抄録
The numbers of brain tumors survivors who receive whole-brain irradiation (WBI) develop progressive cognitive dysfunction. WBI-induced decrease in neurogenesis in hippocampus is involved in the delayed cognitive impairment. Considerable data suggests that the continuous suppression of neurogenesis may be due to the activated microglia. To clarify the mechanisms of the radiation-induced deficits in cognitive function, we studied an early response of the hippocampal proliferating cells to the WBI. Adult cynomolgus monkeys received fractionated WBI with the total dose of 15Gy and 30Gy. The animals were administrated with BrdU to label proliferating cells five days after the WBI and sacrificed on the next day. The density of proliferating cells in the hippocampus was significantly increased (ANOVA, F=23, df=2, 9, p=0.0003). Comparing to the sham-irradiation, proliferation were elevated by 6.3 and 12.6 times with 15Gy and 30Gy, respectively. However, there is no BrdU (+) cells co-labeled with Iba1, which is a marker of microglia. The radiation-induced cell proliferation in the hippocampus may play a contributory role in the pathogenesis of late delayed cognitive dysfunction after the WBI.
