Extracellular superoxide dismutase overexpression improves behavioral outcome from closed head injury in the mouse

Oxidative stress is known to play an important role in the response of brai n to traumatic insults. We tested the hypothesis that increased extracellul ar superoxide dismutase (EC-SOD) expression can reduce injury in a mouse mo del of closed head injury. Neurologic, cognitive, and histologic outcomes w ere compared between transgenic mice exhibiting a fivefold increase in EC-S OD activity and wild-type littermate controls. Severe or moderate transcran ial impact was induced in anesthetized and physiologically controlled anima ls. After severe impact, transgenic mice had better neurological outcome at 24 hr postinjury (p = 0.038), Brain water content was increased, but there was no difference between groups. Moderate impact resulted in predominantl y mild neurologic deficits in both groups at both 24 hr and 14 days postinj ury, Morris water maze performance, testing cognitive function at 14-17 day s after trauma, was better in EC-SOD overexpressors (p = 0.018), No differe nces were observed between groups for histologic damage in hippocampal CA1 and CA3, We conclude that EC-SOD has a beneficial effect on behavioral outc ome after both severe and moderate closed head injury in mice. Because EC-S OD is believed to be predominantly located in the extracellular space, thes e data implicate an adverse effect of extracellular superoxide anion on out come from closed head injury.