抄録
Traumatic brain injury (TBI) is a fetal damage to central nervous tissue (CNS) resulted from an external force to head by traffic accidents or severe sports. One of TBI-induced severe pathogenesis is blood-brain barrier (BBB) disruption which causes brain edema and inflammatory damages. Thus, recovery of BBB disruption must be a beneficial strategy for TBI. We previously confirmed that BQ788, an endothelin ETB receptor antagonist recovered TBI-induced BBB disruption in mice. In this study, angiopoietin-1 (Ang-1) was focused as a target for beneficial effects of BQ788 on TBI-induced BBB disruption. As a model of TBI, fluid percussion injury (FPI) was performed by hydraulic impact on mouse dura mater. BQ788 (15 nmol/day) or recombinant Ang-1 were repeatedly administrated into lateral cerebroventricle from 2 to 5 days after FPI. To evaluate BBB disruption, extravasation of Evans blue was examined in mouse cerebrum. Expressions of brain endothelin-1 (ET-1) and Ang-1 were measured by Real-time PCR. Expressions of tight junction proteins (claudin-5, occludin and zonula occludens-1) were observed by western blot. After FPI, BBB disruption was observed in mouse injured hemisphere in 2 to 5 day and recovered in 7 to 10 day after FPI. Expression of brain ET-1 was increased in 2 to 5 day after FPI while brain Ang-1 was increased in 7 to 10 day after FPI. BQ788 ameliorated FPI-induced BBB disruption and increased Ang-1 expression in 5 day after FPI. Recombinant Ang-1 also recovered FPI-induce BBB disruption. Moreover, BQ788 and recombinant Ang-1 reversed FPI-induced decreases of tight junction proteins. These results suggest that blockade of ETB receptor promotes recovery of BBB disruption by increase of Ang-1 after TBI.
