Protective Effect of Memantine Hydrochloride on Radiation-induced Cognitive Impairment and Its Mechanism

Ionizing radiation impairs cognition; safe mitigators are needed. Memantine shows clinical benefit during brain irradiation, but mechanisms are unclear.

A mouse model of total-body irradiation injury was established via gamma rays with the establishment of control groups, irradiation groups, and irradiation+memantine groups. Bioinformatic analyses (target prediction, GO/KEGG enrichment, PPI hub identification) and molecular docking were used to nominate candidate targets and pathways for memantine's radioprotection. Guided by these results, hippocampal levels of nitric oxide (NO), peroxynitrite (ONOO - ), inducible nitric oxide synthase (iNOS), and β-amyloid (Aβ42) were quantified.

Memantine improved behavioral performance post-irradiation. Enrichment highlighted neuroactive ligand-receptor interaction and calcium signaling; docking prioritized CYP2D6 and DRD2. In hippocampus, memantine reduced radiation-induced increases in NO, ONOO - , iNOS, and Aβ42.

Memantine hydrochloride attenuates acute radiation-related cognitive deficits, potentially via modulation of synaptic signaling and suppression of nitrosative stress and Aβ42 accumulation. Findings will be interpreted as generating hypotheses that motivate subsequent mechanistic experiments and preliminary translational work.