title: Brain injury after perinatal hypoxia-ischemia is exacerbated in copper/zinc superoxide dismutase transgenic mice.
abstract: The role of superoxide radical formation in the pathogenesis of perinatal hypoxic-ischemic injury was examined using transgenic (Tg) mice expressing three times normal amounts of copper/zinc-superoxide dismutase (CuZn/SOD). Fourteen litters of postnatal d 7 strain 218/3 mice were subjected to right common carotid artery ligation followed by 90 min of hypoxia in an 8% oxygen/humidified chamber maintained at 37 degrees C. Both Tg mice (n = 32) and their nontransgenic (nTg) littermates (n = 30) survived the injury equally. Evaluation of infarcted brain areas measured by video image analysis of three coronal brain sections through the anterior hippocampus from each animal revealed that the Tg animals suffered brain infarction more frequently than did nTg mice. Blinded histologic scoring of cerebral cortex and striatum 5 d after injury revealed that Tg mice were more likely to have higher histologic severity scores than their nTg littermates (p = 0.0463, Mann-Whitney U test). These findings suggest that brain injury in perinatal hypoxia-ischemia may be mediated in part by free radical formation from excessive hydrogen peroxide or nitric oxide production.
authors.affiliation: Department of Neurology, University of California, San Francisco 94143-0114, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Ditelberg
authors.forename: R A
authors.initials: RA
authors.lastname: Sheldon
authors.forename: C J
authors.initials: CJ
authors.lastname: Epstein
authors.forename: D M
authors.initials: DM
authors.lastname: Ferriero
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000473:pathology*; D002545:Brain Ischemia / Q000401:mortality / Q000473:pathology*; D002544:Cerebral Infarction / Q000473:pathology; D003300:Copper; D004195:Disease Models, Animal; D000860:Hypoxia / Q000401:mortality / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D013534:Survival; D015032:Zinc
chemical_list: D003300:Copper; D013482:Superoxide Dismutase; D015032:Zinc