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Irradiation of Neurons with High-Energy Charged Particles: An In Silico Modeling Approach

机译:用高能带电粒子辐照神经元:计算机模拟方法

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摘要

In this work, a stochastic computational model of microscopic energy deposition events is used to study for the first time damage to irradiated neuronal cells of the mouse hippocampus. An extensive library of radiation tracks for different particle types is created to score energy deposition in small voxels and volume segments describing a neuron’s morphology that later are sampled for given particle fluence or dose. Methods included the construction of in silico mouse hippocampal granule cells from with spine and filopodia segments stochastically distributed along the dendritic branches. The model is tested with high-energy 56Fe, 12C, and 1H particles and electrons. Results indicate that the tree-like structure of the neuronal morphology and the microscopic dose deposition of distinct particles may lead to different outcomes when cellular injury is assessed, leading to differences in structural damage for the same absorbed dose. The significance of the microscopic dose in neuron components is to introduce specific local and global modes of cellular injury that likely contribute to spine, filopodia, and dendrite pruning, impacting cognition and possibly the collapse of the neuron. Results show that the heterogeneity of heavy particle tracks at low doses, compared to the more uniform dose distribution of electrons, juxtaposed with neuron morphology make it necessary to model the spatial dose painting for specific neuronal components. Going forward, this work can directly support the development of biophysical models of the modifications of spine and dendritic morphology observed after low dose charged particle irradiation by providing accurate descriptions of the underlying physical insults to complex neuron structures at the nano-meter scale.
机译:在这项工作中,微观能量沉积事件的随机计算模型用于首次研究对小鼠海马辐射神经元细胞的损伤。建立了广泛的辐射轨迹库,以记录不同类型的粒子,以对小体素和体积分段中的能量沉积进行评分,以描述神经元的形态,然后针对给定的粒子通量或剂量对它们进行采样。方法包括从沿着树突分支随机分布的脊柱和丝状伪足节段构建计算机化的小鼠海马颗粒细胞。使用高能 56 Fe, 12 C和 1 H粒子和电子对模型进行测试。结果表明,当评估细胞损伤时,神经元形态的树状结构和不同颗粒的微观剂量沉积可能导致不同的结果,导致相同吸收剂量下结构损伤的差异。显微剂量在神经元成分中的意义在于引入特定的局部和整体性细胞损伤模式,这些模式可能导致脊柱,丝状伪足和树突修剪,从而影响认知并可能破坏神经元。结果表明,与神经元形态并列的电子更均匀的剂量分布相比,低剂量下重粒子轨迹的异质性使得有必要对特定神经元成分的空间剂量绘制进行建模。展望未来,这项工作可以通过提供对纳米级复杂神经元结构的潜在物理损伤的准确描述,直接支持开发低剂量带电粒子辐照后观察到的脊柱和树突形态学修饰的生物物理模型。

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