title: Inflammatory mechanisms involved in brain injury following cardiac arrest and cardiopulmonary resuscitation.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacy, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China; Department of Emergency, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Yanxiao
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Department of Orthopedics, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Chest Pain Center, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China; Institute of Emergency and Critical Care Medicine, Shandong University, Jinan, Shandong 250012, P.R. China; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Wang
authors.affiliation: Chest Pain Center, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China; Institute of Emergency and Critical Care Medicine, Shandong University, Jinan, Shandong 250012, P.R. China; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Luetao
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacy, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Anchang
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Emergency, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China; Chest Pain Center, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China; Institute of Emergency and Critical Care Medicine, Shandong University, Jinan, Shandong 250012, P.R. China; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Yuguo
authors.initials: Y
authors.lastname: Chen
keywords: astrocyte; cardiac arrest; cardiopulmonary resuscitation; inflammatory response; microglia; neurological impairment