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褪黑素促进短暂性局灶性脑缺血小鼠模型中B细胞成熟并减轻缺血后免疫缺陷。

Melatonin Promotes B-Cell Maturation and Attenuates Post-Ischemic Immunodeficiency in a Murine Model of Transient Focal Cerebral Ischemia.

作者信息

Tai Shih-Huang, Hsu Hao-Hsiang, Huang Sheng-Yang, Chen Yu-Ning, Chen Liang-Yi, Lee Ai-Hua, Lee Ai-Chiang, Lee E-Jian

机构信息

Neurophysiology Laboratory, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan, 70428, Taiwan.

Department of Occupational Safety and Health, Chung Hwa University of Medical Technology, Tainan, Taiwan.

出版信息

J Neuroimmune Pharmacol. 2025 Jun 2;20(1):62. doi: 10.1007/s11481-025-10222-5.

DOI:10.1007/s11481-025-10222-5
PMID:40455093
Abstract

In this study, we investigated the immunomodulatory effects of melatonin on B-cell maturation and its potential to mitigate immunodeficiency following transient focal cerebral ischemia in mice. Transient middle cerebral artery occlusion (MCAO) was induced in adult C57BL/6 mice, followed by melatonin administration. We evaluated the effects of melatonin on neutrophil infiltration, macrophage and microglial activation in the ischemic brain, and B-cell maturation in both the central nervous system and peripheral blood. Melatonin treatment significantly reduced pro-inflammatory cell infiltration in the ischemic hemisphere and promoted B-cell maturation, reflecting robust immunomodulatory activity. These immune changes coincided with improved neurological outcomes and reduced cerebral edema. Collectively, our findings suggest that melatonin may serve as a promising therapeutic candidate in ischemic stroke, addressing both immunodeficiency and neuronal injury.

摘要

在本研究中,我们调查了褪黑素对B细胞成熟的免疫调节作用及其减轻小鼠短暂性局灶性脑缺血后免疫缺陷的潜力。在成年C57BL/6小鼠中诱导短暂性大脑中动脉闭塞(MCAO),随后给予褪黑素。我们评估了褪黑素对缺血性脑内中性粒细胞浸润、巨噬细胞和小胶质细胞活化以及中枢神经系统和外周血中B细胞成熟的影响。褪黑素治疗显著减少了缺血半球的促炎细胞浸润并促进了B细胞成熟,反映出强大的免疫调节活性。这些免疫变化与改善的神经学结果和减轻的脑水肿相一致。总体而言,我们的研究结果表明,褪黑素可能是缺血性中风中有前景的治疗候选药物,可解决免疫缺陷和神经元损伤问题。

相似文献

1
Melatonin Promotes B-Cell Maturation and Attenuates Post-Ischemic Immunodeficiency in a Murine Model of Transient Focal Cerebral Ischemia.褪黑素促进短暂性局灶性脑缺血小鼠模型中B细胞成熟并减轻缺血后免疫缺陷。
J Neuroimmune Pharmacol. 2025 Jun 2;20(1):62. doi: 10.1007/s11481-025-10222-5.
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Administration of melatonin after onset of ischemia reduces the volume of cerebral infarction in a rat middle cerebral artery occlusion stroke model.在大鼠大脑中动脉闭塞性中风模型中,缺血发作后给予褪黑素可减少脑梗死体积。
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Melatonin decreases neurovascular oxidative/nitrosative damage and protects against early increases in the blood-brain barrier permeability after transient focal cerebral ischemia in mice.褪黑素可减少神经血管的氧化/亚硝化损伤,并防止小鼠短暂性局灶性脑缺血后血脑屏障通透性的早期增加。
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Melatonin attenuates the postischemic increase in blood-brain barrier permeability and decreases hemorrhagic transformation of tissue-plasminogen activator therapy following ischemic stroke in mice.褪黑素可减轻小鼠缺血性卒中后血脑屏障通透性的增加,并减少组织型纤溶酶原激活剂治疗后的组织出血性转化。
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Postischemic brain infiltration of leukocyte subpopulations differs among murine permanent and transient focal cerebral ischemia models.缺血后白细胞亚群浸润在小鼠永久性和短暂性局灶性脑缺血模型中存在差异。
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本文引用的文献

1
Updates of the role of B-cells in ischemic stroke.B细胞在缺血性卒中中作用的研究进展
Front Cell Neurosci. 2024 Mar 14;18:1340756. doi: 10.3389/fncel.2024.1340756. eCollection 2024.
2
Melatonin: a promising neuroprotective agent for cerebral ischemia-reperfusion injury.褪黑素:一种用于脑缺血再灌注损伤的有前景的神经保护剂。
Front Aging Neurosci. 2023 Aug 4;15:1227513. doi: 10.3389/fnagi.2023.1227513. eCollection 2023.
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Immunodepression, Infections, and Functional Outcome in Ischemic Stroke.缺血性卒中中的免疫抑制、感染及功能转归
Stroke. 2022 May;53(5):1438-1448. doi: 10.1161/STROKEAHA.122.038867. Epub 2022 Mar 28.
4
Central Nervous System-Infiltrating T Lymphocytes in Stroke Are Activated via Their TCR (T-Cell Receptor) but Lack CD25 Expression.中风中浸润中枢神经系统的T淋巴细胞通过其T细胞受体(TCR)被激活,但缺乏CD25表达。
Stroke. 2021 Aug;52(9):2939-2947. doi: 10.1161/STROKEAHA.120.032763. Epub 2021 Jul 16.
5
Immune responses to stroke: mechanisms, modulation, and therapeutic potential.对中风的免疫反应:机制、调节及治疗潜力。
J Clin Invest. 2020 Jun 1;130(6):2777-2788. doi: 10.1172/JCI135530.
6
Melatonin protects against ischemic stroke by modulating microglia/macrophage polarization toward anti-inflammatory phenotype through STAT3 pathway.褪黑素通过 STAT3 通路调节小胶质细胞/巨噬细胞向抗炎表型极化,从而起到对缺血性中风的保护作用。
CNS Neurosci Ther. 2019 Dec;25(12):1353-1362. doi: 10.1111/cns.13261.
7
Microglial activation after ischaemic stroke.缺血性脑卒中后的小胶质细胞激活。
Stroke Vasc Neurol. 2019 May 10;4(2):71-74. doi: 10.1136/svn-2018-000196. eCollection 2019 Jul.
8
Melatonin as a master regulator of cell death and inflammation: molecular mechanisms and clinical implications for newborn care.褪黑素作为细胞死亡和炎症的主要调节剂:对新生儿护理的分子机制和临床意义。
Cell Death Dis. 2019 Apr 8;10(4):317. doi: 10.1038/s41419-019-1556-7.
9
Role of Immune Cells Migrating to the Ischemic Brain.免疫细胞向缺血性脑迁移的作用。
Stroke. 2018 Sep;49(9):2261-2267. doi: 10.1161/STROKEAHA.118.021474.
10
Melatonin and inflammation-Story of a double-edged blade.褪黑素与炎症——一把双刃剑的故事。
J Pineal Res. 2018 Nov;65(4):e12525. doi: 10.1111/jpi.12525. Epub 2018 Oct 12.