The Effects of Exercise on Neurocognitive Impairments in a Translational Model of Pediatric Radiotherapy

Cranial radiation therapy (CRT) is used as a treatment for brain malignancies that are not easily accessible and would provide significant risk to the patient through invasive methods like surgery. While CRT has been shown to be effective as a treatment, healthy areas surrounding the irradiation sites are detrimentally affected. Frontal lobe functions are impaired, particularly the domains of attention, processing speed and inhibition control. These deficits often manifest months to years after radiation and significantly impair quality-of-life over time. Exercise is proposed as an adjuvant therapy to ameliorate the deleterious effects of radiation. We established a rodent model of the neurocognitive effects of CRT. Adolescent Fischer rats were irradiated with a fractionated dose of 20Gy (4Gy x 5 days). We showed lasting neurocognitive impairments in the 5-Choice Serial Reaction Time Task (5-CSRTT), a test that simultaneously measures several cognitive modalities. We investigated whether voluntary exercise could ameliorate these impairments by having physical activity groups exercise from the week after irradiation until behavioral training. We found that exercise significantly ameliorated performance at both 3 months and 6 months post-RT in accuracy, premature responses, and latency to correct responses, along with the number of trials taken to complete stages during training. Our data suggests that exercise significantly mitigates neurocognitive deficits sustained by cranial radiation therapy in our translational model of pediatric radiotherapy.