In line, knocking down the expression of caveolin-1 in rat brain microvascular endothelial cells results in increased MMP activity; since nitric oxide mediates the upregulation of caveolin-1 in rat brain microvessels following focal cerebral ischemia-reperfusion injury, inhibition of nitric oxide production reduces BBB permeability by indirectly inhibiting MMP activity [138]. Here, CAV1 is linked to brain ischemia.