Experimental Study On The Effect Of Combined Use Of Insulin And Vitamin C In Cerebral Vasospasm After Subarachnoid Hemorrhage

Background: Cerebral vasospasm(CVS) is a common, formidable, and potentially devastating complication in patients who have sustained subarachnoid hemorrhage (SAH). Despite intensive research efforts, cerebral vasospasm remains incompletely understood from both the pathogenic and therapeutic perspectives. At present, no consistently efficacious and ubiquitously applied preventive and therapeutic measures are available in clinical practice. Recently, insulin's vascular actions are ardently researched. Once insulin is binding with insulin receptor on vascular endothelial cell, two downstream signaling passageways will be activated and respectively lead endothelial ceils to release nitric oxide (NO) and endothelin-1 (ET-I) which are both main substance regulating vasoconstriction and vasodilatation. This study's aim is to illustrate the effect of insulin in vasculature based on treatment of CVS after SAH with Vitamin C and insulin together.In the stage, 35 rabbits were assigned randomly to 4 experimental groups: (1) control group (n=5), injected 1.5ml normal saline instead of blood into the cisterna magna; (2) SAH group only (n=10), no treatment after twice hemorrhage; (3)SAH＋insulin(n=10), treatment with insulin only; (4) SAH＋Vitamin C＋insulin (n=10), treatment with vitamin C and insulin together. Treatment was initiated 30 minutes after the first injecting blood. On the 5th day, the basilar arteries of animals with its adjacent parts of brain tissue were dissociated and stored in 10% neutral formalin solution. All basilar arteries specimen were sent to pathologic department to fix, imbed in paraffin, slice and then stain with HE. Cross-cut area of the basilar arterial lumen was measured to evaluate the efficacy of insulin in attenuating cerebral vasospasm. In addition, expression of Insulin receptors in endothelial cells was unfolded by staining with immunohistochemical technique. Result The value of the cross sectional area of the arterial lumen in the 2nd group and the 3th group were 236486.37±8721.3gm~2 and 245787.8±23878.1gm~2 respectively, which were significantly decreased compared with that of control group (462107.90±42999.4μm~2), P＜0.001. The SAH＋Vitamin C＋insulin group was 410688.9±19618.13μtm~2 and there was no significant difference compared with the control group (P=0.187). Insulin receptors were detected diffusely in the vascular endothelial cell layer in the control group and the 4th group, but it was decreased significantly or even absent in the SAH group and the treatment group with insulin alone. Conclusion Combined use of vitamin C and insulin, not insulin alone, may effectively improve the spastic cerebral vasculature.