Fractionated radiation-induced acute encephalopathy in a young rat model: cognitive dysfunction and histologic...

Radiation-induced cognitive dysfunction is a common and serious complication after radiation therapy of brain tumor, yet knowledge of its mechanism is poorly understood. The aim of this study was to establish a young rat model for acute radiation encephalopathy, at both cognitive and pathologic levels, induced by fractionated irradiation.

Four-week-old male rats were randomized into sham (0 Gy) and 2 experimental groups receiving fractionated irradiation of 5 Gy/day, 5 days/week, with total doses of 20 and 40 Gy, respectively. Cognition, BBB integrity, and potential astrogliosis were evaluated at 0, 4, 8, and 12 weeks' postirradiation.

Twenty-Gy irradiation led to transient cognitive impairment only at 4 weeks' postirradiation. Forty-Gy irradiation induced cognitive impairment at both 4 and 8 weeks' postirradiation, which was more severe than that induced by 20 Gy. Cognitive impairment was accompanied by a transient increase in BWC only at 4 weeks for the 40-Gy group. Disrupted BBB permeability was detected at 4 and 8 weeks' postirradiation for the 20-Gy group, and at 4, 8, and 12 weeks' postirradiation for 40-Gy group, respectively. Increased astrogliosis in the hippocampus could be detected at 4 weeks' postirradiation for 40-Gy group.

Fractionated irradiation in this experiment could induce acute brain injury, leading to cognitive impairment in young rats. BBB disruption might be a sensitive index for acute radiation encephalopathy. In addition, reactive astrogliosis might play an important role in this process. The present model, especially the 40-Gy irradiation group, is useful for basic and therapeutic studies of acute radiation encephalopathy.