Estradiol and G1 reduce infarct size and improve immunosuppression after experimental stroke.
Estradiol and G1 reduce infarct size and improve immunosuppression after experimental stroke.
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DOI：
10.4049/jimmunol.0902339
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发表时间：
2010-04-15
期刊：
影响因子：
--
通讯作者：
Hurn PD
中科院分区：
文献类型：
--
作者：
Zhang B;Subramanian S;Dziennis S;Jia J;Uchida M;Akiyoshi K;Migliati E;Lewis AD;Vandenbark AA;Offner H;Hurn PD
成年女性中风风险和严重程度的降低被认为取决于雌激素（一种众所周知的神经保护剂和免疫调节剂）的正常内源性水平。在雄性小鼠中，实验性中风诱导外周免疫系统的免疫抑制，其特征在于脾脏大小和细胞数量减少以及细胞因子和趋化因子表达降低。然而，尚未在雌性小鼠中评价卒中诱导的免疫抑制。为了验证雌激素（E2）缺乏会加重女性局灶性卒中后免疫抑制的假设，我们评估了大脑中动脉闭塞对卵巢切除小鼠的梗死面积以及外周和中枢神经系统免疫应答的影响，这些小鼠接受或不接受持续的、控制水平的17-β-E2皮下注射。植入物或推定的膜雌激素受体激动剂，G1。E2-和G1-替代减少梗死体积和部分恢复脾细胞数量。此外，E2替代增加了脾细胞对抗CD 3/CD 28 Ab刺激的反应，并使细胞因子、趋化因子和趋化因子受体的异常mRNA表达以及在E2缺乏动物中观察到的CD 4 + CD 25 + FoxP 3 + T调节细胞的百分比正常化。E2替代后外周免疫的这些有益变化伴随着趋化因子MIP-2表达的显著减少，以及受损大脑半球中CCR 7表达的40倍增加。这些结果首次表明，在卵巢切除雌性小鼠中，E2替代可改善中风诱导的外周免疫抑制。
Reduced risk and severity of stroke in adult females is thought to depend on normal endogenous levels of estrogen, a well-known neuroprotectant and immunomodulator. In male mice, experimental stroke induces immunosuppression of the peripheral immune system, characterized by a reduction in spleen size and cell numbers and decreased cytokine and chemokine expression. However, stroke-induced immunosuppression has not been evaluated in female mice. To test the hypothesis that estradiol (E2) deficiency exacerbates immunosuppression after focal stroke in females, we evaluated the effect of middle cerebral artery occlusion on infarct size and peripheral and CNS immune responses in ovariectomized mice with or without sustained, controlled levels of 17-β–E2 administered by s.c. implant or the putative membrane estrogen receptor agonist, G1. Both E2- and G1-replacement decreased infarct volume and partially restored splenocyte numbers. Moreover, E2-replacement increased splenocyte proliferation in response to stimulation with anti-CD3/CD28 Abs and normalized aberrant mRNA expression for cytokines, chemokines, and chemokine receptors and percentage of CD4+CD25+FoxP3+ T regulatory cells observed in E2-deficient animals. These beneficial changes in peripheral immunity after E2 replacement were accompanied by a profound reduction in expression of the chemokine, MIP-2, and a 40-fold increased expression of CCR7 in the lesioned brain hemisphere. These results demonstrate for the first time that E2 replacement in ovariectomized female mice improves stroke-induced peripheral immunosuppression.
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影响因子：
8.6
作者：
Ito, A;Buenafe, AC;Offner, H
通讯作者：
Offner, H
影响因子：
8.3
作者：
Alkayed, NJ;Murphy, SJ;Hurn, PD
通讯作者：
Hurn, PD
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3.6
作者：
Ebert, LA;Schaerli, P;Moser, B
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82.9
作者：
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通讯作者：
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影响因子：
8.3
作者：
Liesz, Arthur;Hagmann, Sebastien;Veltkamp, Roland
通讯作者：
Veltkamp, Roland