Vitamin D Deficiency Exacerbates Experimental Stroke Injury and Dysregulates Ischemia-Induced Inflammation in Adult Rats
Vitamin D Deficiency Exacerbates Experimental Stroke Injury and Dysregulates Ischemia-Induced Inflammation in Adult Rats
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DOI：
10.1210/en.2011-1783
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发表时间：
2012-05-01
期刊：
影响因子：
4.8
通讯作者：
Sohrabji, Farida
中科院分区：
文献类型：
--
作者：
Balden, Robyn;Selvamani, Amutha;Sohrabji, Farida
维生素D缺乏症（VDD）很普遍，被认为是心血管疾病和中风的危险因素。维生素D水平低预示着人类中风和更致命的中风，而维生素D补充剂与全因死亡率的降低有关。由于VDD与其他合并症同时发生，这些合并症也是卒中的独立危险因素，因此本研究考察了VDD对大鼠卒中严重程度的具体影响。成年雌性大鼠分别饲喂对照组或VDD日粮8周，随后进行大脑中动脉闭塞。VDD饮食将循环维生素D水平降低到对照组的五分之一（22%）。饲喂VDD的动物脑皮层和纹状体梗死体积显著增大，感觉运动行为测试表明，VDD动物脑卒中后行为障碍比对照组更严重。研究还发现，VDD动物血浆和缺血半球的神经保护激素igf - 1水平明显较低。细胞因子分析表明，VDD显著降低缺血脑组织中IL-1 α、IL-1 β、IL-2、IL-4、ifn - γ和IL-10的表达。然而，缺血诱导的IL-6上调在VDD动物中显著升高。在另一项单独的实验中，对急性维生素D治疗的治疗潜力进行了评估，动物在中风后4小时注射维生素D，此后每24小时注射一次。急性维生素D治疗没有改善梗死面积或行为表现。我们的数据表明，VDD加重了中风的严重程度，包括炎症反应的失调以及已知的神经保护剂如IGF-I的抑制。（内分泌学153:2420-2435,2012）
Vitamin D deficiency (VDD) is widespread and considered a risk factor for cardiovascular disease and stroke. Low vitamin D levels are predictive for stroke and more fatal strokes in humans, whereas vitamin D supplements are associated with decreased risk of all-cause mortality. Because VDD occurs with other comorbid conditions that are also independent risk factors for stroke, this study examined the specific effect of VDD on stroke severity in rats. Adult female rats were fed control or VDD diet for 8 wk and were subject to middle cerebral artery occlusion thereafter. The VDD diet reduced circulating vitamin D levels to one fifth (22%) of that observed in rats fed control chow. Cortical and striatal infarct volumes in animals fed VDD diet were significantly larger, and sensorimotor behavioral testing indicated that VDD animals had more severe poststroke behavioral impairment than controls. VDD animals were also found to have significantly lower levels of the neuroprotective hormone IGF-I in plasma and the ischemic hemisphere. Cytokine analysis indicated that VDD significantly reduced IL-1 alpha, IL-1 beta, IL-2, IL-4, IFN-gamma, and IL-10 expression in ischemic brain tissue. However, ischemia-induced IL-6 up-regulation was significantly higher in VDD animals. In a separate experiment, the therapeutic potential of acute vitamin D treatments was evaluated, where animals received vitamin D injections 4 h after stroke and every 24 h thereafter. Acute vitamin D treatment did not improve infarct volume or behavioral performance. Our data indicate that VDD exacerbates stroke severity, involving both a dysregulation of the inflammatory response as well as suppression of known neuroprotectants such as IGF-I. (Endocrinology 153: 2420-2435, 2012)