# A novel paradigm for chronic subdural hematoma: regenerative medicine strategies targeting the pathological microenvironment

**Authors:** Zhijian Xu, Song Yang, Guifang Zheng, Huahui Chen, Xing Wan, Hu Xu, Yutiao Xu, Jian Wang, Minfeng Tong, Qi Tu

PMC · DOI: 10.3389/fcell.2026.1757623 · Frontiers in Cell and Developmental Biology · 2026-02-11

## TL;DR

This paper explores new regenerative strategies to treat chronic subdural hematoma by targeting its complex microenvironment.

## Contribution

The paper introduces regenerative medicine approaches to treat chronic subdural hematoma by focusing on its pathological microenvironment.

## Key findings

- Chronic subdural hematoma involves chronic inflammation, abnormal angiogenesis, and ECM imbalance.
- Regenerative strategies like immunomodulation and stem cell therapy target the microenvironment for treatment.
- These approaches aim to restore tissue homeostasis and shift treatment from surgery to biological remodeling.

## Abstract

This review systematically summarizes the pathological microenvironment characteristics of chronic subdural hematoma (CSDH) and the regenerative medicine strategies for its intervention. CSDH is no longer regarded as a simple mechanical hematoma but is recognized as a dynamic pathological process driven by chronic inflammation, abnormal angiogenesis, extracellular matrix (ECM) imbalance, and interactions among immune cells. The article focuses on key cellular and molecular mechanisms within the microenvironment and highlights regulatory strategies targeting inflammation, vascular leakage, and matrix remodeling. These strategies include immunomodulation, stem cell therapy, exosome- and nanomaterial-based delivery systems. Such innovative approaches aim to restore tissue homeostasis at the biological level, advancing CSDH treatment from traditional surgical drainage toward microenvironment remodeling and functional reconstruction. They provide a theoretical basis for achieving precise and regenerative clinical therapies.

## Full-text entities

- **Genes:** SERPINE1 (serpin family E member 1) [NCBI Gene 5054] {aka PAI, PAI-1, PAI1, PLANH1}, MIR146A (microRNA 146a) [NCBI Gene 406938] {aka MIRN146, MIRN146A, miR-146a, miRNA146A}, HMGB1 (high mobility group box 1) [NCBI Gene 3146] {aka HMG-1, HMG1, HMG3, SBP-1}, MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, PLAT (plasminogen activator, tissue type) [NCBI Gene 5327] {aka T-PA, TPA}, ITGB1 (integrin subunit beta 1) [NCBI Gene 3688] {aka CD29, FNRB, GPIIA, MDF2, MSK12, VLA-BETA}, FGF2 (fibroblast growth factor 2) [NCBI Gene 2247] {aka BFGF, FGF-2, FGFB, HBGF-2}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, PXN (paxillin) [NCBI Gene 5829], IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, PTK2 (protein tyrosine kinase 2) [NCBI Gene 5747] {aka FADK, FADK 1, FAK, FAK1, FRNK, PPP1R71}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, CLDN5 (claudin 5) [NCBI Gene 7122] {aka AWAL, BEC1, CPETRL1, TMDVCF, TMVCF}, TEK (TEK receptor tyrosine kinase) [NCBI Gene 7010] {aka CD202B, GLC3E, TIE-2, TIE2, VMCM, VMCM1}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, ANGPT2 (angiopoietin 2) [NCBI Gene 285] {aka AGPT2, ANG2, LMPHM10}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, ANG (angiogenin) [NCBI Gene 283] {aka ALS9, HEL168, RAA1, RNASE4, RNASE5}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, KLF2 (KLF transcription factor 2) [NCBI Gene 10365] {aka LKLF}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, OCLN (occludin) [NCBI Gene 100506658] {aka BLCPMG, PPP1R115, PTORCH1}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}
- **Diseases:** vascular instability (MESH:D043171), CSDH (MESH:D020200), toxicity (MESH:D064420), endothelial injury (MESH:D057772), hemorrhagic (MESH:D006470), subdural haematoma (MESH:D006408), intracranial hemorrhagic disorders (MESH:D020300), neural disorders (MESH:D015441), Hematoma (MESH:D006406), fibrosis (MESH:D005355), chronic inflammation (MESH:D007249)
- **Chemicals:** atorvastatin (MESH:D000069059)
- **Species:** Homo sapiens (human, species) [taxon 9606], HC [taxon 11103]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12932478/full.md

## References

61 references — full list in the complete paper: https://tomesphere.com/paper/PMC12932478/full.md

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Source: https://tomesphere.com/paper/PMC12932478