2001/12/01 by Yvan Gasche, Jean-Christophe Copin, Taku Sugawara +2
Biochemistry, Genetics and Molecular Biology · Medicine · #Acute Ischemic Stroke Management #Intracerebral and Subarachnoid Hemorrhage Research #Protease and Inhibitor Mechanisms
paper · pdf · doi:10.1097/00004647-200112000-00003
openalex publication_date 2001/12/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Oxidative stress generated during stroke is a critical event leading to blood-brain barrier (BBB) disruption with secondary vasogenic edema and hemorrhagic transformation of infarcted brain tissue, restricting the benefit of thrombolytic reperfusion. In this study, the authors demonstrate that ischemia-reperfusion-induced BBB disruption in mice deficient in copper/zinc-superoxide dismutase (SOD1) was reduced by 88% ( P < 0.0001) and 73% ( P < 0.01), respectively, after 3 and 7 hours of reperfusion occurring after 1 hour of ischemia by the inhibition of matrix metalloproteinases. Accordingly, the authors show that local metalloproteinase-generated proteolytic imbalance is more intense in ischemic regions of SOD1 mice than in wild-type litter mates. Moreover, active in situ proteolysis is, for the first time, demonstrated in ischemic leaking capillaries that produce reactive oxygen species. By showing that oxidative stress mediates BBB disruption through metalloproteinase activation in experimental ischemic stroke, this study provides a new target for future therapeutic strategies to prevent BBB disruption and potentially reperfusion-triggered intracerebral hemorrhage.