An Experimental Study of Acute Radiation-Induced Cognitive Dysfunction in a Young Rat Model

Abstract

Radiation-induced cognitive dysfunction is a common and serious clinical complication after radiation therapy for a brain tumor, but the knowledge of its mechanism is poorly understood. The purpose of this study was to establish a young rat model for acute radiation-induced cognitive dysfunction and associated BBB damage, as well as histopathologic changes. Young male rats were randomized into 4 groups to receive irradiation treatments at 300 cGy/min with doses of 0 (sham), 10, 20, and 40 Gy, respectively. Each treatment group was further randomized into 4 subgroups for following up cognitive tests and assessment of their BBB integrity and potential histopathologic changes at 0, 7, 20, and 60 days. We found that irradiation at 10 Gy failed to induce any significant effects. Irradiation at 20 Gy resulted in a transient impairment of the cognitive functions at 7 and 20 days and returned to normal at 60 days. Irradiation at 40 Gy caused the severest cognitive impairment, which peaked at 7 days, and lasted for at least 60 days. The impaired cognition in both the 20-Gy and 40-Gy-irradiated rats was more or less accompanied with increased brain water content and deteriorated BBB function, though mild histopathologic alternations were only noticed in the 40-Gy-irradiated rats at 20 days. A single-dose exposure at 20 to 40 Gy is sufficient to induce acute brain injury at both cognitive and pathologic levels in young male rats. In addition, morphologic outcomes may not be sensitive enough to reveal all of the pathologic changes, whereas BBB disruption may be an earlier and more sensitive index for acute RE. Therefore, the present model is useful for basic and therapeutic studies of acute RE.