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Ependymal cell inflammatory activation in response to intracerebral hemorrhage.

Overview

Authors: Jing Liu1, Haopu Lin2,3, Xuefeng He4, Yonghe Zheng2,3, Jianan Wu2,3, Qizhen He2,3, Cheng Zhang2,3, Huaping Huang2,3, Xian Yu2,3, Yinan Zhou2,3, Zihang Chen2,3, Hang Zhou2,3, Linfeng Fan2,3, Xiongjie Fu2,3, Tianchi Tang2,3, Guannan Guan2,3, Xiaobo Yu2,3, Xiuqin Feng1, Yushen Du4, Huaijun Chen2,3, Jingyin Chen2,3
  1. Department of Nursing, the Second Affiliated Hospital, School of Medicine, Zhejiang University,Jiefang Road 88th, Hangzhou, Zhejiang 310009 China
  2. Department of Neurosurgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University,Jiefang Road 88th, Hangzhou, Zhejiang 310009 China
  3. Zhejiang Key Laboratory of Research and Transformation for Major Neurosurgical Diseases, Jiefang Road 88th, Hangzhou, Zhejiang 310009 China
  4. Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, School of Medicine, Zhejiang University,Jiefang Road 88th, Hangzhou, Zhejiang 310009 China
Institutions: Zhejiang University (China)
Journal: Journal of neuroinflammation, volume 23, issue 1, article 162
Dates: received 7 January 2026; accepted 6 April 2026; published online 14 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1186/s12974-026-03809-z · PMID 41975484 · PMCID PMC13200338 · OpenAlex W7154174748
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), mouse (organism), stroke (population), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions, Connectivity, fMRI & imaging
Keywords: Intracerebral hemorrhage, Ependymal cell, Complement pathway, Immune activation, Cilia-related function
MeSH: Cerebral Hemorrhage*, Ependyma*, Neuroinflammatory Diseases*, Animals, Inflammation, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic (* major topic)
Topic: Intracerebral and Subarachnoid Hemorrhage Research (Neurology, Medicine), according to OpenAlex
Funding: Postdoctoral Fellowship Program (Grade c) and China Postdoctoral Science Foundation (GZC20251336); National Natural Science Foundation of China (82401724, 82501751, 82301652, 82501543, 82201617, 82271398); Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0505000)
Citations: not cited yet (Europe PMC); 49 references in the paper

Abstract

Background: Neuroinflammation is a central pathological process in secondary brain injury following intracerebral hemorrhage (ICH). While inflammatory responses in perihematomal brain tissue have been extensively investigated, the contribution of ependymal cells to post-ICH neuroinflammatory responses and ventricular pathology remains poorly defined.

Methods: An autologous blood-induced ICH mouse model was used in combination with single-cell RNA sequencing and spatial transcriptomic analyses to characterize transcriptional reprogramming of ependymal cells. EGFP transgenic mice were used to trace the infiltration of peripheral immune cells. Clinical data was used to assess the association between C3 and hematoma volume. Complement pathway activation was evaluated through integrated single-cell transcriptomic analysis, spatial transcriptomic analysis, immunofluorescence staining, and western blot. Bst2-deficient mice were employed to investigate the mechanisms how complement pathway is regulated in ependymal cells.

Results: Single-cell and spatial transcriptomic analysis showed impaired ciliary function and reduced capacity for homeostatic maintenance in ependymal cells. Ventricular asymmetry showed positive association with cognitive impairment at 14-days post-ICH. In parallel, ependymal cells underwent transcriptional reprogramming toward immune and inflammatory phenotypes, accompanied by ipsilateral immune cell infiltration. Cell-cell communication analysis further indicated extensive bidirectional signaling between ependymal cells and multiple immune cell populations, particularly through the complement pathway. Consistent with these findings, elevated C3 expression was detected in ipsilateral ependymal cells. Clinically, circulating C3 levels were elevated in patients with basal ganglia hemorrhage and positively correlated with hematoma volume. Knock out of Bst2 downregulated C3 expression in ependymal cells.

Conclusion: Following ICH, ependymal cells undergo a functional transition characterized by loss of cilia-dependent functions and gain of immune and inflammatory properties, including activation of the complement pathway, particularly C3, regulated by BST2.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12974-026-03809-z.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

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Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 21 authors, 5 keywords, 9 MeSH terms, 3 funders, 49 references.

Cite

This paper

Liu, J., Lin, H., He, X., Zheng, Y., Wu, J., He, Q., Zhang, C., Huang, H., Yu, X., Zhou, Y., Chen, Z., Zhou, H., Fan, L., Fu, X., Tang, T., Guan, G., Yu, X., Feng, X., Du, Y., . . . Chen, J. (2026). Ependymal cell inflammatory activation in response to intracerebral hemorrhage. Journal of neuroinflammation, 23(1), 162. https://doi.org/10.1186/s12974-026-03809-z

BibTeX

@article{liu2026ependymal,
author = {Liu, Jing and Lin, Haopu and He, Xuefeng and Zheng, Yonghe and Wu, Jianan and He, Qizhen and Zhang, Cheng and Huang, Huaping and Yu, Xian and Zhou, Yinan and Chen, Zihang and Zhou, Hang and Fan, Linfeng and Fu, Xiongjie and Tang, Tianchi and Guan, Guannan and Yu, Xiaobo and Feng, Xiuqin and Du, Yushen and Chen, Huaijun and Chen, Jingyin},
title = {{Ependymal cell inflammatory activation in response to intracerebral hemorrhage}},
journal = {Journal of neuroinflammation},
year = {2026},
month = apr,
volume = {23},
number = {1},
pages = {162},
publisher = {BMC},
issn = {1742-2094},
doi = {10.1186/s12974-026-03809-z},
url = {https://doi.org/10.1186/s12974-026-03809-z},
pmid = {41975484},
pmcid = {PMC13200338}
}

RIS

TY - JOUR
AU - Liu, Jing
AU - Lin, Haopu
AU - He, Xuefeng
AU - Zheng, Yonghe
AU - Wu, Jianan
AU - He, Qizhen
AU - Zhang, Cheng
AU - Huang, Huaping
AU - Yu, Xian
AU - Zhou, Yinan
AU - Chen, Zihang
AU - Zhou, Hang
AU - Fan, Linfeng
AU - Fu, Xiongjie
AU - Tang, Tianchi
AU - Guan, Guannan
AU - Yu, Xiaobo
AU - Feng, Xiuqin
AU - Du, Yushen
AU - Chen, Huaijun
AU - Chen, Jingyin
TI - Ependymal cell inflammatory activation in response to intracerebral hemorrhage
T2 - Journal of neuroinflammation
J2 - J Neuroinflammation
PY - 2026
DA - 2026/04/14
VL - 23
IS - 1
SP - 162
SN - 1742-2094
PB - BMC
DO - 10.1186/s12974-026-03809-z
UR - https://doi.org/10.1186/s12974-026-03809-z
LA - en
ER -

CSL-JSON

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