TY - JOUR
T1 - Protection against hypoxic-ischemic injury in transgenic mice overexpressing Kir6.2 channel pore in forebrain
AU - Héron-Milhavet, Lisa
AU - Xue-Jun, Yang
AU - Vannucci, Susan J.
AU - Wood, Teresa L.
AU - Willing, Lisa B.
AU - Stannard, Bethel
AU - Hernandez-Sanchez, Catalina
AU - Mobbs, Charles
AU - Virsolvy, Anne
AU - LeRoith, Derek
PY - 2004/4
Y1 - 2004/4
N2 - The role of the K-ATP channel pore-forming subunit Kir6.2 on protection from cerebral hypoxic-ischemic injury was assessed in transgenic mice overexpressing normal Kir6.2 or a dominant negative form (AFA) of this subunit in the forebrain. The resulting mice overexpress either the Kir6.2 or the AFA transgene mainly in the cerebral cortex and hippocampus. The Kir6.2 transgenic mice are resistant to hypoxic-ischemic injury showing a decreased region of cortical damage as compared to the dominant negative AFA and the wild-type mice. Moreover, the overexpression of Kir6.2 allowed an important silencing of the neurons present in forebrain regions thus protecting them from ischemic injury. Interestingly, the phenotype observed in Kir6.2 transgenic mice was observed without increased sulfonylurea binding. Taken together, these results indicate that the transgenic overexpression of Kir6.2 in forebrain significantly protects mice from hypoxic-ischemic injury and neuronal damage seen in stroke.
AB - The role of the K-ATP channel pore-forming subunit Kir6.2 on protection from cerebral hypoxic-ischemic injury was assessed in transgenic mice overexpressing normal Kir6.2 or a dominant negative form (AFA) of this subunit in the forebrain. The resulting mice overexpress either the Kir6.2 or the AFA transgene mainly in the cerebral cortex and hippocampus. The Kir6.2 transgenic mice are resistant to hypoxic-ischemic injury showing a decreased region of cortical damage as compared to the dominant negative AFA and the wild-type mice. Moreover, the overexpression of Kir6.2 allowed an important silencing of the neurons present in forebrain regions thus protecting them from ischemic injury. Interestingly, the phenotype observed in Kir6.2 transgenic mice was observed without increased sulfonylurea binding. Taken together, these results indicate that the transgenic overexpression of Kir6.2 in forebrain significantly protects mice from hypoxic-ischemic injury and neuronal damage seen in stroke.
UR - http://www.scopus.com/inward/record.url?scp=11144354704&partnerID=8YFLogxK
U2 - 10.1016/j.mcn.2003.10.012
DO - 10.1016/j.mcn.2003.10.012
M3 - Article
C2 - 15080888
AN - SCOPUS:11144354704
SN - 1044-7431
VL - 25
SP - 585
EP - 593
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 4
ER -