Rapid Disruption of an Astrocyte Interaction With the Extracellular Matrix Mediated by Integrin α 6 β 4 During Focal Cerebral Ischemia/Reperfusion

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Abstract
Background and Purpose Integrins participate in cerebral microvascular integrity and signaling during focal ischemia/reperfusion. The integrin subunits α1, α6, and β1 are distributed identically on normal cerebral microvessels. Studies in epithelium indicate that integrin α6β4, which interacts with laminin-5 in the basal lamina/extracellular matrix, is unique. This study describes the exact location of α6, β4, and α6β4 and that their responses in focal cerebral ischemia are relevant to astrocyte-matrix interactions. Methods The effect of middle cerebral artery occlusion and subsequent reperfusion on the microvascular expression of α6β4 and laminin-5 in regions of cellular injury (dUTP incorporation) was examined in 15 nonhuman primates. Well-characterized antibodies against human α6, β4, α6β4, laminin-5 and laminin-1, endothelial CD31, and vascular markers were measured with computerized video imaging and laser confocal microscopy. Results Integrin α6β4 was localized on astrocytes where it connects with t...