Astrocytic gap junctions composed of connexin 43 reduce apoptotic neuronal damage in cerebral ischemia

Taizen Nakase, Shinji Fushiki, Christian C.G. Naus

Research output: Contribution to journalArticlepeer-review

176 Citations (Scopus)

Abstract

Background and Purpose - Astrocytes may play a vital role in neuroprotection by providing energy substrates to neurons and regulating the concentration of K+ and neurotransmitters through gap junctions. Connexin 43 (Cx43) is one of the major gap junction proteins in astrocytes. We have shown that, after focal stroke, heterozygote Cx43 null (Cx43+/-) mice exhibited larger infarction volumes than wild-type (Cx43+/+) mice. We explored the underlying mechanism by which gap junctional intercellular communication influences astrocytic activation and neuroprotection in ischemia. Methods - Both Cx43+/- and Cx43+/+ mice underwent right side permanent middle cerebral artery occlusion (MCAO). Mice were prepared by transcardial perfusion, and at 24 hours and 4 days after surgery, brains were prepared for immunohistochemistry or Western blot analysis. Results - Four days after MCAO, Cx43+/- mice showed severe apoptosis in the penumbral lesion compared with Cx43+/+ mice. The level of caspase-3 was significantly higher in the stroke lesion of Cx43+/- mice than in Cx43+/+ mice. Four days after MCAO, Cx43+/- mice showed a significantly larger infarct volume but a smaller area of astrogliosis than did Cx43+/+ mice. The penumbra of Cx43+/- mice showed an increased level of Cx30 compared with Cx43+/+ mice. Conclusions - Gap junctions may play an important role in astrocytic activation. Reactive astrocytes may reduce neuronal apoptosis under ischemia by regulating extracellular conditions through their gap junction.

Original languageEnglish
Pages (from-to)1987-1993
Number of pages7
JournalStroke
Volume34
Issue number8
DOIs
Publication statusPublished - 2003 Aug 1
Externally publishedYes

Keywords

  • Apoptosis
  • Astrocytes
  • Connexin 43
  • Gap junctions
  • Stroke

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

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