and impair neurological recovery. This review systematically examines the NLRP3 inflammasome’s structural architecture, activation mechanisms, and regulatory pathways, and discusses its close association with CIRI. Additionally, current intervention strategies targeting the NLRP3 inflammasome, including pharmacological inhibitors and traditional Chinese medicine, are summarized, along with future research directions for developing novel treatments and personalized therapies. Elucidating the detailed molecular mechanisms of the NLRP3 inflammasome in CIRI is critical for enhancing therapeutic efficacy and patient prognosis.