The cytosolic antioxidant, copper/zinc superoxide dismutase, attenuates blood-brain barrier disruption and oxidative cellular injury after photothrombotic cortical ischemia in mice

Oxidative stress has been associated with the development of blood-brain ba rrier disruption and cellular injury after ischemia. The cytosolic antioxid ant, copper/zinc superoxide dismutase, has been shown to protect against bl ood-brain barrier disruption and infarction after cerebral ischemia-reperfu sion. However, it is not clear whether copper/zinc superoxide dismutase can protect against evolving ischemic lesions after thromboembolic cortical is chemia. In this study, the photothrombotic ischemia model, which is physiol ogically similar to thromboembolic stroke, was used to develop cortical isc hemia. Blood-brain barrier disruption and oxidative cellular damage were in vestigated in transgenic mice that overexpress copper/zinc superoxide dismu tase and in littermate wild-type mice after photothrombotic ischemia, which was induced by both injection of erythrosin B (30 mg/kg) and irradiation u sing a helium neon laser for 3 min. Free radical production, particularly s uperoxide, was increased in the lesioned cortex as early as 4 h after ische mia using hydroethidine in situ detection. The transgenic mice showed a pro minent decrease in oxidative stress compared with the wild-type mice. Blood -brain barrier disruption, evidenced by quantitation of Evans Blue leakage, occurred I h after ischemia and gradually increased up to 24 h. Compared w ith the wild-type mice, the transgenic mice showed less blood-brain barrier disruption, a decrease in oxidative DNA damage using 8-hydroxyguanosine im munohistochemistry, a subsequent decrease in DNA fragmentation using the in situ nick-end labeling technique, and decreased infarct volume after ische mia. From these results we suggest that superoxide anion radical is an important factor in blood-brain barrier disruption and oxidative cellular injury, an d that copper/zinc superoxide dismutase could protect against the evolving infarction after thromboembolic cortical ischemia. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.