Pivotal Role For Beta-1 Integrin In Neurovascular Remodelling After Ischemic Stroke

β1 integrin is a cell surface molecule that is critical for endothelial cell adhesion, migration and survival during angiogenesis. In the present study we employed in vivo and in vitro models to elucidate the role of β1 integrin in vascular remodelling and stroke outcomes. At 24 h after cerebral ischemia and reperfusion (I/R), the ischemic cortex (ipsilateral area) exhibited modest β1 integrin immunoreactivity and a robust increase was observed at 72 h. Double-label immunohistochemical analysis for β1 integrin with neuronal (NeuN), microglial (Iba-1), astrocyte (GFAP), progenitor cell (Ng2) and blood vessel (collagen 4) markers showed that β1 integrin expression only localized to blood vessels. In vitro studies using cultured endothelial cells and a β1 integrin blocking antibody confirmed that β1 integrin is required for endothelial cell migration, proliferation and blood vessel formation. In vivo studies in the cerebral I/R model using the β1 integrin blocking antibody further confirmed that β1 integrin signaling is involved in vascular formation and recovery following ischemic stroke. Finally, we found that β1 integrin is critically involved in functional deficits and survival after a stroke. These results suggest that β1 integrin plays important roles in neurovascular remodelling and functional outcomes following stroke, and that targeting the β1 integrin signalling may provide a novel strategy for modulating angiogenesis in ischemic stroke and other pathological conditions. © 2009 Elsevier Inc