Cardiac arrest (CA) is a leading cause of death and long-term disability worldwide.Recent advances in cardiopulmonary resuscitation (CPR) have improved survival rates,however,the survivors are prone tosevere neurologic injury after successful CPR following CA.Effective therapeutic options to protect the brain from CA remain limited,due to the complexities of the injury cascades causedby global cerebral ischemia/reperfusion (I/R).Although the precise mechanisms of neurological impairment following CA-initiated I/R injury need to be clarified,evidence supports that one of the key cellular pathway of cerebral injury is inflammation.The inflammatory response is orchestrated by activated glial cells in response to I/R injury.Increased release of danger-associated pattern molecules (DAPMs) and cellular dysfunction in activated microglia and astrocytes contribute to ischemia-induced cytotoxic and pro-inflammatory cytokines generation,and ultimately to delayed death of neurons.Furthermore,cytokines and adhesion molecules generated within activated microglia as well as astrocytes take part in innate immune response;modulate influx of peripheral immune and inflammatory cells into the brain,resulting in neurological injury.This review will discuss the molecular aspects of immune and inflammatory mechanisms in global cerebral I/R injury following CA and CPR and potential therapeutic strategies that target neuroinflammation and the innate immune system.