Overexpression of copper and zinc superoxide dismutase in transgenic mice prevents the induction and activation of matrix metalloproteinases after cold injury-induced brain trauma

Matrix metalloproteinases (MMPs), a family of proteolytic enzymes which deg rade the extracellular matrix, are implicated in blood-brain barrier disrup tion, which is a critical event leading to vasogenic edema. To investigate the role of reactive oxygen species (ROS) in the expression of MMPs in vaso genic edema, the authors measured gelatinase activities before and after co ld injury (CI) using transgenic mice that overexpress superoxide dismutase- 1. A marked induction of pro-gelatinase B (pro-MMP-9) was seen 2 hours afte r CI and was maximized at 12 hours in wild-type mice. The pro-MMP-9 level w as significantly lower in transgenic mice 4 hours (P < 0.001) and 12 hours (P < 0.05) after CI compared to wild-type mice. The activated MMP-9 was det ected from 6 to 24 hours after injury. A mild induction of pro-gelatinase a (pro-MMP-2) was seen at 6 hours and was sustained until 7 days. In contras t, the activated form of MMP-2 appeared at 24 hours, was maximized at 7 day s, and was absent in transgenic mice. Western blot analysis showed that the tissue inhibitors of metalloproteinases were not modified after CI. The re sults suggest that ROS production after CI may contribute to the induction and/or activation of MMPs and could thereby exacerbate endothelial cell inj ury and the development of vasogenic edema after injury.