title: Neuroprotective role of astrocytic gap junctions in ischemic stroke.
abstract: The role of astrocytic gap junctions in ischemia remains controversial. Several studies support that astrocytic gap junctions play a role in the spread of hypoxic injury, while other reports have demonstrated that blocking astrocytic gap junctions increases neuronal death. Using a stroke model on animals in which the astrocytic gap junction protein connexin43 (Cx43) was compromised, we explored the neuroprotective role of astrocytic gap junctions. A focal brain stroke was performed on heterozygous Cx43 null [Cx43(+/-)] mice, wild type [Cx43(+/+)] mice, astrocyte-directed Cx43 deficient [Cx43(fl/ fl)/hGFAP-cre] mice (here designated as Cre(+) mice), and their corresponding controls [Cx43(fl/fl)] (here designated as Cre(-) mice). Four days following stroke, ischemic lesions were measured for size and analyzed immunohistochemically. Stroke volume was significantly larger in Cx43(+/-) and Cre(+) mice compared to Cx43(+/+) and Cre(-) mice, respectively. Apoptosis as detected by TUNEL labeling and caspase-3 immunostaining was amplified in Cx43(+/-) and Cre(+) mice compared to their control groups. Furthermore, increased inflammation as characterized by the immunohistochemical staining of the microglial marker CD11b was observed in the Cre(+) mice penumbra. Astrocytic gap junctions may reduce apoptosis and inflammation in the penumbra following ischemic insult, suggesting that coupled astrocytes fulfill a neuroprotective role under ischemic stroke conditions.
authors.affiliation: Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Taizen
authors.initials: T
authors.lastname: Nakase
authors.forename: Shinji
authors.initials: S
authors.lastname: Fushiki
authors.forename: Goran
authors.initials: G
authors.lastname: Söhl
authors.forename: Martin
authors.initials: M
authors.lastname: Theis
authors.forename: Klaus
authors.initials: K
authors.lastname: Willecke
authors.forename: Christian C G
authors.initials: CC
authors.lastname: Naus
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D018845:CD11 Antigens / Q000276:immunology; D002450:Cell Communication / Q000502:physiology*; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D020521:Stroke / Q000378:metabolism* / Q000473:pathology
chemical_list: D018845:CD11 Antigens; D018031:Connexin 43