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Radiation induces progenitor cell death, microglia activation, and blood-brain barrier damage in the juvenile rat cerebellum

Journal article
Authors K. Zhou
Martina Boström
C. Joakim Ek
T. Li
C. C. Xie
Y. R. Xu
Y. Y. Sun
K. Blomgren
C. L. Zhu
Published in Scientific Reports
Volume 7
ISSN 2045-2322
Publication year 2017
Published at Institute of Neuroscience and Physiology
Institute of Clinical Sciences, Department of Oncology
Language en
Links doi.org/10.1038/srep46181
Keywords posterior-fossa tumors, young-mouse brain, adult hippocampal, neurogenesis, mitochondrial-dna damage, ionizing-radiation, hypoxia-ischemia, oxidative stress, neurovascular niche, x-irradiation, long-term
Subject categories Cancer and Oncology

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.

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