Chronic hypoperfusion increases claudin-3 immunoreactivity in rat brain

Abstract

Chronic hypoperfusion-induced changes in blood–brain barrier (BBB) tight junction components have not been well studied. In the present study, we investigated the temporal profiles of claudin-3 (a BBB tight junction element) and myleoperoxidase (MPO, a marker of neutrophil infiltration) in the cortical and thalamic regions of rat brain subjected to chronic cerebral hypoperfusion. Chronic cerebral hypoperfusion was induced by an occlusion of two common carotid arteries and the immunoreactivity of claudin-3 or MPO was determined at 1, 2, 3, or 6 weeks after the occlusion. A typical pattern of BBB breakdown was observed from 2 weeks of the occlusion in cortical and thalamic regions based on Evans Blue leakage. Claudin-3 immunoreactivity was increased only in cortical regions after 2 weeks of occlusion. However, after 3 weeks of occlusion, marked increases in claudin-3 immunoreactivity were observed in both cortical and thalamic regions ( P < 0.05), which persisted for at least 6 weeks after the occlusion despite a slight reduction. In contrast, MPO immunoreactivity was increased only in the thalamic regions after 2 weeks of occlusion. But the pattern of MPO immunoreactivity at 3 and 6 weeks after the occlusion was same as claudin-3. At these time points, MPO immunoreactivity was significantly increased in both cortical and thalamic regions ( P < 0.05). These results show that chronic cerebral hypoperfusion increases the immunoreactivity of claudin-3 and neutrophil infiltration in cortical and thalamic regions of the brain, and demonstrate changes in BBB tight junction status during chronic cerebral hypoperfusion.