Many factors contribute to the health risks encountered by astronauts on missions outside Earth’s atmosphere. Spaceflight‐induced potential adverse neurovascular damage and late neurodegeneration are a chief concern. The goal of the present study was to characterize the effects of spaceflight on oxidative damage in the mouse brain and its impact on blood‐brain barrier (BBB) integrity. Ten‐week‐old male C57BL/6 mice were launched to the International Space Station (ISS) for 35 days as part of Space‐X 12 mission. Ground control (GC) mice were maintained on Earth in flight hardware cages. Within 38 ± 4 hours after returning from the ISS, mice were euthanized and brain tissues were collected for analysis. Quantitative assessment of brain tissue demonstrated that spaceflight caused an up to 2.2‐fold increase in apoptosis in the hippocampus compared to the control group. Immunohistochemical analysis of the mouse brain revealed an increased expression of aquaporin4 (AQP4) in the flight hippocampus compared to the controls. There was also a significant increase in the expression of platelet endothelial cell adhesion molecule‐1 (PECAM‐1) and a decrease in the expression of the BBB‐related tight junction protein, Zonula occludens‐1 (ZO‐1). These results indicate a disturbance of BBB integrity. Quantitative proteomic analysis showed significant alterations in pathways responsible for neurovascular integrity, mitochondrial function, neuronal structure, protein/organelle transport, and metabolism in the brain after spaceflight. Changes in pathways associated with adhesion and molecular remodeling were also documented. These data indicate that long‐term spaceflight may have pathological and functional consequences associated with neurovascular damage and late neurodegeneration.

中文翻译：

---

太空飞行对小鼠模型血脑屏障完整性造成氧化损伤

许多因素都会导致宇航员在地球大气层之外执行任务时遇到健康风险。太空飞行引起的潜在不良神经血管损伤和晚期神经变性是主要问题。本研究的目的是表征太空飞行对小鼠大脑氧化损伤的影响及其对血脑屏障（BBB）完整性的影响。作为 Space-X 12 任务的一部分，十周大的雄性 C57BL/6 小鼠被发射到国际空间站 (ISS) 为期 35 天。地面控制（GC）小鼠被饲养在地球上的飞行硬件笼中。从国际空间站返回后 38±4 小时内，对小鼠实施安乐死，并收集脑组织进行分析。对脑组织的定量评估表明，与对照组相比，太空飞行导致海马体细胞凋亡增加高达 2.2 倍。小鼠大脑的免疫组织化学分析显示，与对照组相比，飞行海马体中水通道蛋白 4 (AQP4) 的表达增加。血小板内皮细胞粘附分子-1 (PECAM-1) 的表达也显着增加，而 BBB 相关紧密连接蛋白闭合小带-1 (ZO-1) 的表达减少。这些结果表明 BBB 完整性受到干扰。定量蛋白质组分析显示，太空飞行后，负责神经血管完整性、线粒体功能、神经元结构、蛋白质/细胞器运输和大脑代谢的通路发生了显着变化。还记录了与粘附和分子重塑相关的途径的变化。这些数据表明，长期太空飞行可能会产生与神经血管损伤和晚期神经变性相关的病理和功能后果。