Effect of caspase-3 inhibitor on cerebral vasospasm after subarachnoid hemorrhage

Objective To observe the effect of early high-dose specific caspase-3 inhibitor on cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). Methods Twenty male New Zealand rabbits were equally randomized into 4 groups: ① control, injection of normal saline to the cisterna magna, ② SAH, ③ SAH treated with DMSO, and ④ SAH treated with z-DEVD-fmk (a specific Caspase-3 inhibitor). The rabbit SAH model was constructed by blood injection into the cisterna magna twice. The perfusion-fixation was performed for sacrifice of the rabbits on the 5th day after the second blood-injection in vivo and the basilar artery was taken. Immunohistochemical technique and TUNEL were used to observe the expression of caspase-3 and apoptosis of endothelial cells in the basilar artery. The cross-sectional area of each basilar arterial lumen was measured to evaluate the degree of cerebral vasospasm. Results Immunohistochemical technique showed that the expression of endothelial caspase-3 of the basilar artery was significantly lower in group SAH treated with z-DEVD-fmk than in group SAH and group SAH treated with DMSO (P0.05), and TUNEL revealed that apoptosis level of endothelial cells in group SAH treated with z-DEVD-fmk was significantly lower than in group SAH and group SAH treated with DMSO (P0.01). The cross-sectional areas of the basilar arterial lumen in group SAH and group SAH treated with DMSO were smaller than that of control group (P0.01), while those of group SAH treated with z-DEVD-fmk were larger than that of the group SAH and group SAH treated with DMSO (P0.01). Conclusion Early high dose specific caspase-3 inhibitor can decrease endothelial apoptosis in the basilar artery in rabbit SAH model, and relieve CVS after SAH.