Toxicity to central nervous system tissues is the common side effects for radiotherapy of brain tumor. The radiation toxicity has been thought to be related to the damage of cerebral endothelium. However, because of lacking a suitable high-resolution vivo model, cellular response of cerebral capillaries to radiation remained unclear. Here, we present the flk:eGFP transgenic zebrafish larvae as a feasible model to study the radiation toxicity to cerebral capillary. We showed that, in living zebrafish larvae, radiation could induce acute cerebral capillary shrinkage and blood-flow obstruction, resulting brain hypoxia and glycolysis retardant. Although in vivo neuron damage was also observed after the radiation exposure, further investigation found that they didn't response to the same dosage of radiation in vitro, indicating that radiation induced neuron damage was a secondary-effect of cerebral vascular function damage. In addition, transgenic labeling and qPCR results showed that the radiation-induced acute cerebral endothelial damage was correlated with intensive endothelial autophagy. Different autophagy inhibitors could significantly alleviate the radiation-induced cerebral capillary damage and prolong the survival of zebrafish larvae. Therefore, we showed that radiation could directly damage cerebral capillary, resulting to blood flow deficiency and neuron death, which suggested endothelial autophagy as a potential target for radiation-induced brain toxicity.

中文翻译：

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内皮细胞自噬：辐射诱发的脑毛细血管损害的有效目标。

对中枢神经系统组织的毒性是脑肿瘤放疗的常见副作用。辐射毒性被认为与脑内皮损伤有关。然而，由于缺乏合适的高分辨率体内模型，大脑毛细血管对辐射的细胞反应仍然不清楚。在这里，我们提出了flk：eGFP转基因斑马鱼幼虫，作为研究对脑毛细血管辐射毒性的可行模型。我们发现，在活的斑马鱼幼虫中，辐射可引起急性脑毛细血管收缩和血流阻塞，从而导致脑缺氧和糖酵解延迟。尽管在放射线照射后也观察到了体内神经元损伤，但进一步的研究发现它们在体外对相同剂量的放射线没有反应，表明放射线诱发的神经元损伤是脑血管功能损伤的次要作用。此外，转基因标记和qPCR结果表明，放射线诱发的急性脑内皮损伤与强烈的内皮自噬有关。不同的自噬抑制剂可以显着减轻辐射引起的脑毛细血管损害，并延长斑马鱼幼虫的存活时间。因此，我们发现放射线可直接损害脑毛细血管，导致血流不足和神经元死亡，这表明内皮细胞自噬是放射线诱发的脑毒性的潜在靶标。转基因标记和qPCR结果表明，放射线诱发的急性脑内皮损伤与强烈的内皮自噬有关。不同的自噬抑制剂可以显着减轻辐射引起的脑毛细血管损害，并延长斑马鱼幼虫的存活时间。因此，我们发现放射线可直接损害脑毛细血管，导致血流不足和神经元死亡，这表明内皮细胞自噬是放射线诱发的脑毒性的潜在靶标。转基因标记和qPCR结果表明，放射线诱发的急性脑内皮损伤与强烈的内皮自噬有关。不同的自噬抑制剂可以显着减轻辐射引起的脑毛细血管损害，并延长斑马鱼幼虫的存活时间。因此，我们发现放射线可直接损害脑毛细血管，导致血流不足和神经元死亡，这表明内皮细胞自噬是放射线诱发的脑毒性的潜在靶标。