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

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.