Vitamin D(3) Supplementation Reduces Subsequent Brain Injury and Inflammation Associated with Ischemic Stroke.
Vitamin D(3) Supplementation Reduces Subsequent Brain Injury and Inflammation Associated with Ischemic Stroke.
复制标题
DOI：
10.1007/s12017-018-8484-z
复制
发表时间：
2018-03
影响因子：
3.5
通讯作者：
Sobey CG
中科院分区：
文献类型：
--
作者：
Evans MA;Kim HA;Ling YH;Uong S;Vinh A;De Silva TM;Arumugam TV;Clarkson AN;Zosky GR;Drummond GR;Broughton BRS;Sobey CG
急性炎症可加重缺血性卒中后的脑损伤。除了其在钙代谢中的良好表征的作用之外，人们越来越认识到维生素D的活性形式1，25-二羟基维生素D3（1，25-VitD 3）具有有效的免疫调节特性。在这里，我们的目的是确定1，25-VitD 3补充剂是否可以减少缺血性卒中后随后的脑损伤和相关炎症。将雄性C57 B16小鼠随机分配以在中风前腹膜内施用1，25-VitD 3（100 ng/kg/天）或媒介物5天。通过大脑中动脉闭塞1小时，然后再灌注23小时诱导卒中。在卒中后24小时，我们评估了梗死体积、功能缺陷、炎症介质的表达和浸润免疫细胞的数量。与载体相比，补充1，25-VitD 3使梗塞体积减少50%。在接受1，25-VitD 3的小鼠的脑中，促炎介质IL-6、IL-1β、IL-23 α、TGF-β和NADPH氧化酶-2的表达相对于载体减少。补充1，25-VitD 3的小鼠脑中调节性T细胞标志物Foxp 3的表达高于补充溶剂的小鼠，而转录因子ROR-γ的表达降低，表明Th 17/γδ T细胞应答降低。免疫组织化学表明，类似数量的中性粒细胞和T细胞存在于1，25-VitD 3和车辆补充小鼠的缺血半球。在这个早期时间点，运动功能的损害也没有差异。这些数据表明，事先给予外源性维生素D，甚至维生素D-充满小鼠，可以减弱梗死的发展，并发挥急性抗炎作用，在缺血和再灌注脑。本文的在线版本（10.1007/s12017-018-8484-z）包含补充材料，可供授权用户使用。
Acute inflammation can exacerbate brain injury after ischemic stroke. Beyond its well-characterized role in calcium metabolism, it is becoming increasingly appreciated that the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25-VitD3), has potent immunomodulatory properties. Here, we aimed to determine whether 1,25-VitD3 supplementation could reduce subsequent brain injury and associated inflammation after ischemic stroke. Male C57Bl6 mice were randomly assigned to be administered either 1,25-VitD3 (100 ng/kg/day) or vehicle i.p. for 5 day prior to stroke. Stroke was induced via middle cerebral artery occlusion for 1 h followed by 23 h reperfusion. At 24 h post-stroke, we assessed infarct volume, functional deficit, expression of inflammatory mediators and numbers of infiltrating immune cells. Supplementation with 1,25-VitD3 reduced infarct volume by 50% compared to vehicle. Expression of pro-inflammatory mediators IL-6, IL-1β, IL-23a, TGF-β and NADPH oxidase-2 was reduced in brains of mice that received 1,25-VitD3 versus vehicle. Brain expression of the T regulatory cell marker, Foxp3, was higher in mice supplemented with 1,25-VitD3 versus vehicle, while expression of the transcription factor, ROR-γ, was decreased, suggestive of a reduced Th17/γδ T cell response. Immunohistochemistry indicated that similar numbers of neutrophils and T cells were present in the ischemic hemispheres of 1,25-VitD3- and vehicle-supplemented mice. At this early time point, there were also no differences in the impairment of motor function. These data indicate that prior administration of exogenous vitamin D, even to vitamin D-replete mice, can attenuate infarct development and exert acute anti-inflammatory actions in the ischemic and reperfused brain. The online version of this article (10.1007/s12017-018-8484-z) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
82.9
作者：
Benakis C;Brea D;Caballero S;Faraco G;Moore J;Murphy M;Sita G;Racchumi G;Ling L;Pamer EG;Iadecola C;Anrather J
通讯作者：
Anrather J
影响因子：
3.7
作者：
De Silva TM;Brait VH;Drummond GR;Sobey CG;Miller AA
通讯作者：
Miller AA
DOI：
10.1073/pnas.1306072110
发表时间：
2013-12-24
影响因子：
11.1
作者：
Grishkan, Inna V.;Fairchild, Amanda N.;Gocke, Anne R.
通讯作者：
Gocke, Anne R.
影响因子：
3.4
作者：
Fu, Jun;Xue, Rui;Ran, Ran
通讯作者：
Ran, Ran
影响因子：
20.3
作者：
Gelderblom, Mathias;Weymar, Anna;Magnus, Tim
通讯作者：
Magnus, Tim