Dimethyl Fumarate Modulates the Immune Environment and Improves Prognosis in the Acute Phase after Ischemic Stroke.

IF 2.2 4区医学 Q3 ENDOCRINOLOGY & METABOLISM Neuroimmunomodulation Pub Date : 2024-01-01 Epub Date: 2024-06-06 DOI:10.1159/000539589

Chunrui Bo, Jingkai Li, Junjie Wang, Yaxin Zhang, Tao Wu, Mingyang Wang, Shiyue Hou, Yan Liang, Xiyue Zhang, Shufang Zhao, Huixue Zhang, Jianjian Wang, Lihua Wang, Lianmei Zhong

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Abstract

Introduction: Dimethyl fumarate (DMF) has shown potential for protection in various animal models of neurological diseases. However, the impact of DMF on changes in peripheral immune organs and the central nervous system (CNS) immune cell composition after ischemic stroke remains unclear.

Methods: Eight-week-old C57BL/6J mice with photothrombosis ischemia and patients with acute ischemic stroke (AIS) were treated with DMF. TTC staining, flow cytometry, and immunofluorescence staining were used to evaluate the infarct volume and changes in immune cells in the periphery and the CNS.

Results: DMF reduced the infarct volume on day 1 after PT. DMF reduced the percentages of peripheral immune cells, such as neutrophils, dendritic cells, macrophages, and monocytes, on day 1, followed by NK cells on day 3 and B cells on day 7 after PT. In the CNS, DMF significantly reduced the percentage of monocytes in the brain on day 3 after PT. In addition, DMF increased the number of microglia in the peri-infarct area and reduced the number of neurons in the peri-infarct area in the acute and subacute phases after PT. In AIS patients, B cells decreased in patients receiving alteplase in combination with DMF.

Conclusion: DMF can change the immune environment of the periphery and the CNS, reduce infarct volume in the acute phase, promote the recruitment of microglia and preserve neurons in the peri-infarct area after ischemic stroke.

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富马酸二甲酯能调节免疫环境，改善缺血性中风后急性期的预后。

简介：富马酸二甲酯（DMF）在多种神经系统疾病动物模型中显示出潜在的保护作用。然而，DMF对缺血性脑卒中后外周免疫器官和中枢神经系统（CNS）免疫细胞组成变化的影响仍不清楚：方法：用 DMF 治疗光栓（PT）缺血的八周龄 C57BL/6J 小鼠和急性缺血性脑卒中（AIS）患者。采用TTC染色法、流式细胞术和免疫荧光染色法评估梗死体积以及外周和中枢神经系统免疫细胞的变化：结果：DMF缩小了PT后第1天的梗死体积。DMF在PT后第1天降低了中性粒细胞、树突状细胞、巨噬细胞和单核细胞等外周免疫细胞的百分比，随后在第3天降低了NK细胞的百分比，在第7天降低了B细胞的百分比。在中枢神经系统中，DMF 在 PT 后第 3 天显著降低了脑内单核细胞的百分比。此外，在 PT 后的急性期和亚急性期，DMF 增加了梗死周围区域的小胶质细胞数量，减少了梗死周围区域的神经元数量。在AIS患者中，接受阿替普酶联合DMF治疗的患者B细胞减少：结论：DMF可改变缺血性脑卒中患者外周和中枢神经系统的免疫环境，减少急性期梗死体积，促进小胶质细胞的募集，保护梗死周围神经元。

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来源期刊

Neuroimmunomodulation 医学-免疫学

CiteScore

3.60

自引率

4.20%

发文量

审稿时长

>12 weeks

期刊介绍： The rapidly expanding area of research known as neuroimmunomodulation explores the way in which the nervous system interacts with the immune system via neural, hormonal, and paracrine actions. Encompassing both basic and clinical research, ''Neuroimmunomodulation'' reports on all aspects of these interactions. Basic investigations consider all neural and humoral networks from molecular genetics through cell regulation to integrative systems of the body. The journal also aims to clarify the basic mechanisms involved in the pathogenesis of the CNS pathology in AIDS patients and in various neurodegenerative diseases. Although primarily devoted to research articles, timely reviews are published on a regular basis.