Injury to repair: Functions of microglia and monocyte-derived cells in ischemic stroke

IF 1.8 4区医学 Q3 NEUROSCIENCES

Journal of Stroke & Cerebrovascular Diseases Pub Date : 2025-09-17 DOI:10.1016/j.jstrokecerebrovasdis.2025.108422

Ryan Martynowicz BS , David P. Sullivan PhD , Ayush Batra MD

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引用次数: 0

Abstract

Introduction

Microglia, the central nervous system’s resident immune cells, play a complex role in acute ischemic stroke (AIS), contributing to both neuroprotection and secondary neurologic injury. After ischemic injury, microglia activate and adopt a diverse range of phenotypes, from extremes of pro-inflammatory to anti-inflammatory microglia. Coinciding with microglial activation, AIS triggers infiltration of monocytes, which transform into monocyte-derived cells (MdCs) within the ischemic microenvironment. MdCs display many overlapping characteristics with microglia, complicating their identification and role in recovery.

Methods

This narrative review synthesizes current basic and translational research examining the heterogeneity and interplay of microglia and MdCs in response to AIS. Relevant literature was identified through a comprehensive search of the PubMed database, inclusive of studies published through June 2025.

Results and Conclusions

Anti-inflammatory microglial phenotypes promote neuronal survival, phagocytosis of necrotic debris, and blood-brain barrier repair. Pro-inflammatory microglial phenotypes, conversely, exacerbate injury through excitotoxicity, cytokine release, and vascular disruption. Initially, MdCs adopt a neuroprotective, reparative microglia-like role by phagocytizing debris and supporting repair but later shift to a pro-inflammatory phenotype, driving secondary damage. The dynamic interaction between microglia and MdCs is crucial for stroke recovery, with microglia and MdCs initially aiding in tissue repair and angiogenesis while subsequently amplifying secondary injury through pro-inflammatory phenotypes. Although various biomarkers have been proposed to differentiate microglia from MdCs and predict stroke outcomes, none have been clinically validated. Further studies are needed to identify reliable biomarkers for these distinct cell types and develop strategies to minimize secondary injury without impairing recovery after stroke.

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损伤修复：缺血性中风中小胶质细胞和单核细胞来源细胞的功能。

小胶质细胞是中枢神经系统的常驻免疫细胞，在急性缺血性卒中（AIS）中发挥着复杂的作用，既可以起到神经保护作用，也可以起到继发性神经损伤的作用。缺血损伤后，小胶质细胞激活并采用多种表型，从促炎到抗炎的极端小胶质细胞。与小胶质细胞激活相一致，AIS触发单核细胞浸润，单核细胞在缺血微环境中转化为单核细胞衍生细胞（MdCs）。MdCs显示出许多与小胶质细胞重叠的特征，使它们的识别和在恢复中的作用变得复杂。方法：本文综合了目前的基础和转化研究，探讨了小胶质细胞和MdCs在AIS反应中的异质性和相互作用。通过对PubMed数据库的全面搜索确定了相关文献，包括截至2025年6月发表的研究。结果和结论：抗炎小胶质细胞表型促进神经元存活、坏死碎片吞噬和血脑屏障修复。相反，促炎小胶质细胞表型通过兴奋毒性、细胞因子释放和血管破坏加剧损伤。最初，MdCs通过吞噬碎片和支持修复来发挥神经保护、修复小胶质细胞的作用，但后来转变为促炎表型，导致继发性损伤。小胶质细胞和MdCs之间的动态相互作用对中风恢复至关重要，小胶质细胞和MdCs最初有助于组织修复和血管生成，随后通过促炎表型放大继发性损伤。尽管已经提出了各种生物标志物来区分小胶质细胞和MdCs并预测卒中结局，但没有一个得到临床验证。需要进一步的研究来确定这些不同细胞类型的可靠生物标志物，并制定策略来减少继发性损伤而不损害中风后的恢复。

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

Journal of Stroke & Cerebrovascular Diseases Medicine-Surgery

CiteScore

5.00

自引率

4.00%

发文量

583

审稿时长

62 days

期刊介绍： The Journal of Stroke & Cerebrovascular Diseases publishes original papers on basic and clinical science related to the fields of stroke and cerebrovascular diseases. The Journal also features review articles, controversies, methods and technical notes, selected case reports and other original articles of special nature. Its editorial mission is to focus on prevention and repair of cerebrovascular disease. Clinical papers emphasize medical and surgical aspects of stroke, clinical trials and design, epidemiology, stroke care delivery systems and outcomes, imaging sciences and rehabilitation of stroke. The Journal will be of special interest to specialists involved in caring for patients with cerebrovascular disease, including neurologists, neurosurgeons and cardiologists.