Center for Radiological Research, Columbia University Irving Medical Center, 630 West 168th street, VC-11-234/5, New York, NY, 10032, USA.
NASA Langley Research Center, Hampton, VA, USA.
Sci Rep. 2021 Apr 23;11(1):8845. doi: 10.1038/s41598-021-88486-z.
Radiation-induced cognitive dysfunction is increasingly recognized as an important risk for human exploration of distant planets. Mechanistically-motivated mathematical modeling helps to interpret and quantify this phenomenon. Here we considered two general mechanisms of ionizing radiation-induced damage: targeted effects (TE), caused by traversal of cells by ionizing tracks, and non-targeted effects (NTE), caused by responses of other cells to signals released by traversed cells. We compared the performances of 18 dose response model variants based on these concepts, fitted by robust nonlinear regression to a large published data set on novel object recognition testing in rats exposed to multiple space-relevant radiation types (H, C, O, Si, Ti and Fe ions), covering wide ranges of linear energy transfer (LET) (0.22-181 keV/µm) and dose (0.001-2 Gy). The best-fitting model (based on Akaike information criterion) was an NTE + TE variant where NTE saturate at low doses (~ 0.01 Gy) and occur at all tested LETs, whereas TE depend on dose linearly with a slope that increases with LET. The importance of NTE was also found by additional analyses of the data using quantile regression and random forests. These results suggest that NTE-based radiation effects on brain function are potentially important for astronaut health and for space mission risk assessments.
辐射诱导的认知功能障碍日益被认为是人类探索遥远行星的一个重要风险。基于机制的数学建模有助于解释和量化这一现象。在这里，我们考虑了两种电离辐射损伤的一般机制：靶向效应（TE），由电离轨迹穿过细胞引起，和非靶向效应（NTE），由穿过细胞释放的信号引起其他细胞的反应。我们比较了基于这些概念的 18 种剂量反应模型变体的性能，这些变体通过稳健的非线性回归拟合到一个关于大鼠新型物体识别测试的大型已发表数据集上，该数据集涵盖了广泛的线性能量转移（LET）（0.22-181 keV/μm）和剂量（0.001-2 Gy）范围。基于赤池信息量准则的最佳拟合模型（Akaike information criterion）是一种 NTE+TE 变体，其中 NTE 在低剂量（约 0.01 Gy）下饱和，并在所有测试的 LET 下发生，而 TE 则随剂量线性增加，斜率随 LET 增加而增加。通过使用分位数回归和随机森林对数据进行额外分析，也发现了 NTE 的重要性。这些结果表明，基于 NTE 的辐射对大脑功能的影响可能对宇航员的健康和太空任务风险评估很重要。
