Effects of gap junctional blockers on cerebral vasospasm after subarachnoid hemorrhage in rabbits

摘要

The role of gap junctional communication in the coordination of vascular behavior has been well established experimentally. The aim of this study was to investigate whether the gap junctional blockers would inhibit cerebral vasospasm after experimental subarachnoid hemorrhage (SAH). We used the double-hemorrhage model of SAH with injection of autologous arterial blood into the cisterna magna on days 1 and 2. Octanol or carbenoxolone was administered intracisternally on day 3, and repeated on days 4 and 5. Angiography was performed before (day 0) and 7 days after (day 7) SAH, and the diameter of the basilar artery was measured. Paraffin blocks of brain tissues were prepared and sectioned for hematoxylin and eosin staining for morphologic analysis. Arterial narrowing in SAH + octanol group and SAH + carbenoxolone group at day 7 was significantly less than that in SAH-only group and each SAH + vehicle group, respectively. Less morphologic changes in SAH + octanol group and SAH + carbenoxolone group were observed when compared to that in SAH-only group and each SAH + vehicle group. Western blotting showed that carbenoxolone down-regulated C×43 protein expression in the BA, which in the SAH-only group was significantly higher than that of the normal group. Gap junction blockers attenuate the experimental cerebral vasospasm and down-regulate the increase in expression of C×43 protein after SAH in rabbits. These data suggest that gap junctions play an important role in the development of cerebral vasospasm.