Cardiac arrest (CA) is a leading cause of fatality and long-term disability worldwide. Recent advances in
cardiopulmonary resuscitation (
CPR) have improved survival rates; however, the survivors are prone to severe neurological
injury subsequent to successful
CPR following CA. Effective therapeutic options to protect the brain from CA remain limited, due to the complexities of the injury cascades caused by global
cerebral ischemia/reperfusion (I/R). Although the precise mechanisms of neurological impairment following CA-initiated I/R injury require further clarification, evidence supports that one of the key cellular pathways 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 molecular pattern molecules 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, are involved in the innate immune response; modulate influx of peripheral immune and inflammatory cells into the brain, resulting in neurological injury. The present review discusses the molecular aspects of immune and inflammatory mechanisms in global cerebral I/R injury following CA and
CPR, and the potential therapeutic strategies that target
neuroinflammation and the innate immune system.