中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (2): 181-189.doi: 10.4103/1673-5374.226378

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

胶质和半通道:围产期脑病的关键调解人

  

  • 收稿日期:2018-01-25 出版日期:2018-02-15 发布日期:2018-02-15

Glia and hemichannels: key mediators of perinatal encephalopathy

Robert Galinsky1, 2, Joanne O. Davidson1, Justin M. Dean1, Colin R. Green3, Laura Bennet1, Alistair J. Gunn1   

  1. 1 Department of Physiology, University of Auckland, Auckland, New Zealand
    2 The Ritchie Centre, Hudson Institute of Medical Research, Victoria, Australia
    3 Department of Ophthalmology, University of Auckland, Auckland, New Zealand
  • Received:2018-01-25 Online:2018-02-15 Published:2018-02-15
  • Contact: Alistair Jan Gunn, MBChB,Ph.D.,aj.gunn@auckland.ac.nz.
  • Supported by:

     The study was 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) and the Victorian Government Operational Infrastructure Support Program.

摘要:

orcid:0000-0003-0656-7035(Alistair Jan Gunn)

Abstract:

Perinatal encephalopathy remains a major cause of disability, such as cerebral palsy. Therapeutic hypothermia 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 mediated 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.

Key words: hypoxia-ischemia, connexin hemichannels, spreading injury, connexin 43, astrocytes, hypoxicischemic encephalopathy