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. 2025 Jul;173(3):571-582.
doi: 10.1007/s11060-025-05018-9. Epub 2025 Apr 17.

Elucidating the complexity of radiation-induced brain injury: comprehensive assessment of hippocampal and cortical impacts

Beibei Chen  1   2 , Yao Wang  3 , Ruili Dang  2 , ShiYuan Zhao  2 , Shanshan Wei  4 , Jialu Li  5 , Xiangjiao Meng #  6 , Rong Rong #  7 , Pei Jiang #  8   9
Affiliations

Elucidating the complexity of radiation-induced brain injury: comprehensive assessment of hippocampal and cortical impacts

Beibei Chen et al. J Neurooncol. 2025 Jul.

Abstract

Purpose: Radiation-induced brain injury (RIBI) poses significant clinical challenges, underscoring the limited mechanistic understanding in this field. This study systematically investigates both the genetic and metabolic alterations induced by RIBI and their differential regional impacts across brain structures.

Methods: Mice received cranial irradiation with a single 30 Gy X-ray dose. Behavioral assessments, including the open field test (OFT), elevated plus maze test (EPM), and Morris water maze test (MWM), were conducted to evaluate the impact of RIBI on mouse behavior. Hippocampal and cortical tissues were subjected to transcriptomic and metabolomic analyses to identify alterations in gene expression and metabolic profiles.

Results: Behavioral tests indicated that irradiated mice exhibited significant impairments in exploration behavior, anxiety levels, and memory capabilities compared to controls. Transcriptomic analysis identified 456 and 516 significantly altered genes in the hippocampus and cerebral cortex, respectively. Metabolomic analysis identified 253 and 335 significantly altered metabolites in the hippocampus and cerebral cortex, respectively. Integrated pathway analysis uncovered region-specific alterations, while also highlighting shared perturbations in pathways such as glycerophospholipid metabolism, cAMP signaling, and the TCA cycle, suggesting these pathways as key biological processes affected by RIBI.

Conclusions: This study delineates the genetic and metabolic alterations induced by RIBI in the hippocampus and cerebral cortex. Our findings reveal both region-specific and shared characteristics of RIBI, providing a foundation for understanding the differential effects of radiation-induced injury across brain regions.

Keywords: Behavioral assessment; Metabolomics; Radiation-induced brain injury (RIBI); Transcriptomics.

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Conflict of interest statement

Declarations. Ethical approval: The animal study protocol was approved by the Ethics Committee of Shandong First Medical University Affiliated Cancer Hospital (protocol no. SDTHEC2024002013). Competing interests: The authors declare no competing interests.

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