Abstract
Posterior fossa tumors are the most common childhood intracranial tumors, and radiotherapy is one of the most effective treatments. However, irradiation induces long-term adverse effects that can have significant negative impacts on the patient’s quality of life. The purpose of this study was to characterize irradiation-induced cellular and molecular changes in the cerebellum. We found that irradiation-induced cell death occurred mainly in the external germinal layer (EGL) of the juvenile rat cerebellum. The number of proliferating cells in the EGL decreased, and 82.9% of them died within 24 h after irradiation. Furthermore, irradiation induced oxidative stress, microglia accumulation, and inflammation in the cerebellum. Interestingly, blood-brain barrier damage and blood flow reduction was considerably more pronounced in the cerebellum compared to other brain regions. The cerebellar volume decreased by 39% and the migration of proliferating cells to the internal granule layer decreased by 87.5% at 16 weeks after irradiation. In the light of recent studies demonstrating that the cerebellum is important not only for motor functions, but also for cognition, and since treatment of posterior fossa tumors in children typically results in debilitating cognitive deficits, this differential susceptibility of the cerebellum to irradiation should be taken into consideration for future protective strategies.
Highlights
Cell death in the cerebellum was detected by TUNEL (Fig. 1A), labeling mainly cells located in the external germinal layer (EGL) in the irradiated brains (Fig. 1A, right panels)
The total number of TUNEL-labeled cells was increased significantly at both 6 h and 24 h after irradiation compared with non-irradiated controls, with the greatest increase observed at the earlier time point (Fig. 1B)
Based on H&E stained sections, the volume of the EGL increased 20.8% at 6 h after irradiation followed by a 52.9% decrease at 24 h after irradiation compared to controls (Fig. 1C)
Summary
The purpose of this study was to characterize irradiation-induced cellular and molecular changes in the cerebellum. The purpose of this study was to define both short-term and long-term pathological changes in the cerebellum and to investigate possible mechanisms after cranial irradiation in juvenile rats
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