A spatiotemporal atlas of radiation-induced brain injury reveals dysfunction of the blood-CSF barrier
6 affiliations
- 1Academy of Military Medical Sciences, Beijing 100850, P.R. China
- 2Department of Neurosurgery, the First Medical Center, Chinese PLA General Hospital, Beijing 100853, P.R. China
- 3School of Computer, Electronic and Information, Guangxi University, Nanning, Guangxi Zhuang Autonomous Region 530004, P.R. China
- 4Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China
- 5Medical College of Guizhou University, Guiyang, Guizhou 550025, P.R. China
- 6Collaborative Innovation Center for Personalized Cancer Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
Abstract
Radiotherapy for brain tumors frequently induces irreversible cognitive decline, yet the underlying mechanisms remain poorly understood. Here, we present an integrated single-cell and spatial transcriptomic atlas of radiation-induced brain injury (RIBI) in mice, spanning the acute to chronic phases. We reveal that the early-delayed phase following irradiation represents a critical window during which the blood-cerebrospinal fluid barrier (BCSFB) integrity is compromised. This disruption results from the selective depletion of a radiosensitive Tmsb4x+ epithelial subpopulation in the choroid plexus, which functions as a gatekeeper for the BCSFB. Consequently, CSF-derived macrophages excessively infiltrate the periventricular niche and engage in spatial crosstalk with interferon-responsive microglia. This dysregulated immune axis sustains chronic neuroinflammation, driving the late-stage neurodegeneration and cognitive impairment. In conclusion, our study establishes a high-resolution spatiotemporal framework and positions the BCSFB as a pivotal immune gateway and a promising therapeutic target for mitigating RIBI.
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BibTeX
@article{quan2026spatiotemporal,
title = {{A spatiotemporal atlas of radiation-induced brain injury reveals dysfunction of the blood-CSF barrier}},
author = {Cheng Quan and Yan Gao and Xinyi Liu and Jiabao Xiang and Jiashu Zhang and Liping Chen and Ying Li and Weiming Gao and Kaina Hao and Guohang He and Di Liu and Aogang Wang and Hongyue Tian and Hao Lu and Jie Ping and Siao Jiang and Qilin Huang and Yinglong Wu and Haitao Wu and Yiming Lu and Gangqiao Zhou},
journal = {Cell Reports Medicine},
year = {2026},
month = oct,
doi = {10.1016/j.xcrm.2026.103097},
url = {https://doi.org/10.1016/j.xcrm.2026.103097},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - A spatiotemporal atlas of radiation-induced brain injury reveals dysfunction of the blood-CSF barrier
AU - Cheng Quan
AU - Yan Gao
AU - Xinyi Liu
AU - Jiabao Xiang
AU - Jiashu Zhang
AU - Liping Chen
AU - Ying Li
AU - Weiming Gao
AU - Kaina Hao
AU - Guohang He
AU - Di Liu
AU - Aogang Wang
AU - Hongyue Tian
AU - Hao Lu
AU - Jie Ping
AU - Siao Jiang
AU - Qilin Huang
AU - Yinglong Wu
AU - Haitao Wu
AU - Yiming Lu
AU - Gangqiao Zhou
PY - 2026
DA - 2026/10/08
JO - Cell Reports Medicine
DO - 10.1016/j.xcrm.2026.103097
UR - https://doi.org/10.1016/j.xcrm.2026.103097
AB - Radiotherapy for brain tumors frequently induces irreversible cognitive decline, yet the underlying mechanisms remain poorly understood. Here, we present an integrated single-cell and spatial transcriptomic atlas of radiation-induced brain injury (RIBI) in mice, spanning the acute to chronic phases. We reveal that the early-delayed phase following irradiation represents a critical window during which the blood-cerebrospinal fluid barrier (BCSFB) integrity is compromised. This disruption results from the selective depletion of a radiosensitive Tmsb4x+ epithelial subpopulation in the choroid plexus, which functions as a gatekeeper for the BCSFB. Consequently, CSF-derived macrophages excessively infiltrate the periventricular niche and engage in spatial crosstalk with interferon-responsive microglia. This dysregulated immune axis sustains chronic neuroinflammation, driving the late-stage neurodegeneration and cognitive impairment. In conclusion, our study establishes a high-resolution spatiotemporal framework and positions the BCSFB as a pivotal immune gateway and a promising therapeutic target for mitigating RIBI.
SN - 2666-3791
ER -