Edema formation exacerbates neurological and histological outcomes after focal cerebral ischemia in CuZn-superoxide dismutase gene knockout mutant mice.
In a variety of studies. CuZn-superoxide dismutase (CuZn-SOD) has been shown to protect against ischemic brain injury. A possible role for CuZn-SOD-related modulation of neuronal viability has been suggested by the finding that CuZn-SOD inhibits brain edema formation following various kinds of neurological insults. We have evaluated the role of CuZn-SOD on brain edema formation following focal cerebral ischemia in mice bearing a disruption of the CuZn-SOD gene (Sod1). Homozygous mutants (Sod1-/-) had no detectable CuZn-SOD activity and heterozygous mutants (Sod1+/-) showed a 50% decrease compared to wild-type mice. Sod1-/- mice showed a high level of blood-brain barrier (BBB) disruption shortly after 1 hr of middle cerebral artery occlusion and 100% mortality at 24 hr following ischemia. Sod1+/- mice showed a moderate level of BBB disruption and 30% mortality. The Sod1+/- animals had increased infarct volume and brain swelling, accompanying exacerbated neurological deficits at 24 hr following ischemia. These results indicate the important role of superoxide anions in the development of brain edema after focal cerebral ischemia and suggest the possibility that brain edema formation may contribute to the exacerbation of ischemic brain injury and neurological deficits in knockout mutant mice.
Kondo
T
T
Department of Neurological Surgery, University of California, School of Medicine, San Francisco, USA.
Reaume
A G
AG
Huang
T T
TT
Murakami
K
K
Carlson
E
E
Chen
S
S
Scott
R W
RW
Epstein
C J
CJ
Chan
P H
PH
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000473:pathology; D001812:Blood-Brain Barrier / Q000502:physiology; D001929:Brain Edema / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D006579:Heterozygote; D006720:Homozygote; D002546:Ischemic Attack, Transient / Q000235:genetics / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D013482:Superoxide Dismutase / Q000235:genetics*; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; D013482:Superoxide Dismutase