Radiation-Induced Cognitive Dysfunction After Different Schemes of Fractionated Whole Brain Irradiation

Radiation-induced cognitive dysfunction is a serious complication of radiation therapy. In humans, numerous cases of radiation damage have been recorded after irradiation for therapeutic purposes. The degree of cognitive dysfunctions and its dependence on biological effective doses should be tested in animal preclinical models to minimize radiation side effects. Fractionated whole brain irradiation was performed according to the following schemes: 18 Fractions of 2 Gy each (36Gy/18), 9 fractions of 4 Gy each (36Gy/9), 6 fractions of 6 Gy each (36Gy/6), with the biological effective dose 36Gy, 50.4Gy, 64.8Gy correspondingly. Cognitive impairment was detected by a Novel object recognition test in 36Gy/18 and 36Gy/9 groups. Recognition memory impairment was increased in inverse proportion to the biological effective dose. In the 36Gy/6 group, increased anxiety and decreased research activity in Spontaneous alternation test in Y-shaped maze were observed. Reactions of astroglia and vascular reactions were evaluated using qPCR of Glial Fibrillar Acid Protein (GFAP) and Vascular Endothelial Growth Factor (VEGF) genes and immunohistochemical analyses of these proteins. Despite of various biological effective doses (and its subsequent increasing in chosen 3 fractionation schemes) a dose-depended effect in the expression of VEGF in the prefrontal cortex and GFAP in hippocampus and in cognitive impairment was not observed. Cognitive impairment after fractionated whole brain irradiation was clearly seen in our research. The described pathologic changes in healthy brain play an important role in development of radiation-induced cognitive dysfunction. Therefore, applicability of radiobiological models for evaluation of effects of fractionated whole brain irradiation on cognitive dysfunction put in question in our study. So we can suggest that it needs essential more researches about the choice an optimal fractionated scheme to minimize side effects of ionizing radiation.