Blocking of Tim-3 Ameliorates Spinal Cord Ischemia-Reperfusion Injury Through Inhibiting Neuroinflammation and Promoting M1-to-M2 Phenotypic Polarization of Microglia

IF 3.1 4区 医学 Q3 IMMUNOLOGY Immunity, Inflammation and Disease Pub Date : 2024-12-06 DOI:10.1002/iid3.70084
Zhenxing Li, Binbin Zhou, Guanghui Chen, Xiangyu Yang, Han Su, Bolin Li
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Abstract

Background

Blocking of Tim-3 exerts therapeutic effects in a series of ischemia-reperfusion injury (IRI).

Methods

In this work, a cross-clamped aortic arch was conducted to establish SCIRI rat model. Besides, rat spinal microglia was subjected to OGD/R to mimic I/R-like conditions in vitro. The in vivo and in vitro therapeutic effects of Tim-3 antibody in SCIRI were investigated from these aspects: neuronal apoptosis, neuroinflammation, microglia activation, and polarization.

Results

It was verified that Tim-3 was highly expressed in spinal cord tissues of SCIRI rats and blocking of Tim-3 attenuated SCIRI-induced pathological injury, neuronal apoptosis, neuroinflammation, and microglia activation (M1 polarization). In addition, it was verified that Tim-3 was highly expressed in OGD/R-treated rat spinal microglia and blocking of Tim-3 attenuated OGD/R-induced inflammation and spinal microglia activation (M1 polarization).

Conclusions

Tim-3 antibody can exert therapeutic effects in SCIRI through inhibiting neuroinflammation and promoting microglia polarization from M1 to M2 phenotype.

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阻断Tim-3通过抑制神经炎症和促进小胶质细胞M1-to-M2表型极化改善脊髓缺血再灌注损伤
背景:阻断Tim-3在一系列缺血再灌注损伤(IRI)中发挥治疗作用。方法:采用交叉夹紧主动脉弓建立SCIRI大鼠模型。此外,在体外对大鼠脊髓小胶质细胞进行OGD/R模拟I/R样条件。从神经元凋亡、神经炎症、小胶质细胞活化、极化等方面研究Tim-3抗体对SCIRI的体内外治疗作用。结果:证实Tim-3在scii大鼠脊髓组织中高表达,阻断Tim-3可减轻scii诱导的病理性损伤、神经元凋亡、神经炎症和小胶质细胞激活(M1极化)。此外,证实Tim-3在OGD/ r处理大鼠脊髓小胶质细胞中高表达,阻断Tim-3可减轻OGD/ r诱导的炎症和脊髓小胶质细胞激活(M1极化)。结论:Tim-3抗体可通过抑制神经炎症和促进小胶质细胞从M1向M2表型极化来发挥治疗scii的作用。
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来源期刊
Immunity, Inflammation and Disease
Immunity, Inflammation and Disease Medicine-Immunology and Allergy
CiteScore
3.60
自引率
0.00%
发文量
146
审稿时长
8 weeks
期刊介绍: Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including: • cellular and molecular immunology • clinical immunology • allergy • immunochemistry • immunogenetics • immune signalling • immune development • imaging • mathematical modelling • autoimmunity • transplantation immunology • cancer immunology
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