Sex differences in T cell immune responses, gut permeability and outcome after ischemic stroke in aged mice.
Sex differences in T cell immune responses, gut permeability and outcome after ischemic stroke in aged mice.
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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
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发表时间：
2020-07
期刊：
影响因子：
--
通讯作者：
McCullough LD
中科院分区：
文献类型：
--
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
中风是一种两性异形疾病。虽然女性中风死亡人数更多，但最近的数据显示，在调整年龄和中风前功能状态后，男性的死亡率更高。免疫反应是卒中结局的关键决定因素，可能因性别而异。这项研究检查了中枢和外周T细胞免疫反应的性别差异，对肠道通透性和微生物群多样性的全身影响以及老年小鼠中风后的行为结果。我们假设老年动物对中风的免疫反应存在性别差异。对C57 BL/6 N小鼠（20-22个月）进行60分钟的大脑中动脉闭塞或假手术。在中风后第3、7和15天（d）通过流式细胞术定量脑和血液中的T细胞。外周对肠道通透性和微生物群多样性以及神经功能的影响在卒中后14天和21天（认知功能）进行了评估。脑胶质细胞酸性蛋白（GFAP）表达在卒中后42天进行评估。男性的死亡率（50% vs 14%，p<0.05）和出血性转化率（44% vs 0%）显著高于女性。3d时梗死面积无差异。在外周，中风在d3时诱导雄性中FITC-葡聚糖的更大的肠道渗透性（p<0.05），以及雄性中微生物群多样性的不可逆改变。亚急性期后，两种性别的大脑中CD 4+和CD 8 + T细胞均呈时间依赖性增加，其中雄性在第15天的CD 8 + T细胞和调节性T细胞水平显着较高（p<0.01）。当通过角不对称测试评估时，老年男性表现出更大的神经功能缺损，直至第5天，感觉运动功能受损，直至第15天（分别为p<0.001和p<0.01）。在第21天，在雄性动物中观察到更大的认知下降趋势。中风后42天，在男性和女性中，缺血半球中GFAP表达增加，表明星形胶质细胞活化和胶质增生。我们的研究结果表明，尽管有类似的初始缺血性脑损伤，但老年雄性小鼠在中风后的亚急性期对肠道和持续的中枢神经炎症有更大的外周影响。
Stroke is a sexually dimorphic disease. While women account for more stroke deaths, recent data show that after adjusting for age and pre-stroke functional status, mortality is higher in men. Immune responses are key determinants of stroke outcome and may differ by sex. This study examined sex differences in central and peripheral T cell immune responses, systemic effects on gut permeability and microbiota diversity and behavioral outcomes after stroke in aged mice. We hypothesized that there are sex differences in the immune response to stroke in aged animals. C57BL/6N mice (20-22 months) were subjected to 60 min middle cerebral artery occlusion, or sham surgery. T cells were quantified in brain and blood at 3, 7 and 15 days (d) post-stroke by flow cytometry. Peripheral effects on gut permeability and microbiota diversity, as well as neurological function were assessed up to 14d, and at 21d (cognitive function) post-stroke. Brain glial fibrillary acidic protein (GFAP) expression was evaluated at 42d post-stroke. Mortality (50% vs 14%, p<0.05) and hemorrhagic transformation (44% vs 0%) were significantly higher in males than in females. No difference in infarct size at 3d were observed. Peripherally, stroke induced greater gut permeability of FITC-dextran in males at d3 (p<0.05), and non-reversible alterations in microbiota diversity in males. Following the sub-acute phase, both sexes demonstrated a time-dependent increase of CD4+ and CD8+ T cells in the brain, with significantly higher levels of CD8+ T cells and Regulatory T cells in males at d15 (p<0.01). Aged males demonstrated greater neurological deficits up to d5 and impaired sensorimotor function up to d15 when assessed by the corner asymmetry test (p<0.001 and p<0.01, respectively). A trend in greater cognitive decline was observed at d21 in males. Increased GFAP expression in the ischemic hemisphere, indicating astroglial activation and gliosis, was demonstrated in both males and females 42d post-stroke. Our findings indicate that despite a similar initial ischemic brain injury, aged male mice experience greater peripheral effects on the gut and ongoing central neuroinflammation past the sub-acute phase after stroke.
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影响因子：
3.3
作者：
Dotson, Abby L.;Wang, Jianming;Saugstad, Julie;Murphy, Stephanie J.;Offner, Halina
通讯作者：
Offner, Halina
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：
37.8
作者：
Go AS;Mozaffarian D;Roger VL;Benjamin EJ;Berry JD;Blaha MJ;Dai S;Ford ES;Fox CS;Franco S;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Huffman MD;Judd SE;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Mackey RH;Magid DJ;Marcus GM;Marelli A;Matchar DB;McGuire DK;Mohler ER 3rd;Moy CS;Mussolino ME;Neumar RW;Nichol G;Pandey DK;Paynter NP;Reeves MJ;Sorlie PD;Stein J;Towfighi A;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者：
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
影响因子：
8.3
作者：
BEDERSON, JB;PITTS, LH;BARTKOWSKI, H
通讯作者：
BARTKOWSKI, H
影响因子：
8.3
作者：
Alkayed, NJ;Murphy, SJ;Hurn, PD
通讯作者：
Hurn, PD