Suppr超能文献

雌二醇和 G1 可减少实验性中风后的梗死面积并改善免疫抑制。

Estradiol and G1 reduce infarct size and improve immunosuppression after experimental stroke.

机构信息

Department of Anesthesiology and Peri-Operative Medicine, Oregon Health and Science University, Portland, OR 97239-3098, USA

出版信息

J Immunol. 2010 Apr 15;184(8):4087-94. doi: 10.4049/jimmunol.0902339. Epub 2010 Mar 19.

Abstract

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-beta-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.

摘要

女性中风风险和严重程度降低被认为依赖于正常内源性雌激素水平,雌激素是一种众所周知的神经保护剂和免疫调节剂。在雄性小鼠中,实验性中风会导致外周免疫系统的免疫抑制,表现为脾脏缩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估中风诱导的免疫抑制。为了验证雌激素(E2)缺乏会加剧雌性小鼠局灶性中风后免疫抑制的假设,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免疫反应的影响,这些小鼠通过皮下植入或潜在的膜雌激素受体激动剂 G1 持续、受控水平地给予 17-β-E2。E2 和 G1 替代都减少了梗死体积并部分恢复了脾细胞数量。此外,E2 替代增加了对抗 CD3/CD28 Abs 刺激的脾细胞增殖,并使 E2 缺乏动物中观察到的细胞因子、趋化因子和趋化因子受体以及 CD4(+)CD25(+)FoxP3(+)T 调节细胞的异常 mRNA 表达正常化。E2 替代后外周免疫的这些有益变化伴随着趋化因子 MIP-2 的表达显著降低和损伤大脑半球中 CCR7 的表达增加 40 倍。这些结果首次表明,在卵巢切除的雌性小鼠中补充 E2 可改善中风引起的外周免疫抑制。

相似文献

1
Estradiol and G1 reduce infarct size and improve immunosuppression after experimental stroke.
J Immunol. 2010 Apr 15;184(8):4087-94. doi: 10.4049/jimmunol.0902339. Epub 2010 Mar 19.
3
Role of dihydrotestosterone in post-stroke peripheral immunosuppression after cerebral ischemia.
Brain Behav Immun. 2011 May;25(4):685-95. doi: 10.1016/j.bbi.2011.01.009. Epub 2011 Jan 22.
4
The loss of estrogen efficacy against cerebral ischemia in aged postmenopausal female mice.
Neurosci Lett. 2014 Jan 13;558:115-9. doi: 10.1016/j.neulet.2013.11.007. Epub 2013 Nov 15.
8
Induction of regulatory T cells by physiological level estrogen.
J Cell Physiol. 2008 Feb;214(2):456-64. doi: 10.1002/jcp.21221.
9
GPR 30 reduces myocardial infarct area and fibrosis in female ovariectomized mice by activating the PI3K/AKT pathway.
Life Sci. 2019 Jun 1;226:22-32. doi: 10.1016/j.lfs.2019.03.049. Epub 2019 Mar 21.

引用本文的文献

1
G-Protein-Coupled Estrogen Receptor (GPER) in Inflammatory Myopathies.
Neurol Int. 2025 Jul 17;17(7):109. doi: 10.3390/neurolint17070109.
3
Neurosteroid Receptor Modulators for Treating Traumatic Brain Injury.
Neurotherapeutics. 2023 Oct;20(6):1603-1615. doi: 10.1007/s13311-023-01428-7. Epub 2023 Aug 31.
5
The G protein-coupled oestrogen receptor GPER in health and disease: an update.
Nat Rev Endocrinol. 2023 Jul;19(7):407-424. doi: 10.1038/s41574-023-00822-7. Epub 2023 May 16.
6
G Protein-Coupled Estrogen Receptor GPER: Molecular Pharmacology and Therapeutic Applications.
Annu Rev Pharmacol Toxicol. 2023 Jan 20;63:295-320. doi: 10.1146/annurev-pharmtox-031122-121944.
7
Targeting the non-classical estrogen pathway in neurodegenerative diseases and brain injury disorders.
Front Endocrinol (Lausanne). 2022 Sep 15;13:999236. doi: 10.3389/fendo.2022.999236. eCollection 2022.
9
Nuclear Receptors in Myocardial and Cerebral Ischemia-Mechanisms of Action and Therapeutic Strategies.
Int J Mol Sci. 2021 Nov 15;22(22):12326. doi: 10.3390/ijms222212326.
10
17β-Estradiol Abrogates Oxidative Stress and Neuroinflammation after Cortical Stab Wound Injury.
Antioxidants (Basel). 2021 Oct 25;10(11):1682. doi: 10.3390/antiox10111682.

本文引用的文献

1
Recombinant T cell receptor ligand treats experimental stroke.
Stroke. 2009 Jul;40(7):2539-45. doi: 10.1161/STROKEAHA.108.543991. Epub 2009 May 14.
2
The spectrum of systemic immune alterations after murine focal ischemia: immunodepression versus immunomodulation.
Stroke. 2009 Aug;40(8):2849-58. doi: 10.1161/STROKEAHA.109.549618. Epub 2009 May 14.
3
Sex, sex steroids, and brain injury.
Semin Reprod Med. 2009 May;27(3):229-39. doi: 10.1055/s-0029-1216276. Epub 2009 Apr 28.
4
Blockade of adrenoreceptors inhibits the splenic response to stroke.
Exp Neurol. 2009 Jul;218(1):47-55. doi: 10.1016/j.expneurol.2009.03.044. Epub 2009 Apr 14.
6
Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke.
Nat Med. 2009 Feb;15(2):192-9. doi: 10.1038/nm.1927. Epub 2009 Jan 25.
7
Gender and the injured brain.
Anesth Analg. 2008 Jul;107(1):201-14. doi: 10.1213/ane.0b013e31817326a5.
8
Effect of experimental stroke on peripheral immunity: CNS ischemia induces profound immunosuppression.
Neuroscience. 2009 Feb 6;158(3):1098-111. doi: 10.1016/j.neuroscience.2008.05.033. Epub 2008 Jul 1.
9
Estrogen anti-inflammatory activity in brain: a therapeutic opportunity for menopause and neurodegenerative diseases.
Front Neuroendocrinol. 2008 Oct;29(4):507-19. doi: 10.1016/j.yfrne.2008.04.001. Epub 2008 Apr 29.
10
The spleen contributes to stroke-induced neurodegeneration.
J Neurosci Res. 2008 Aug 1;86(10):2227-34. doi: 10.1002/jnr.21661.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验