Targeting NLRP3 and caspase-1 with two highly selective inhibitors MCC950 and Ac-YVAD-cmk dramatically reduced the number of microglia undergoing pyroptosis, the number of infiltrating leukocytes, the elevated level of IL-1β and IL-18, improved neurologic outcome, and alleviated neuronal injury in cardiac arrest-modeling rats. Here, NLRP3 is linked to cardiac arrest.