Connexin43 null mutation increases infarct size after stroke.
Glial-neuronal interactions have been implicated in both normal information processing and neuroprotection. One pathway of cellular interactions involves gap junctional intercellular communication (GJIC). In astrocytes, gap junctions are composed primarily of the channel protein connexin43 (Cx43) and provide a substrate for formation of a functional syncytium implicated in the spatial buffering capacity of astrocytes. To study the function of gap junctions in the brain, we used heterozygous Cx43 null mice, which exhibit reduced Cx43 expression. Western blot analysis showed a reduction in the level of Cx43 protein and GJIC in astrocytes cultured from heterozygote mice. The level of Cx43 is reduced in the adult heterozygote cerebrum to 40% of that present in the wild-type. To assess the effect of reduced Cx43 and GJIC on neuroprotection, we examined brain infarct volume in wild-type and heterozygote mice after focal ischemia. In our model of focal stroke, the middle cerebral artery was occluded at two points, above and below the rhinal fissure. Four days after surgery, mice were killed, the brains were sectioned and analyzed. Cx43 heterozygous null mice exhibited a significantly larger infarct volume compared with wild-type (14.4 +/- 1.4 mm(3) vs. 7.7 +/- 0.82 mm(3), P < 0.002). These results suggest that augmentation of GJIC in astrocytes may contribute to neuroprotection after ischemic injury.
Siushansian
R
R
Department of Anatomy and Cell Biology, The University of Western Ontario, London, ON, Canada N6A 5C1.
Bechberger
J F
JF
Cechetto
D F
DF
Hachinski
V C
VC
Naus
C C
CC
D000818:Animals; D001253:Astrocytes / Q000166:cytology; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics*; D005260:Female; D017629:Gap Junctions / Q000473:pathology / Q000502:physiology; D006579:Heterozygote; D006720:Homozygote; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020521:Stroke / Q000473:pathology*
D018031:Connexin 43