Rapid loss of microvascular integrin expression during focal brain ischemia reflects neuron injury

The integrity of cerebral microvessels requires the close apposition of the endothelium to the astrocyte endfeet. Integrins ol,P, and ol,P, are cellular matrix receptors that may contribute to cerebral microvascular integrity. It has been hypothesized that focal ischemia alters integrin expression in a characteristic time-dependent manner consistent with neuron injury. The effects of middle cerebral artery occlusion (MCAO) and various periods of reperfusion on microvasclar integrin alpha (1)beta (1) and alpha (6)beta (4) expression were examined in the basal ganglia of 17 primates. Integrin subunits alpha (1) and beta (1) colocalized with the endothelial cell antigen CD31 in nonischemic microvessels and with glial fibrillary acidic protein on astrocyte fibers. Rapid, simultaneous, and significant disappearance of both integrin alpha (1), and beta (1) subunits and integrin alpha (6)beta (4) occurred by 2 hours MCAO, which was greatest in the region of neuron injury (ischemic core, Ic), and progressively less in the peripheral (Ip) and nonischemic regions (N). Transcription of subunit beta (1) mRNA on microvessels increased significantly in the Ic/Ip border and in multiple circular subregions within Ic. Microvascular integrin a,P, and integrin a,P, expression are rapidly and coordinately lost in Ic after MCAO. With loss of integrin oc,P,, multiple regions of microvascular p, mRNA up-regulation within Ic suggest that microvessel responses to focal ischemia are dynamic, and that multiple cores, not a single core, are generated. These changes imply that microvascular integrity is modified in a heterogeneous, but ordered pattern.