Mice overexpressing extracellular superoxide dismutase have increased resistance to global cerebral ischemia.
Transgenic mice, which exhibit a fivefold increase in brain parenchymal extracellular superoxide dismutase (EC-SOD) activity, were used to investigate the role of EC-SOD in global ischemic brain injury. Halothane-anesthetized normothermic wild-type (n = 22) and transgenic (n = 20) mice underwent 10 min of near-complete forebrain ischemia induced by bilateral carotid artery occlusion and systemic hypotension (mean arterial pressure = 30 mm Hg). After 3 days of recovery, the brains were histologically examined. Other mice underwent autoradiographic determination of regional CBF 10 min prior to, during, and 30 min after forebrain ischemia. Histologic injury in the cortex and caudoputamen was minimal in both groups. The percentage of dead hippocampal CA1 neurons was reduced in the EC-SOD transgenic group (wild type = 44 +/- 28%; EC-SOD transgenic = 23 +/- 21%, mean +/- SD, P = 0.015). CBF was similar between groups prior to ischemia. The intraischemic blood flow was severely reduced in forebrain structures and was similar between groups. Blood flow at 30 min postischemia had recovered to 50-60% of baseline values in both groups. These results indicate that EC-SOD can play an important role in defining the magnitude of selective neuronal necrosis resulting from near-complete forebrain ischemia. This implicates involvement of extracellular superoxide anions in the pathologic response to global cerebral ischemia.
Sheng
H
H
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Kudo
M
M
Mackensen
G B
GB
Pearlstein
R D
RD
Crapo
J D
JD
Warner
D S
DS
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016548:Prosencephalon / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism*
D013482:Superoxide Dismutase