Radiation therapy (RT) is a crucial treatment modality for central nervous system (CNS) tumors but toxicity to healthy CNS tissues remains a challenge. Additionally, environmental exposure to radiation during nuclear catastrophes or space travel presents a risk of CNS toxicity. However, the underlying mechanisms of radiation-induced CNS toxicity are not fully understood. Neural progenitor cells (NPCs) are highly radiosensitive, resulting in decreased neurogenesis in the hippocampus. This study aimed to characterize a novel platform utilizing rat NPCs cultured as 3D neurospheres (NSps) to screen the safety and efficacy of experimental drugs with and without radiation exposure. The effect of radiation on NSp growth and differentiation was assessed by measuring sphere volume and the expression of neuronal differentiation markers Nestin and GFAP and proliferation marker Ki67. Radiation exposure inhibited NSp growth, decreased proliferation, and increased GFAP expression, indicating astrocytic differentiation. RNA sequencing analysis supported these findings, showing upregulation of Notch, BMP2/4, S100b, and GFAP gene expression during astrogenesis. By recapitulating radiation-induced toxicity and astrocytic differentiation, this single-NSp culture system provides a high-throughput preclinical model for assessing the effects of various radiation modalities and evaluates the safety and efficacy of potential therapeutic interventions in combination with radiation.
放射治疗是中枢神经系统肿瘤的关键治疗手段，但对健康中枢神经组织的毒性作用仍是临床面临的挑战。此外，核事故或太空航行中的环境辐射暴露也存在中枢神经系统毒性风险。然而，辐射诱导中枢神经系统毒性的潜在机制尚未完全阐明。神经祖细胞具有高度辐射敏感性，可导致海马区神经发生减少。本研究旨在建立一种基于大鼠神经祖细胞三维神经球培养的新型平台，用于筛选实验性药物在辐射暴露条件下的安全性与有效性。通过测量神经球体积、神经元分化标志物巢蛋白与胶质纤维酸性蛋白以及增殖标志物Ki67的表达水平，评估辐射对神经球生长与分化的影响。辐射暴露可抑制神经球生长、降低增殖活性并增加胶质纤维酸性蛋白表达，提示星形胶质细胞分化趋势。RNA测序分析结果支持上述发现，显示星形胶质细胞生成过程中Notch信号通路、BMP2/4、S100b及胶质纤维酸性蛋白基因表达上调。该单神经球培养体系通过重现辐射诱导的毒性反应与星形胶质细胞分化过程，为评估不同辐射模式的影响提供了高通量临床前模型，并可用于评价潜在治疗干预措施联合放射治疗的安全性与有效性。
肿瘤(癌症)患者之家