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Microglia‑mediated neuroinflammation in intracerebral hemorrhage: Pathological mechanisms and implications for therapeutic development (Review)

  • Authors:
    • Xuehui Fan
    • Changzhi Pu
    • Luyi Zhong
    • Oucheng Wang
    • Binyi Zhao
    • Dongyi Liao
    • Xue Bai
    • Guiquan Chen
    • Guoqiang Yang
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Manufacturing Laboratory, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Department of Magnetic Resonance Imaging, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Cardiology, Angiology, Haemostaseology, and Medical Intensive Care, Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Heidelberg, Germany, Department of Neurology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Acupuncture and Rehabilitation Department, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
    Copyright: © Fan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 95
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    Published online on: February 16, 2026
       https://doi.org/10.3892/ijmm.2026.5766
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Abstract

Intracerebral hemorrhage (ICH), a life‑threatening subtype of stroke accounting for 10‑15% of global stroke cases, is characterized by high disability and mortality rates, imposing a heavy socioeconomic burden worldwide. Despite its clinical importance, no effective therapeutic interventions exist for this condition. As the resident immune cells of the central nervous system, microglia play a pivotal role in the pathophysiology of ICH. These cells can be activated to adopt either anti‑inflammatory or pro‑inflammatory phenotypes. Following ICH, pro‑inflammatory mediators derived from microglia act as key drivers of neuroinflammation, thereby exacerbating secondary brain injury. By contrast, promoting the phenotypic shift of microglia toward an anti‑inflammatory state has been shown to mitigate an inflammatory response and facilitate neurological recovery. In the present study, existing evidence was reviewed to propose that post‑ICH brain injury and repair are orchestrated not by isolated cells, but by a highly dynamic neuroimmune network centered on microglia. Elucidating the spatiotemporal dynamics and key communicative nodes within this network represents a critical frontier. Moving beyond the classical M1/M2 dichotomy to target this network contextually offers a promising and precise therapeutic aim for future investigations.
View Figures

Figure 1

Polarization of activated microglia
following ICH. After ICH onset, PBI and SBI occur sequentially. PBI
begins with vessel occlusion, followed by rupture, erythrocytes
extravasation and dynamic hematoma expansion, immediately
compressing and damaging adjacent brain tissue, disrupting
surrounding structures and causing early neurological dysfunction.
SBI, emerging hours to days later, is driven by hemolytic products
(such as ferrous ions, hemoglobin and heme), inducing oxidative
stress, inflammation, excitotoxicity and death signals in neurons
and glia. Microglial polarization in response to erythrocyte
lysates post-ICH has three main types: (i) M1 phenotype, which
elevates pro-inflammatory factors and promotes brain damage; (ii)
M2 phenotype, primarily exerting neuroprotection; and (iii) DAM,
identified via single-cell RNA sequencing and other omics, which
can exhibit both neuroprotective and destructive phenotypes,
requiring further investigation. ICH, intracerebral hemorrhage;
PBI, primary brain injury; SBI, secondary brain injury; DAM,
disease-associated microglia; BBB, blood-brain barrier.

Figure 2

Mechanisms underlying activated
microglia-mediated neuroinflammation. The mechanisms associated
with intracerebral hemorrhage following microglial activation
involve various signaling pathways, whose activation can exacerbate
neuroinflammation.

Figure 3

Summary of therapeutic targets and
strategies for microglial polarization after intracerebral
hemorrhage. Various interventions are available to suppress
microglia-mediated neuroinflammation. These targets encompass
signaling pathway proteins, individual proteins, genes and miRNAs.
By modulating these targets, the pro-inflammatory microglial
phenotype can be shifted toward the M2 phenotype. miR or miRNA,
microRNA.
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Copy and paste a formatted citation
Spandidos Publications style
Fan X, Pu C, Zhong L, Wang O, Zhao B, Liao D, Bai X, Chen G and Yang G: Microglia‑mediated neuroinflammation in intracerebral hemorrhage: Pathological mechanisms and implications for therapeutic development (Review). Int J Mol Med 57: 95, 2026.
APA
Fan, X., Pu, C., Zhong, L., Wang, O., Zhao, B., Liao, D. ... Yang, G. (2026). Microglia‑mediated neuroinflammation in intracerebral hemorrhage: Pathological mechanisms and implications for therapeutic development (Review). International Journal of Molecular Medicine, 57, 95. https://doi.org/10.3892/ijmm.2026.5766
MLA
Fan, X., Pu, C., Zhong, L., Wang, O., Zhao, B., Liao, D., Bai, X., Chen, G., Yang, G."Microglia‑mediated neuroinflammation in intracerebral hemorrhage: Pathological mechanisms and implications for therapeutic development (Review)". International Journal of Molecular Medicine 57.4 (2026): 95.
Chicago
Fan, X., Pu, C., Zhong, L., Wang, O., Zhao, B., Liao, D., Bai, X., Chen, G., Yang, G."Microglia‑mediated neuroinflammation in intracerebral hemorrhage: Pathological mechanisms and implications for therapeutic development (Review)". International Journal of Molecular Medicine 57, no. 4 (2026): 95. https://doi.org/10.3892/ijmm.2026.5766
Copy and paste a formatted citation
x
Spandidos Publications style
Fan X, Pu C, Zhong L, Wang O, Zhao B, Liao D, Bai X, Chen G and Yang G: Microglia‑mediated neuroinflammation in intracerebral hemorrhage: Pathological mechanisms and implications for therapeutic development (Review). Int J Mol Med 57: 95, 2026.
APA
Fan, X., Pu, C., Zhong, L., Wang, O., Zhao, B., Liao, D. ... Yang, G. (2026). Microglia‑mediated neuroinflammation in intracerebral hemorrhage: Pathological mechanisms and implications for therapeutic development (Review). International Journal of Molecular Medicine, 57, 95. https://doi.org/10.3892/ijmm.2026.5766
MLA
Fan, X., Pu, C., Zhong, L., Wang, O., Zhao, B., Liao, D., Bai, X., Chen, G., Yang, G."Microglia‑mediated neuroinflammation in intracerebral hemorrhage: Pathological mechanisms and implications for therapeutic development (Review)". International Journal of Molecular Medicine 57.4 (2026): 95.
Chicago
Fan, X., Pu, C., Zhong, L., Wang, O., Zhao, B., Liao, D., Bai, X., Chen, G., Yang, G."Microglia‑mediated neuroinflammation in intracerebral hemorrhage: Pathological mechanisms and implications for therapeutic development (Review)". International Journal of Molecular Medicine 57, no. 4 (2026): 95. https://doi.org/10.3892/ijmm.2026.5766
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