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.
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.
Authors: Panagiotis Bargiotas; Antje Krenz; Sheriar G Hormuzdi; Dirk A Ridder; Anne Herb; Waleed Barakat; Silvia Penuela; Jakob von Engelhardt; Hannah Monyer; Markus Schwaninger Journal: Proc Natl Acad Sci U S A Date: 2011-12-06 Impact factor: 11.205
Authors: Jorge E Contreras; Helmuth A Sánchez; Loreto P Véliz; Feliksas F Bukauskas; Michael V L Bennett; Juan C Sáez Journal: Brain Res Brain Res Rev Date: 2004-12