Neuroprotective role of astrocytic gap junctions in ischemic stroke.
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.
Nakase
Taizen
T
Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Fushiki
Shinji
S
Söhl
Goran
G
Theis
Martin
M
Willecke
Klaus
K
Naus
Christian C G
CC
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
D018845:CD11 Antigens; D018031:Connexin 43