Intravenous administration of mesenchymal stem cell-derived exosomes mitigates traumatic brain injury by inhibiting neutrophil extracellular trap formation via miR-26a-5p.

IF 1.6 4区医学 Q4 NEUROSCIENCES

Neuroreport Pub Date : 2025-06-17 DOI:10.1097/WNR.0000000000002187

Yichao Ye, Xiaoxiang Hou, Xianzheng Sang, Hantong Shi, Yangu Guo, Chengzi Yang, Wen Chen, Hanzi Cai, Chaogui Peng, Yunqing Li, Shi Yu, Danfeng Zhang, Lijun Hou

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引用次数: 0

Abstract

Objective: Traumatic brain injury (TBI) results in severe long-term sequelae. While mesenchymal stem cell-derived exosomes (MSC-Exos) have demonstrated the ability to regulate microglial responses and neuroinflammation, their impact on neutrophil inactivation, particularly in relation to neutrophil extracellular traps (NETs), has not yet been fully elucidated. This research was designed to explore the potential involvement of MSC-Exos in modulating NET formation and microglial polarization following TBI.

Methods: A murine TBI model and an in-vitro lipopolysaccharide-induced microglial activation model were utilized to evaluate the effects of miR-26a-5p-enriched exosomes on NET inhibition, microglial polarization, reduction of neuroinflammation, and promotion of neural function recovery.

Results: Treatment with MSC-Exos post-TBI reduced NET formation and decreased microglial polarization into a proinflammatory phenotype. Genome-wide prediction detected miR-26a-5p as a predominant component of MSC-Exos, which was closely associated with TAB2. Functional assays demonstrated that miR-26a-5p suppressed NET formation in neutrophils and modulated microglial polarization. MRI and histopathological assessments confirmed that MSC-Exos enriched with miR-26a-5p significantly reduced neuronal death and lesion volume. Moreover, miR-26a-5p was found to regulate microglial polarization and reduce neuroinflammation via the TAB2/JNK/AP1 signaling pathway. Cognitive assessments employing the Morris Water Maze and Modified Neurological Severity Scores revealed significant improvements in neural function following treatment.

Conclusion: These findings underscore the potential of MSC-Exos-miR-26a-5p to inhibit NET formation, modulate microglial polarization toward an anti-inflammatory phenotype, and enhance recovery from neural damage in TBI through the TAB2/JNK/AP1 pathway.

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静脉给药间充质干细胞来源的外泌体通过miR-26a-5p抑制中性粒细胞胞外陷阱的形成，从而减轻创伤性脑损伤。

目的：外伤性脑损伤（TBI）具有严重的长期后遗症。虽然间充质干细胞衍生的外泌体（MSC-Exos）已经证明了调节小胶质细胞反应和神经炎症的能力，但它们对中性粒细胞失活的影响，特别是与中性粒细胞胞外陷阱（NETs）有关的影响，尚未完全阐明。本研究旨在探讨mscs - exos在脑外伤后调节NET形成和小胶质细胞极化中的潜在作用。方法：采用小鼠TBI模型和体外脂多糖诱导的小胶质细胞活化模型，评价富集mir -26a-5p外泌体对NET抑制、小胶质细胞极化、减少神经炎症和促进神经功能恢复的影响。结果：在tbi后使用MSC-Exos治疗可减少NET的形成，并减少小胶质细胞极化，形成促炎表型。全基因组预测检测到miR-26a-5p是MSC-Exos的主要成分，与TAB2密切相关。功能分析表明，miR-26a-5p抑制中性粒细胞中NET的形成并调节小胶质细胞极化。MRI和组织病理学评估证实，富含miR-26a-5p的MSC-Exos显著减少神经元死亡和病变体积。此外，miR-26a-5p被发现通过TAB2/JNK/AP1信号通路调节小胶质细胞极化并减少神经炎症。采用莫里斯水迷宫和改良神经严重程度评分的认知评估显示，治疗后神经功能有显著改善。结论：这些发现强调了MSC-Exos-miR-26a-5p抑制NET形成、调节小胶质细胞极化向抗炎表型的潜力，并通过TAB2/JNK/AP1途径促进TBI神经损伤的恢复。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroreport 医学-神经科学

CiteScore

3.20

自引率

0.00%

发文量

150

审稿时长

1 months

期刊介绍： NeuroReport is a channel for rapid communication of new findings in neuroscience. It is a forum for the publication of short but complete reports of important studies that require very fast publication. Papers are accepted on the basis of the novelty of their finding, on their significance for neuroscience and on a clear need for rapid publication. Preliminary communications are not suitable for the Journal. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool. The core interest of the Journal is on studies that cast light on how the brain (and the whole of the nervous system) works. We aim to give authors a decision on their submission within 2-5 weeks, and all accepted articles appear in the next issue to press.