Encephalic radiation therapy delivered at a conventional dose rate (CONV, 0.1–2.0 Gy/min) elicits a variety of temporally distinct damage signatures that invariably involve persistent indications of neuroinflammation. Past work has shown an involvement of both the innate and adaptive immune systems in modulating the central nervous system (CNS) radiation injury response, where elevations in astrogliosis, microgliosis and cytokine signaling define a complex pattern of normal tissue toxicities that never completely resolve. These side effects constitute a major limitation in the management of CNS malignancies in both adult and pediatric patients. The advent of a novel ultra-high dose-rate irradiation modality termed FLASH radiotherapy (FLASH-RT, instantaneous dose rates ≥10⁶ Gy/s; 10 Gy delivered in 1–10 pulses of 1.8 µs) has been reported to minimize a range of normal tissue toxicities typically concurrent with CONV exposures, an effect that has been coined the “FLASH effect.” Since the FLASH effect has now been found to significantly limit persistent inflammatory signatures in the brain, we sought to further elucidate whether changes in astrogliosis might account for the differential dose-rate response of the irradiated brain. Here we report that markers selected for activated astrogliosis and immune signaling in the brain (glial fibrillary acidic protein, GFAP; toll-like receptor 4, TLR4) are expressed at reduced levels after FLASH irradiation compared to CONV-irradiated animals. Interestingly, while FLASH-RT did not induce astrogliosis and TLR4, the expression level of complement C1q and C3 were found to be elevated in both FLASH and CONV irradiation modalities compared to the control. Although functional outcomes in the CNS remain to be cross-validated in response to the specific changes in protein expression reported, the data provide compelling evidence that distinguishes the dose-rate response of normal tissue injury in the irradiated brain.

以常规剂量率（CONV，0.1–2.0 Gy / min）进行的脑放射治疗会引起多种时间上不同的损伤特征，这些特征总是涉及神经炎症的持续指征。过去的工作表明，先天性免疫系统和适应性免疫系统均参与调节中枢神经系统（CNS）辐射损伤反应，其中星形胶质细胞增多症，小胶质细胞增多症和细胞因子信号传导的升高定义了无法完全解决的复杂的正常组织毒性模式。这些副作用构成了成人和小儿患者中枢神经系统恶性肿瘤治疗的主要限制。一种新颖的超高剂量率照射模态的出现称为FLASH放疗（FLASH-RT，瞬时剂量率≥10 ⁶Gy / s；据报道，以1.8 µs的1–10个脉冲传递10 Gy可使典型的CONV暴露同时引起的正常组织毒性最小化，这种效应被称为“ FLASH效应”。。” 由于现已发现FLASH效应显着限制了大脑中持续存在的炎症信号，因此我们试图进一步阐明星形胶质变的变化是否可能解释了受辐照的大脑的不同剂量率反应。在这里，我们报道，与CONV辐照动物相比，FLASH辐照后的大脑中活化星形胶质细胞增多症和免疫信号选择的标记物（神经胶质纤维酸性蛋白GFAP； toll样受体4，TLR4）以降低的水平表达。有趣的是，虽然FLASH-RT不会诱导星形胶质细胞增生和TLR4，但与对照相比，FLASH和CONV照射方式中补体C1q和C3的表达水平均升高。