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(Stroke. 2003;34:1987.)
© 2003 American Heart Association, Inc.

Original Contributions

Astrocytic Gap Junctions Composed of Connexin 43 Reduce Apoptotic Neuronal Damage in Cerebral Ischemia

From the Department of Anatomy and Cell Biology, University of British Columbia, Vancouver, British Columbia, Canada (T.N., C.C.G.N.), and Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.N., S.F.).

Correspondence to Dr Christian C.G. Naus, Department of Anatomy and Cell Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. E-mail cnaus{at}interchange.ubc.ca

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.

Key Words: apoptosis • astrocytes • connexin 43 • gap junctions • stroke

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