Ruifrok A C, Stephens L C, van der Kogel A J
Institute of Radiotherapy, University of Nijmegen, The Netherlands.
Int J Radiat Oncol Biol Phys. 1994 Apr 30;29(1):73-9. doi: 10.1016/0360-3016(94)90228-3.
The investigation of the age dependent single-dose radiation tolerance, latency to radiation myelopathy, and the histopathological changes after irradiation of the rat cervical spinal cord.
Rats, ages 1-18 weeks, were irradiated with graded single doses of 4 MV photons to the cervical spinal cord. When the rats showed definite signs of paresis of the forelegs, they were killed and processed for histological examination.
The radiation dose in paresis due to white matter damage in 50% of the animals (ED50) after single dose irradiation was about 21.5 Gy at all ages > or = 2 weeks (mean 21.4 (mean 21.4 Gy; 95% CI 21.0, 21.7 Gy). Only the ED50 at 1 week was significantly lower (19.5 Gy; 18.7, 20.3 Gy). The latency to the development of paresis clearly changed with the age at irradiation, from about 2 weeks after irradiation at 1 week to 6-8 months after irradiation at age > or = 8 weeks. The white matter damage was similar in all symptomatic animals studied. The most prominent were areas with diffuse demyelination and swollen axons, often with focal necrosis, accompanied by glial reaction. This was observed in all symptomatic animals, irrespective of the age at irradiation. Expression of vascular damage appeared to depend on the age at irradiation. No vascular damage was observed in the rats irradiated at 1 week, clearly altered blood vessels were seen in animals symptomatic 10 weeks after irradiation at > or = 3 weeks, and vascular necrosis occurred after > or = 6 months in some rats irradiated at > or = 8 weeks.
Although the latency to myelopathy is clearly age dependent, single dose tolerance is not age dependent at age > or = 2 weeks in the rat cervical spinal cord. The white matter damage is similar in all symptomatic animals studied, but the vasculopathies appear to be influenced by the age at irradiation. It is concluded that white matter damage and vascular damage are separate phenomena contributing to the development of radiation myelopathy, expression of which may depend on the radiation dose applied and the age at irradiation.
研究大鼠颈段脊髓单剂量辐射耐受性的年龄依赖性、放射性脊髓病的潜伏期以及照射后的组织病理学变化。
对1至18周龄的大鼠颈段脊髓进行4兆伏光子的分级单剂量照射。当大鼠出现明确的前肢轻瘫体征时，将其处死并进行组织学检查。
在所有年龄≥2周的动物中，单剂量照射后因白质损伤导致50%的动物出现轻瘫的辐射剂量（ED50）约为21.5 Gy（平均21.4 Gy；95%可信区间21.0，21.7 Gy）。仅1周龄时的ED50显著较低（19.5 Gy；18.7，20.3 Gy）。轻瘫发生的潜伏期随照射时的年龄明显变化，从1周龄照射后约2周变为≥8周龄照射后6至8个月。在所有研究的有症状动物中，白质损伤相似。最显著的是弥漫性脱髓鞘和轴突肿胀的区域，常伴有局灶性坏死，并伴有胶质反应。在所有有症状动物中均观察到这种情况，与照射时的年龄无关。血管损伤的表现似乎取决于照射时的年龄。1周龄照射的大鼠未观察到血管损伤，≥3周龄照射后10周出现症状的动物可见明显改变的血管，≥8周龄照射的一些大鼠在≥6个月后出现血管坏死。
虽然放射性脊髓病的潜伏期明显依赖于年龄，但在大鼠颈段脊髓中，≥2周龄时单剂量耐受性不依赖于年龄。在所有研究的有症状动物中，白质损伤相似，但血管病变似乎受照射时年龄的影响。得出的结论是白质损伤和血管损伤是导致放射性脊髓病发生的不同现象，其表现可能取决于所施加的辐射剂量和照射时的年龄。
