CASP1 and cardiac arrest: We demonstrate that (1) cardiac arrest leads to microglial activation and leukocytes infiltration in the brain; (2) cardiac arrest triggers microglial pyroptosis and increases the caspase-1 activity in the activated microglia population, which is mediated by the NLRP3 inflammasome; and (3) targeting NLRP3 and caspase-1 with MCC950 and Ac-YVAD-cmk significantly prevent microglial pyroptosis and consequential inflammatory response after cardiac arrest, which further leads to improved neurologic outcome and less histological injury in cardiac arrest-modeling rats.