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Proposal

Pediatric brain cancer patients are at a high risk for radiation-induced cognitive impairment due to white matter changes in the brain. Half of six-month radiotherapy survivors develop significant changes in white matter. Previous research has shown that a mouse model can be used to show similar cognitive and behavioral deficits in human patients. The purpose of this work is to evaluate the effectiveness of two drug therapies, Donepezil and 3,3-Diindolylmethane (DIM), that could be used to either protect the brain from radiation injury or cure the cognitive injury and behavioral deficits that result from whole-brain irradiation. This project consisted of two parts: administration of Donepezil postradiation as a symptomatic cure and administration of DIM before radiation as a protectant. The mice received 30 gray whole brain radiation, and their behavioral changes were measured at 4 and 8 weeks postradiation. Behavioral changes were observed using two tests: the Open Field Test and Marble Burying Test. These tests were to see if the treated mice would have results closer to the healthy baselines established in previous research. From our data, we observed Donepezil to be an ineffective form of therapy, as the deficits did not improve. However, DIM has shown to be a promising protectant drug therapy, as the behavioral data is closer to the results of a healthy control. This research validates the potential of DIM to be used as a radio protectant in preventing both radiation injury and any cognitive deficits from following.

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