Sasani Mehdi, Yazgan Burak, Celebi Irfan, Aytan Nurgul, Catalgol Betul, Oktenoglu Tunc, Kaner Tuncay, Ozer Nesrin Kartal, Ozer Ali Fahir
Department of Neurosurgery, American Hospital, Istanbul, Turkey.
Surg Neurol Int. 2011 Mar 14;2:29. doi: 10.4103/2152-7806.77600.
Aneurysm rupture results in subarachnoid hemorrhage (SAH) with subsequent vasospasm in the cerebral and cerebellar major arteries. In recent years, there has been increasing evidence that hypercholesterolemia plays a role in the pathology of SAH. It is known that hypercholesterolemia is one of the major risk factors for the development of atherosclerosis. Among the factors that have been found to retard the development of atherosclerosis is the intake of a sufficient amount of Vitamin E. An inverse association between serum Vitamin E and coronary heart disease mortality has been demonstrated in epidemiologic studies. Therefore, we tested, in an established model of enhanced cholesterol feed in rabbits, the effects of hypercholesterolemia on vasospasm after SAH by using computed tomography (CT) angiograms of the rabbit basilar artery; in addition, we tested the effects of Vitamin E on these conditions, which have not been studied up to now.
In this study rabbits were divided into 3 major groups: control, cholesterol fed, and cholesterol + Vitamin E fed. Hypercholesterolemia was induced by a 2% cholesterol-containing diet. Three rabbit groups were fed rabbit diet; one group was fed a diet that also contained 2% cholesterol and another group was fed a diet containing 2% cholesterol and they received i.m. injections of 50 mg/kg of Vitamin E. After 8 weeks, SAH was induced by the double-hemorrhage method and distilled water was injected into cisterna magna. Blood was taken to measure serum cholesterol and Vitamin E levels. Basilar artery samples were taken for microscopic examination. CT angiography and measurement of basilar artery diameter were performed at days 0 and 3 after SAH.
Two percent cholesterol diet supplementation for 8 weeks resulted in a significant increase in serum cholesterol levels. Light microscopic analysis of basilar artery of hypercholesterolemic rabbits showed disturbances in the subendothelial and medial layers, degeneration of elastic fibers in the medial layer from endothelial cell desquamation, and a reduction of waves in the endothelial layer. However, the cholesterol + Vitamin E group did not exhibit these changes. The mean diameter of the basilar artery after SAH induction in the cholesterol-treated group was decreased 47% compared with the mean diameter of the control group. This value was less affected in cholesterol + Vitamin E-treated rabbits, which decreased 18% compared with the mean diameter of the control group.
Hypercholesterolemia-related changes in the basilar artery aggravate vasospasm after SAH. Adding Vitamin E to cholesterol-treated rabbits decreased the degree of vasospasm following SAH in the rabbit basilar artery SAH model. We suggest that Vitamin E supplements and a low cholesterol diet may potentially diminish SAH complicated by vasospasm in high-risk patients.
动脉瘤破裂会导致蛛网膜下腔出血（SAH），随后大脑和小脑的主要动脉会发生血管痉挛。近年来，越来越多的证据表明高胆固醇血症在SAH的病理过程中起作用。众所周知，高胆固醇血症是动脉粥样硬化发展的主要危险因素之一。在已发现的延缓动脉粥样硬化发展的因素中，摄入足够量的维生素E是其中之一。流行病学研究表明血清维生素E与冠心病死亡率之间存在负相关。因此，我们在已建立的家兔高胆固醇喂养模型中，通过兔基底动脉的计算机断层扫描（CT）血管造影来测试高胆固醇血症对SAH后血管痉挛的影响；此外，我们还测试了维生素E对这些目前尚未研究的情况的影响。
在本研究中，家兔被分为3个主要组：对照组、胆固醇喂养组和胆固醇+维生素E喂养组。通过含2%胆固醇的饮食诱导高胆固醇血症。三组家兔喂养兔饲料；一组喂养也含2%胆固醇的饲料，另一组喂养含2%胆固醇的饲料并肌肉注射50mg/kg的维生素E。8周后，采用双次出血法诱导SAH，并向枕大池注入蒸馏水。取血测量血清胆固醇和维生素E水平。取基底动脉样本进行显微镜检查。在SAH后第0天和第3天进行CT血管造影并测量基底动脉直径。
补充2%胆固醇饮食8周导致血清胆固醇水平显著升高。对高胆固醇血症家兔基底动脉的光镜分析显示内皮下层和中层出现紊乱，中层弹性纤维因内皮细胞剥脱而变性，内皮细胞层波浪减少。然而，胆固醇+维生素E组未出现这些变化。胆固醇治疗组诱导SAH后基底动脉的平均直径与对照组相比降低了47%。在胆固醇+维生素E治疗的家兔中，该值受影响较小，与对照组平均直径相比降低了18%。
基底动脉中与高胆固醇血症相关的变化会加重SAH后的血管痉挛。在胆固醇治疗的家兔中添加维生素E可降低兔基底动脉SAH模型中SAH后血管痉挛的程度。我们建议补充维生素E和低胆固醇饮食可能会减少高危患者并发血管痉挛的SAH。
