Microglial state dynamics in intracerebral hemorrhage: A systems-level integration from molecular networks to precision therapeutics.

Authors

Jun Yan, Shuling Tang, Cameron Lenahan, Weilin Xu, Yong Mo, Hui Li, Jianbin Bi, Qin Hu, Ligen Mo

Published in

Experimental neurology. Pages 116038. Oct 03, 2026. Epub Oct 03, 2026.

Abstract

Intracerebral hemorrhage (ICH) induces secondary brain injury through a dynamic neuroimmune network rather than a single process of microglial "activation." After hemorrhage, resident microglia, infiltrating monocyte-derived macrophages, neutrophils, neurovascular-unit cells, and blood-derived injury signals, including thrombin, hemoglobin, heme, iron, DAMPs, complement, and lipid debris, jointly shape the evolving perihematomal immune microenvironment. The traditional M1/M2 polarization framework has provided historical heuristic value, but it is no longer sufficient as an organizing model for post-ICH myeloid biology. Accordingly, this review uses consensus-aligned terminology, including microglial states, state transitions, functional programs, transcriptional clusters, spatial niches, and myeloid-cell states, while retaining M1/M2 terminology only when discussing historical literature. Evidence from human perihematomal tissue, hematoma samples, rodent ICH models, single-cell and spatial transcriptomics, and mechanistic intervention studies indicates that post-ICH myeloid responses comprise heterogeneous inflammatory, metabolic-stress, lipid-handling, phagocytic-lysosomal, antigen-presentation, proliferative, and repair-associated programs. Here, we propose a systems-level framework defined as a conceptual synthesis and translational therapeutic framework, rather than a validated quantitative systems biology model. This framework integrates microglial state transitions, spatiotemporal mismatch, resident microglia-monocyte-derived macrophage distinction, neurovascular crosstalk, and therapeutic decision points. We further introduce the immunometabolic constraint as a working hypothesis: although inflammation, metabolism, phagocytosis, and hematoma clearance are each metabolically regulated, direct evidence for a quantifiable metabolic competition between inflammatory suppression and phagocytic enhancement in ICH remains lacking. Future studies require lineage-resolved, spatially informed, functionally validated, and biomarker-guided approaches.

PMID:
42829066
Bibliographic data and abstract were imported from PubMed on 04 Oct 2026.

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