pifithrin-mu and Head-and-Neck-Neoplasms

Cognitive impairment, termed chemobrain, is a common neurotoxicity associated with chemotherapy treatment, affecting an estimated 78% of patients. Prompted by the hypothesis that neuronal mitochondrial dysfunction underlies chemotherapy-induced cognitive impairment (CICI), we explored the efficacy of administering the small-molecule pifithrin (PFT)-μ, an inhibitor of mitochondrial p53 accumulation, in preventing CICI. Male C57BL/6J mice injected with cisplatin ± PFT-μ for two 5-day cycles were assessed for cognitive function using novel object/place recognition and alternation in a Y-maze. Cisplatin impaired performance in the novel object/place recognition and Y-maze tests. PFT-μ treatment prevented CICI and associated cisplatin-induced changes in coherency of myelin basic protein fibers in the cingular cortex and loss of doublecortin

Topics: Animals; Antineoplastic Agents; Blotting, Western; Brain; Cisplatin; Cognition Disorders; Disease Models, Animal; Head and Neck Neoplasms; Male; Maze Learning; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Mitochondria; Neurons; Neuroprotective Agents; Real-Time Polymerase Chain Reaction; Sulfonamides; Tumor Suppressor Protein p53