Sex differences in stroke outcome correspond to rapid and severe changes in gut permeability in adult Sprague-Dawley rats.
Sex differences in stroke outcome correspond to rapid and severe changes in gut permeability in adult Sprague-Dawley rats.
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DOI：
10.1186/s13293-020-00352-1
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发表时间：
2021-01-15
影响因子：
7.9
通讯作者：
Sohrabji F
中科院分区：
文献类型：
--
作者：
El-Hakim Y;Mani KK;Eldouh A;Pandey S;Grimaldo MT;Dabney A;Pilla R;Sohrabji F
实验卒中结果的性别差异已被充分证明，例如成年男性有更大的梗死面积，卒中引起的死亡率增加，以及更严重的感觉运动障碍。最近有证据表明，肠道是中风的早期反应者，本研究验证了这样一种假设：与女性相比，男性在中风严重程度上的性别差异将伴随着肠道-血液屏障的快速和更大的渗透性和肠道生态失调。采用内皮素(ET)-1诱导的大脑中动脉闭塞（MCAo）治疗5-7月龄雄性和雌性Sprague-Dawley大鼠。在MCAo前和术后2天分别进行感觉运动测试。使用肠通透性生物标志物评估血清样本中的肠通透性，并使用大小分级右旋糖酐进行功能测定。对肠道进行组织学分析，采用H&E染色，对粘液进行周期性酸-希夫染色，对紧密连接蛋白ZO-1进行免疫组化。对中风前后的粪便样本进行细菌分类和短链脂肪酸（SCFAs）分析。中风后，男性表现出更高的死亡率，更严重的感觉运动障碍，血清中促炎细胞因子IL-17A、MCP-1和IL-5的水平高于女性。在男性中风的超急性期（< 2小时）和早期急性期（2天），右旋糖酐从肠道外渗到血液中，表明mcao诱导的肠道通透性迅速而严重。这伴随着急性期肠绒毛的形态异常和紧密连接蛋白ZO-1的失调。粪便16s测序显示，在中风急性期细菌多样性没有差异。预测模型显示，肠通透性标志物与急性感觉运动损伤和梗死体积相关。这些数据表明，肠道屏障的广泛渗漏与中风后严重的残疾有关，并表明加强这一屏障可能改善中风的预后。在线版本包含补充材料，可在10.1186/s13293-020-00352-1获得。
Sex differences in experimental stroke outcomes are well documented, such that adult males have a greater infarct volume, increased stroke-induced mortality, and more severe sensory-motor impairment. Based on recent evidence that the gut is an early responder to stroke, the present study tested the hypothesis that sex differences in stroke severity will be accompanied by rapid and greater permeability of the gut-blood barrier and gut dysbiosis in males as compared to females. Male and female Sprague-Dawley rats (5–7 months of age) were subject to endothelin (ET)-1-induced middle cerebral artery occlusion (MCAo). Sensory-motor tests were conducted pre- and 2 days after MCAo. Gut permeability was assessed in serum samples using biomarkers of gut permeability as well as functional assays using size-graded dextrans. Histological analysis of the gut was performed with H&E staining, periodic acid-Schiff for mucus, and immunohistochemistry for the tight junction protein, ZO-1. Fecal samples obtained pre- and post-stroke were analyzed for bacterial taxa and short-chain fatty acids (SCFAs). After stroke, males displayed greater mortality, worse sensory-motor deficit, and higher serum levels of proinflammatory cytokines IL-17A, MCP-1, and IL-5 as compared to females. MCAo-induced gut permeability was rapid and severe in males as indicated by dextran extravasation from the gut to the blood in the hyperacute (< 2 h) and early acute (2 days) phase of stroke. This was accompanied by dysmorphology of the gut villi and dysregulation of the tight junction protein ZO-1 in the acute phase. Fecal 16s sequencing showed no differences in bacterial diversity in the acute phase of stroke. Predictive modeling indicated that markers of gut permeability were associated with acute sensory-motor impairment and infarct volume. These data show that extensive leakiness of the gut barrier is associated with severe post-stroke disability and suggest that reinforcing this barrier may improve stroke outcomes. The online version contains supplementary material available at 10.1186/s13293-020-00352-1.
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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：
2.4
作者：
Bischoff SC;Barbara G;Buurman W;Ockhuizen T;Schulzke JD;Serino M;Tilg H;Watson A;Wells JM
通讯作者：
Wells JM
老年小鼠缺血性中风后T细胞免疫反应，肠道渗透性和结果的性别差异。
DOI：
10.1016/j.bbi.2020.02.001
发表时间：
2020-07
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Ahnstedt H;Patrizz A;Chauhan A;Roy-O'Reilly M;Furr JW;Spychala MS;D'Aigle J;Blixt FW;Zhu L;Bravo Alegria J;McCullough LD
通讯作者：
McCullough LD
影响因子：
14.2
作者：
Groschwitz, Katherine R.;Hogan, Simon P.
通讯作者：
Hogan, Simon P.
影响因子：
1.4
作者：
Apprill, Amy;McNally, Sean;Weber, Laura
通讯作者：
Weber, Laura