title: Astrocytic gap junctions composed of connexin 43 reduce apoptotic neuronal damage in cerebral ischemia.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Anatomy and Cell Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Taizen
authors.initials: T
authors.lastname: Nakase
authors.forename: Shinji
authors.initials: S
authors.lastname: Fushiki
authors.forename: Christian C G
authors.initials: CC
authors.lastname: Naus
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D018031:Connexin 43 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D017629:Gap Junctions / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006579:Heterozygote; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009474:Neurons / Q000378:metabolism* / Q000473:pathology
chemical_list: D018031:Connexin 43; D005904:Glial Fibrillary Acidic Protein; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases