title: Radiation induces progenitor cell death, microglia activation, and blood-brain barrier damage in the juvenile rat cerebellum.
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.
authors.affiliation: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.|Karolinska Institutet, Department of Women's and Children's Health, Stockholm, Sweden.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.|Department of Oncology, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Martina
authors.initials: M
authors.lastname: Boström
authors.affiliation: Perinatal Center, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: C Joakim
authors.initials: CJ
authors.lastname: Ek
authors.affiliation: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.|Department of Pediatrics, Zhengzhou Children's Hospital, Zhengzhou, China.|Henan Key Laboratory of Child Brain Injury, Henan International Joint Laboratory of Child Brain Injury, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.|Karolinska Institutet, Department of Women's and Children's Health, Stockholm, Sweden.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Xie
authors.affiliation: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.|Henan Key Laboratory of Child Brain Injury, Henan International Joint Laboratory of Child Brain Injury, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.|Henan Key Laboratory of Child Brain Injury, Henan International Joint Laboratory of Child Brain Injury, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Karolinska Institutet, Department of Women's and Children's Health, Stockholm, Sweden.|Department of Pediatric Oncology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Klas
authors.initials: K
authors.lastname: Blomgren
authors.affiliation: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.|Henan Key Laboratory of Child Brain Injury, Henan International Joint Laboratory of Child Brain Injury, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Changlian
authors.initials: C
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology* / Q000528:radiation effects*; D016923:Cell Death / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D002531:Cerebellum / Q000098:blood supply / Q000473:pathology* / Q000528:radiation effects; D002560:Cerebrovascular Circulation / Q000528:radiation effects; D007249:Inflammation / Q000473:pathology; D008297:Male; D017628:Microglia / Q000473:pathology* / Q000528:radiation effects*; D063154:Mitochondrial Dynamics / Q000528:radiation effects; D018384:Oxidative Stress / Q000528:radiation effects; D011827:Radiation; D017208:Rats, Wistar; D013234:Stem Cells / Q000473:pathology* / Q000528:radiation effects*