Glial-neuronal interactions have been implicated in both normal information
processing and neuroprotection. One pathway of cellular interactions invol
ves gap junctional intercellular communication (GJIC. In astrocytes, gap ju
nctions 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 l
evel 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 GJ
IC on neuroprotection, we examined brain infarct volume in wild-type and he
terozygote mice after focal ischemia. In our model of focal stroke, the mid
dle cerebral artery was occluded at two points, above and below the rhinal
fissure. Four days after surgery, mice were killed, the brains were section
ed and analyzed. Cx43 heterozygous null mice exhibited a significantly larg
er infarct volume compared with wild-type (14.4 +/- 1.4 mm(3) 7.7 +/- 0.82
mm(3), P < 0.002). These results suggest that augmentation of GJIC in astro
cytes may contribute to neuroprotection after ischemic injury. (C) 2001 Wil
ey-Liss, Inc.