Glia and hemichannels: key mediators of perinatal encephalopathy

作     者：Robert Galinsky Joanne O.Davidson Justin M.Dean Colin R.Green Laura Bennet Alistair J.Gunn 

作者机构：Department of Physiology University of Auckland The Ritchie Centre Hudson Institute of Medical Research Department of Ophthalmology University of Auckland 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2018年第13卷第2期

页      面：181-189页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100211[医学-妇产科学] 10[医学] 

基　　金：supported by the Health Research Council of New Zealand(grant 17/601) the Auckland Medical Research Foundation National Health and Medical Research Council CJ Martin Early Career Fellowship(grant No.1090890 to RG) the Victorian Government Operational Infrastructure Support Program 

主　　题：hypoxia-ischemia connexin hemichannels spreading injury connexin 43 astrocytes hypoxicischemic encephalopathy 

摘      要：Perinatal encephalopathy remains a major cause of disability, such as cerebral palsy. Therapeutic hypo- thermia is now well established to partially reduce risk of disability in late preterm/term infants. However, new and complementary therapeutic targets are needed to further improve outcomes. There is increasing evidence that glia play a key role in neural damage after hypoxia-ischemia and infection/inflammation. In this review, we discuss the role of astrocytic gap junction （connexin） hemichannels in the spread of neural injury after hypoxia-ischemia and/or infection/inflammation. Potential mechanisms of hemichannel medi- ated injury likely involve impaired intraceUular calcium handling, loss of blood-brain barrier integrity and release of adenosine triphosphate （ATP） resulting in over-activation of purinergic receptors. We propose the hypothesis that inflammation-induced opening of connexin hemichannels is a key regulating event that initiates a vicious cycle of excessive ATP release, which in turn propagates activation of purinergic receptors on microglia and astrocytes. This suggests that developing new neuroprotective strategies for preterm infants will benefit from a detailed understanding of glial and connexin hemichannel responses.