Abstract Number: Esoc2026a278 Inhibition of the Nlrp3 Inflammasome Reduces Neuroinflammation and Improves Functional Outcomes in Acute Ischemic Stroke: A Translational Experimental Study

Abstract Background and aims Activation of the NLRP3 inflammasome is a key driver of post-ischemic neuroinflammation, contributing to neuronal death and blood–brain barrier disruption. Targeting this pathway may offer an effective neuroprotective strategy in acute ischemic stroke. To evaluate whether pharmacological inhibition of the NLRP3 inflammasome attenuates neuroinflammation and improves functional recovery after experimental ischemic stroke. Methods A transient middle cerebral artery occlusion (tMCAO) model was induced in adult male rats (n=48). Animals were randomized to receive either the selective NLRP3 inhibitor MCC950 (10 mg/kg, intraperitoneal) or vehicle control at reperfusion and again at 24 hours. Primary outcomes included infarct volume (TTC staining) and neurological deficit scores at 24 and 72 hours. Secondary outcomes assessed NLRP3/Caspase-1 activation, IL-1β production (Western blot and ELISA), and integrity of the blood–brain barrier (Evans Blue assay). Statistical analysis was performed using ANOVA with post-hoc testing. Results MCC950 treatment significantly reduced infarct volume by 32% compared with controls (p0.01) and improved neurological deficit scores at both 24 and 72 hours (p0.05). Molecular analysis demonstrated a marked reduction in NLRP3 expression (−41%), Caspase-1 activation (−36%), and IL-1β levels (−48%) in the treatment group (all p0.01). Blood–brain barrier permeability was significantly preserved (p0.05). No adverse systemic effects were observed. Conclusions Pharmacological inhibition of the NLRP3 inflammasome provides substantial neuroprotection in experimental ischemic stroke, reducing inflammation and improving early neurological outcomes. These findings support further investigation of NLRP3-targeted therapies as potential adjunctive treatments in acute stroke management. Conflict of interest NA