Glia and hemichannels:key mediators of perinatal encephalopathy
Robert Galinsky
Joanne O. Davidson
Justin M. Dean
Colin R. Green
Laura Bennet
Alistair J. Gunn
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 intracellular 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.
机标关键词：
资助基金：The study was supported by the Health Research Council of New Zealand(grant 17/601)the Auckland Medical Research Foun-dation,National Health and Medical Research Council CJ Martin Early Career Fellowship(grant 1090890 to RG)
论文发表日期：2018-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：9( 181-189 )
英文信息