Long-term outcome of changes in cognitive function of young rats after various/different doses of whole brain irradiation

Abstract

Objective: To characterize the early delayed and late-delayed cognitive dysfunction induced by various doses of whole brain irradiation in young rats.Methods: One-month-old Sprague-Dawley male rats were divided randomly into the 0 (control), 0 (anesthesia control), 2, 10, 20, and 30-Gy groups. Each group was then subdivided into 4 groups according to the experimental intervals: 1, 2, 3, and 6 months after radiation. Rats were irradiated using a 4-MeV electron beam, which was generated by a linear accelerator. Sequential behavioral tests, including open field, novel location and novel object recognition and Morris water maze were performed after radiation. Changes in gross neurological symptoms, body weight, topical skin response, and histopathology were observed.Results: In the open field test, there were no radiation-induced alterations found. In the novel location and novel object recognition tests, rats of the 20-Gy group spent less time exploring the novel object and novel location 3 months after irradiation. During the place navigation test, the spatial working memory of the 30 and 20-Gy irradiated rats were impaired from 1 to 2 months after irradiation, respectively. In the spatial probe test, the 20 and 30-Gy irradiated rats spent less time in the critical region compared to control rats at 3 and 6 months post-irradiation. Morphological changes, including edema, vascular dilation, focal necrosis, demyelination, and adjacent reactive gliosis were observed in the 30-Gy irradiation group.Conclusion: More than 20 Gy of whole brain irradiation dose can cause significant cognitive dysfunction in young rats.