PDF(Pubmed)
Abstract：
Evidence shows that ultra-high dose-rate FLASH-radiotherapy (FLASH-RT) protects against normal tissue complications and functional decrements in the irradiated brain. Past work has shown that radiation-induced cognitive impairment, neuroinflammation and reduced structural complexity of granule cell neurons were not observed to the same extent after FLASH-RT (> MGy/s) compared to conventional dose-rate (CONV, 0.1 Gy/s) delivery. To explore the sensitivity of different neuronal populations to cranial irradiation and dose-rate modulation, hippocampal CA1 and medial prefrontal cortex (PFC) pyramidal neurons were analyzed by electron and confocal microscopy. Neuron ultrastructural analyses by electron microscopy after 10 Gy FLASH- or CONV-RT exposures indicated that irradiation had little impact on dendritic complexity and synapse density in the CA1, but did increase length and head diameter of smaller non-perforated synapses. Similarly, irradiation caused no change in PFC prelimbic/infralimbic axospinous synapse density, but reductions in non-perforated synapse diameters. While irradiation resulted in thinner myelin sheaths compared to controls, none of these metrics were dose-rate sensitive. Analysis of fluorescently labeled CA1 neurons revealed no radiation-induced or dose-rate-dependent changes in overall dendritic complexity or spine density, in contrast to our past analysis of granule cell neurons. Super-resolution confocal microscopy following a clinical dosing paradigm (3×10Gy) showed significant reductions in excitatory vesicular glutamate transporter 1 and inhibitory vesicular GABA transporter puncta density within the CA1 that were largely dose-rate independent. Collectively, these data reveal that, compared to granule cell neurons, CA1 and mPFC neurons are more radioresistant irrespective of radiation dose-rate.
摘要：
有证据表明，超高剂量率FLASH放射疗法（FLASH-RT）可以防止正常组织并发症和受照射的大脑功能下降。过去的工作表明，辐射引起的认知障碍，与常规剂量率（CONV，0.1Gy/s)交货。探讨不同神经元群体对头颅照射和剂量率调制的敏感性,通过电子和共聚焦显微镜分析海马CA1和内侧前额叶皮质（PFC）锥体神经元。10GyFLASH或CONV-RT暴露后通过电子显微镜进行的神经元超微结构分析表明，辐照对CA1中的树突复杂性和突触密度影响很小，但确实增加了较小的非穿孔突触的长度和头部直径。同样，辐照未引起PFC前边缘/外边缘轴突突触密度的变化，而是减少未穿孔的突触直径。与对照组相比，照射导致髓鞘变薄，这些指标均不对剂量率敏感。对荧光标记的CA1神经元的分析显示，总体树突复杂性或脊柱密度没有辐射诱导或剂量率依赖性变化，与我们过去对颗粒细胞神经元的分析相反.临床给药范例（3×10Gy）后的超分辨率共聚焦显微镜显示，CA1内的兴奋性囊泡谷氨酸转运蛋白1和抑制性囊泡GABA转运蛋白点密度显着降低，这在很大程度上与剂量率无关。总的来说，这些数据表明，与颗粒细胞神经元相比，与辐射剂量率无关，CA1和mPFC神经元对辐射的抵抗力更强。
