Abstract
BackgroundBrain radiation exposure, in particular, radiotherapy, can induce cognitive impairment in patients, with significant effects persisting for the rest of their life. However, the main mechanisms leading to this adverse event remain largely unknown. A study of radiation-induced injury to multiple brain regions, focused on the hippocampus, may shed light on neuroanatomic bases of neurocognitive impairments in patients. Hence, we irradiated BALB/c mice (male and female) at postnatal day 3 (P3), day 10 (P10), and day 21 (P21) and investigated the long-term radiation effect on brain MRI changes and hippocampal neurogenesis.ResultsWe found characteristic brain volume reductions in the hippocampus, olfactory bulbs, the cerebellar hemisphere, cerebellar white matter (WM) and cerebellar vermis WM, cingulate, occipital and frontal cortices, cerebellar flocculonodular WM, parietal region, endopiriform claustrum, and entorhinal cortex after irradiation with 5 Gy at P3. Irradiation at P10 induced significant volume reduction in the cerebellum, parietal region, cingulate region, and olfactory bulbs, whereas the reduction of the volume in the entorhinal, parietal, insular, and frontal cortices was demonstrated after irradiation at P21. Immunohistochemical study with cell division marker Ki67 and immature marker doublecortin (DCX) indicated the reduced cell division and genesis of new neurons in the subgranular zone of the dentate gyrus in the hippocampus after irradiation at all three postnatal days, but the reduction of total granule cells in the stratum granulosun was found after irradiation at P3 and P10.ConclusionsThe early life radiation exposure during different developmental stages induces varied brain pathophysiological changes which may be related to the development of neurological and neuropsychological disorders later in life.
Highlights
Brain radiation exposure, in particular, radiotherapy, can induce cognitive impairment in patients, with significant effects persisting for the rest of their life
A total of 28 mice was used in this study. These animals were divided into four groups based on litters, i.e., the normal control group (n = 7, 2 from P3 group, 2 from P10 group, and 3 from P21 group) without irradiation; The experimental groups were whole-body irradiated with 5 Gy at postnatal day 3 (P3, n = 9), 10 (P10, n = 7), and 21 (P21, n = 5) using the Gamma-Irradiator BIOBEAM8000 (GammaService Medical GmbH, Leipzig, Germany)
In the present mouse model, we showed significant volume changes in the hippocampus, and cerebellar flocculonodular lobe when animals were irradiated at P3, but not P10 and P21, suggesting that radiation exposure at different early postnatal days may induce varied brain pathological changes and subsequent neurological and neuropsychological disorders in the later stages of animal or human life
Summary
In particular, radiotherapy, can induce cognitive impairment in patients, with significant effects persisting for the rest of their life. Radiotherapy has been used to treat brain tumors and prevent cancer cell metastasis from other organs to the brain, but it induces brain structural and functional changes, which causes lifelong problems with severe societal and economic impact, in particular, in young patients. Brain structural changes such as volume reduction, vascular dilatation and permeability, and white matter pathology ranging from demyelination to coagulative necrosis can be detected by magnetic resonance imaging. In the present study, we aimed to develop MR imaging biomarkers to monitor radiation-induced brain damage and correlate brain neurogenesis alterations to imaging changes and neurological and neuropsychological disorders
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