Mice overexpressing extracellular superoxide dismutase have increased resistance to global cerebral ischemia.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Sheng, H; Kudo, M; Mackensen, GB; Pearlstein, RD; Crapo, JD; Warner, DS

Published Date

  • June 2000

Published In

Volume / Issue

  • 163 / 2

Start / End Page

  • 392 - 398

PubMed ID

  • 10833313

Pubmed Central ID

  • 10833313

International Standard Serial Number (ISSN)

  • 0014-4886

Digital Object Identifier (DOI)

  • 10.1006/exnr.2000.7363


  • eng

Conference Location

  • United States