Single-cell and Spatial Transcriptomics Reveal Radiation-Induced Disruption of the Blood-Cerebrospinal Fluid Barrier (PRJCA040939)

Radiotherapy is an effective treatment for brain tumors but often leads to radiation-induced brain injury (RIBI) and even irreversible cognitive impairments. However, the pathophysiology underlying RIBI remains elusive, which hinders the development of effective therapies to mitigate its long-term consequences . Here, we employed unbiased single-cell RNA sequencing and spatial transcriptomics techniques to intricately characterize the acute, early delayed, and late phases of RIBI. Our findings shed light on the critical role of the blood-cerebrospinal fluid barrier (BCSFB) in RIBI progression. Increased permeability of the BCSFB facilitates the infiltration of immune cells into the brain parenchyma during the early delayed phase of RIBI. This infiltration initiates dynamic interactions with interferon-responsive microglia, triggering a cascade of inflammatory responses. Additionally, we identified a subtype of choroid plexus epithelial cells potentially involved in maintaining the integrity of the BCSFB.