Matrix metalloproteinases increase very early during experimental focal cerebral ischemia

Microvascular integrity is lost during focal cerebral ischemia. The degrada tion of the basal lamina and extracellular matrix are, in part, responsible for the loss of vascular integrity. Matrix metalloproteinases (MMPs) may p lay a pri mary role in basal lamina degradation. By using a sensitive modif ication of gelatin zymography, the authors investigated the activity of MMP -2 and MMP-9 in frozen 10-mu m sections of ischemic and nonischemic basal g anglia and plasma samples of 27 non-human primates after middle cerebral ar tery occlusion/ reperfusion (MCAO/R) for various periods. The gelatinolytic activities were compared with parallel cell dUTP incorporation in the isch emic zones of adjacent sections. In the brain, the integrated density of MM P-2 increased significantly by 1 hour after MCAO and was persistently eleva ted thereafter. Matrix metalloproteinase-2 expression was highly correlated with the extent of neuron injury and the number of injured neurons (r = 0. 9763, SE = 0.004,2P < 0.0008). Matrix metalloproteinase-9 expression only w as significantly increased in subjects with hemorrhagic transformation. In plasma, only MMP-9 increased transiently at 2 hours of MCAO. These findings highlight the early potential role of MMP-2 in the degradation of basal la mina leading to neuronal injury, and an association of MMP-9 with hemorrhag ic transformation after focal cerebral ischemia.