Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Mouse Imaging Centre, Hospital for Sick Children, Toronto, Canada.
NMR Biomed. 2023 Dec;36(12):e5015. doi: 10.1002/nbm.5015. Epub 2023 Aug 7.
Human and animal studies suggest that exercise promotes healthy brain development and function, including promoting hippocampal growth. Childhood cancer survivors that have received cranial radiotherapy exhibit hippocampal volume deficits and are at risk of impaired cognitive function, thus they may benefit from regular exercise. While morphological changes induced by exercise have been characterized using magnetic resonance imaging (MRI) in humans and animal models, evaluation of changes across the brain through development and following cranial radiation is lacking. In this study, we used high-resolution longitudinal MRI through development to evaluate the effects of exercise in a pediatric mouse model of cranial radiation. Female mice received whole-brain radiation (7 Gy) or sham radiation (0 Gy) at an infant equivalent age (P16). One week after irradiation, mice were housed in either a regular cage or a cage equipped with a running wheel. In vivo MRI was performed prior to irradiation, and at three subsequent timepoints to evaluate the effects of radiation and exercise. We used a linear mixed-effects model to assess volumetric and cortical thickness changes. Exercise caused substantial increases in the volumes of certain brain regions, notably the hippocampus in both irradiated and nonirradiated mice. Volume increases exceeded the deficits induced by cranial irradiation. The effect of exercise and irradiation on subregional hippocampal volumes was also characterized. In addition, we characterized cortical thickness changes across development and found that it peaked between P23 and P43, depending on the region. Exercise also induced regional alterations in cortical thickness after 3 weeks of voluntary exercise, while irradiation did not substantially alter cortical thickness. Our results show that exercise has the potential to alter neuroanatomical outcomes in both irradiated and nonirradiated mice. This supports ongoing research exploring exercise as a strategy for improving neurocognitive development for children, particularly those treated with cranial radiotherapy.
人类和动物研究表明，运动促进健康的大脑发育和功能，包括促进海马体的生长。接受过颅放射治疗的儿童癌症幸存者表现出海马体体积不足，并存在认知功能受损的风险，因此他们可能受益于定期运动。虽然已经使用磁共振成像 (MRI) 在人类和动物模型中描述了运动引起的形态变化，但缺乏对整个大脑在发育过程中以及在颅放射治疗后发生的变化的评估。在这项研究中，我们使用高分辨率纵向 MRI 通过发育来评估运动对儿童颅放疗模型的影响。雌性小鼠在婴儿等效年龄 (P16) 接受全脑辐射 (7 Gy) 或假辐射 (0 Gy)。照射后一周，将小鼠饲养在普通笼子或配备跑步轮的笼子中。在照射前以及随后的三个时间点进行体内 MRI，以评估辐射和运动的影响。我们使用线性混合效应模型来评估体积和皮质厚度变化。运动导致某些大脑区域的体积显著增加，尤其是在照射和未照射的小鼠的海马体中。体积增加超过了颅照射引起的缺陷。还对运动和照射对海马体亚区体积的影响进行了特征描述。此外，我们描述了皮质厚度随时间的变化，并发现它取决于区域，在 P23 和 P43 之间达到峰值。运动还在 3 周的自愿运动后引起皮质厚度的区域性改变，而照射没有显著改变皮质厚度。我们的研究结果表明，运动有可能改变照射和未照射的小鼠的神经解剖学结果。这支持了正在进行的研究，探索运动作为改善儿童神经认知发育的策略，特别是那些接受颅放射治疗的儿童。
