Inflammatory responses involved in post-cardiac arrest brain injury: mechanisms, regulation, and therapeutic potential

Abstract

Neuroinflammation plays a key role in the pathogenesis of post-cardiac arrest (CA) brain injury. Innate immune cells sense a variety of danger signals through pattern-recognition receptors and evoke rapidly after ischemic challenge, triggering inflammatory responses and amplifying brain damage. A programmed cell death (PCD) pathway is activated after ischemic and/or inflammatory stimuli, leading to the elimination of the damaged cells. However, PCD also regulates inflammatory responses flexibly. The present review aimed to summarize the mechanisms of inflammatory responses, including the biology of immune cells, the innate immune recognition that initiates the inflammation, and the immunomodulatory effects of PCD following CA. Promising therapeutic approaches of targeting inflammatory responses to alleviate brain injury and improve neurological outcomes after CA are also reviewed.