Combinatorial administration of insulin and vitamin C alleviates the cerebral vasospasm after experimental subarachnoid hemorrhage in rabbit

Background: Cerebral vasospasm (CVS) is a common serious complication after the spontaneous subarachnoid hemorrhage (SAH). Despite recent advances in medical and surgical treatments, the 30-day mortality rate of SAH remains high, and there is lack of especially effective clinical treatment to alleviate and improve CVS. The present study has investigated the therapeutic effect of insulin and vitamin C on CVS after SAH. Results: Five days after SAH, there is obvious basilar artery spasm in SAH group, whose average vascular cross-sectional area (233,099 +/- 16,750 mu m(2)) is significantly smaller than that in control group (462,128 +/- 74,756 mu m(2)), which is also significantly different from those in SAH + insulin group (221,114 +/- 43,457 mu m(2)) and SAH + vitamin C group (237,820 +/- 21,703 mu m(2)). SAH + insulin + vitamin C group shows no evident vasospasm and maintains a vascular cross-sectional area of 425,530 +/- 45,503 mu m(2), which is significantly different from that in SAH group. Insulin receptor alpha (InR alpha) expression is significantly downregulated in the vascular endothelial cells of SAH, SAH + insulin, and SAH + vitamin C groups (P < 0.01) but remains unchanged in vascular endothelial cells of SAH + insulin + vitamin C group (P > 0.05). Five days after SAH, serum and cerebrospinal fluid NO levels in SAH, SAH + insulin, and SAH + vitamin C groups decrease significantly (P < 0.01) compared to that in control group, whereas the reduction is not evident in SAH + insulin + vitamin C group (P > 0.05). Conclusion: Combinatorial treatment with insulin and vitamin C has effectively relieved the CVS after SAH in rabbit, possibly through increasing the InRa expression and NO level, whereas treatment with insulin or vitamin C alone fails to do so.