The pathogenesis of cerebral ischemia also involves the breakdown of matrix-cell adhesions, which results in the disruption of the BBB and ultimately neuronal death and brain damage. PPARδ may regulate these responses by decreasing activity of matrix metalloproteinases (MMPs), enzymes that degrade structural proteins in the extracellular matrix and that have been implicated in ischemia-induced parenchymal and vascular damage. In particular, treatment of VSMCs with the PPARδ agonist, GW501516, reduced MMP-9 enzymatic activity 24 h after oxygen-glucose deprivation (OGD). Furthermore, VSMC-selective PPARδ knockout mice exhibited increased MMP-9 expression following MCAO, and inhibition of MMP-9 using shRNA reduced infarct size and vascular permeability in these mice [13]. More studies, however, are needed to understand the mechanism by which PPARδ regulates MMP-9 expression.
