Research progress of NLRP3 inflammasome in cerebral ischemia and related diseases

<?A3B2 tlsb=-.03w?>The NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome is a multiprotein complex that recognises endogenous and exogenous danger signals such as bacterial toxins and mitochondrial reactive oxygen species, playing a central role in innate immunity and the regulation of inflammatory responses. In recent years, NLRP3 <?A3B2 pi129?>has emerged as a key molecule in the field of cerebral ischaemia, with its activation closely associated with the post-stroke cerebral inflammatory microenvironment. In the context of cerebral ischemia, NLRP3 <?A3B2 pi129?>plays a critical role in neuropathology. Following ischemic stroke, NLRP3 <?A3B2 pi129?>is activated by multiple upstream signals, including the TLR4/NF-κB pathway, reactive oxygen species (ROS), mitochondrial damage, release of mitochondrial DNA (mtDNA), and calcium overload. Through these activation pathways, NLRP3 <?A3B2 pi129?>mediates key pathological processes such as proinflammatory cytokine release (e.g., IL-1β and IL-18), pyroptosis (inflammatory cell death), and oxidative stress. These events directly increase cerebral infarct volume, disrupt the integrity of the bloodbrain barrier (BBB), and exacerbate neurological deficits, leading to poor functional outcomes. Moreover, NLRP3 <?A3B2 pi129?>serves as a pivotal hub in the crosstalk between the central nervous system and peripheral inflammatory responses. It can indirectly influence the prognosis of cerebral ischemia by modulating peripheral pathological processes. Specifically, NLRP3 <?A3B2 pi129?>contributes to the development and progression of major cerebral ischemia risk factors, including atherosclerosis, glucose metabolism disorders (e.g., diabetes), and gut-brain axis dysregulation (such as gut microbiota dysbiosis). Conversely, targeted inhibition of the NLRP3 <?A3B2 pi129?>inflammasome not only blocks the central inflammatory cascade but also ameliorates these peripheral risk factors, thereby reducing the risk and severity of cerebral ischemia fundamentally. Therefore, therapeutic strategies aimed at inhibiting the NLRP3 <?A3B2 pi129?>inflammasome—whether by blocking its activation pathways, enhancing mitochondrial autophagy, regulating noncoding RNAs, or by administering small molecule inhibitors or natural medicines—can simultaneously address both central nervous system inflammation and peripheral comorbidities. Such dual target approaches strategies are highly promising for substantially reducing ischemic brain injury and enhancing poststroke recovery. <alternatives id="alt1"> </alternatives>