Rapid Loss of Microvascular Integrin Expression during Focal Brain Ischemia Reflects Neuron Injury

Abstract

The integrity of cerebral microvessels requires the close apposition of the endothelium to the astrocyte endfeet. Integrins α1β1 and α6β4 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 α1β1 and α6β4 expression were examined in the basal ganglia of 17 primates. Integrin subunits α1 and β1 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 α1 and β1 subunits and integrin α6β4 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 β1 mRNA on microvessels increased significantly in the Ic/Ip border and in multiple circular subregions within Ic. Microvascular integrin α1β1 and integrin α6β4 expression are rapidly and coordinately lost in Ic after MCAO. With loss of integrin α1β1, multiple regions of microvascular β1 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.