The Connexin43 C-Terminal Region Mediates Neuroprotection During Stroke

Connexin43 plays an important role in neuroprotection in experimental stroke models; reducing the expression of this gap junction protein in astrocytes enhances injury upon middle cerebral artery occlusion (MCAO). Because the C-terminal region of connexin43 isimportant for channel activity, we carri...

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Bibliographic Details
Published in:	Journal of neuropathology and experimental neurology Vol. 69; no. 2; pp. 196 - 206
Main Authors:	Kozoriz, Michael G, Bechberger, John F, Bechberger, Geralyn R, Suen, Michael W.H, Moreno, Alonso P, Maass, Karen, Willecke, Klaus, Naus, Christian C
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD American Association of Neuropathologists, Inc 01-02-2010 Lippincott Williams & Wilkins Oxford University Press
Subjects:	Animals Astrocytes - pathology Biological and medical sciences Blotting, Western Brain - pathology Brain Ischemia - metabolism Brain Ischemia - pathology Calcium - metabolism Cell Death Cells, Cultured Connexin 43 - chemistry Connexin 43 - metabolism Electric Conductivity Gap Junctions Gliosis - pathology Immunohistochemistry Ion Channel Gating Medical sciences Mice Mice, Inbred C57BL Mice, Transgenic Neurology Neuroprotective Agents - metabolism Protein Structure, Tertiary Stroke - metabolism Stroke - pathology Stroke - physiopathology Structure-Activity Relationship Stroke Nervous system diseases Neuroglia Cell junction Cardiovascular disease Astrocyte Gap junction Cerebral disorder Microglia Vascular disease Connexin Gliosis Ischemia Central nervous system disease Coupling Cerebrovascular disease
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Summary:	Connexin43 plays an important role in neuroprotection in experimental stroke models; reducing the expression of this gap junction protein in astrocytes enhances injury upon middle cerebral artery occlusion (MCAO). Because the C-terminal region of connexin43 isimportant for channel activity, we carried out MCAO stroke experiments in mice expressing a truncated form of connexin43 (Cx43ΔCT mice). Brain sections were analyzed for infarct volume, astrogliosis, and inflammatory cell invasion 4 days after MCAO. Adult cortices and astrocyte cultures were examined for connexin43 (Cx43) expression by immunohistochemistry and Western blot. Cultured astrocytes were also examined for dye coupling, channel conductance, hemichannel activity, and Ca wave propagation. The Cx43ΔCT mice exhibit enhanced cerebral injury after stroke. Astrogliosis was reduced and inflammatory cell invasion was increased inthe peri-infarct region in these mice compared with controls; Cx43 expression was also altered. Lastly, cultured astrocytes from Cx43ΔCT mice were less coupled and displayed alterations in channel gating, hemichannel activity, and Ca wave properties. These results suggest that astrocytic Cx43 contributed to the regulation of cell death after stroke and support the view that the Cx43 C-terminal region is important in protection in cerebral ischemia.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-3069 1554-6578
DOI:	10.1097/NEN.0b013e3181cd44df