Beijing Tong Ren Hospital, Capital Medical University, Beijing, China.
Aerospace Medical Center, Aerospace Center Hospital, Beijing, China.
Brain Behav. 2024 Sep;14(9):e3648. doi: 10.1002/brb3.3648.
The blood-cerebrospinal fluid barrier (BCSFB) comprises the choroid plexus epithelia. It is important for brain development, maintenance, function, and especially for maintaining immune homeostasis in the cerebrospinal fluid (CSF). Although previous studies have shown that the peripheral immune function of the body is impaired upon exposure to microgravity, no studies have reported changes in immune cells and cytokines in the CSF that reflect neuroimmune status. The purpose of this study is to investigate the alterations in cerebrospinal fluid (CSF) immune homeostasis induced by microgravity and its mechanisms. This research is expected to provide basic data for brain protection of astronauts during spaceflight.
The proportions of immune cells in the CSF and peripheral blood (PB) of SMG rats were analyzed using flow cytometry. Immune function was evaluated by measuring cytokine concentrations using the Luminex method. The histomorphology and ultrastructure of the choroid plexus epithelia were determined. The concentrations of intercellular junction proteins in choroid plexus epithelial cells, including vascular endothelial-cadherin (VE-cadherin), zonula occludens 1 (ZO-1), Claudin-1 and occludin, were detected using western blotting and immunofluorescence staining to characterize BCSFB injury.
We found that SMG caused significant changes in the proportion of CD4 and CD8 T cells in the CSF and a significant increase in the levels of cytokines (GRO/KC, IL-18, MCP-1, and RANTES). In the PB, there was a significant decrease in the proportion of T cells and NKT cells and a significant increase in cytokine levels (GRO/KC, IL-18, MCP-1, and TNF-α). Additionally, we observed that the trends in immune markers in the PB and CSF were synchronized within specific SMG durations, suggesting that longer SMG periods (≥21 days) have a more pronounced impact on immune markers. Furthermore, 21d-SMG resulted in ultrastructural disruption and downregulated expression of intercellular junction proteins in rat choroid plexus epithelial cells.
We found that SMG disrupts the BCSFB and affects the CSF immune homeostasis. This study provides new insights into the health protection of astronauts during spaceflight.
血脑屏障（BCSFB）由脉络丛上皮细胞组成。它对于大脑的发育、维持、功能非常重要，特别是对于维持脑脊液（CSF）中的免疫内稳。尽管先前的研究表明，身体的外周免疫功能在暴露于微重力下会受到损害，但没有研究报道反映神经免疫状态的 CSF 中免疫细胞和细胞因子的变化。本研究旨在探讨微重力诱导的脑脊液（CSF）免疫内稳态的改变及其机制。这项研究有望为宇航员在太空飞行期间的大脑保护提供基础数据。
采用流式细胞术分析 SMG 大鼠 CSF 和外周血（PB）中免疫细胞的比例。通过使用 Luminex 方法测量细胞因子浓度来评估免疫功能。测定脉络丛上皮细胞的组织形态和超微结构。采用 Western blot 和免疫荧光染色检测细胞间连接蛋白在脉络丛上皮细胞中的浓度，包括血管内皮钙黏蛋白（VE-cadherin）、闭合蛋白 1（ZO-1）、Claudin-1 和闭合蛋白，以表征 BCSFB 损伤。
我们发现，SMG 导致 CSF 中 CD4 和 CD8 T 细胞的比例发生显著变化，细胞因子（GRO/KC、IL-18、MCP-1 和 RANTES）水平显著升高。在 PB 中，T 细胞和 NKT 细胞的比例显著下降，细胞因子水平（GRO/KC、IL-18、MCP-1 和 TNF-α）显著升高。此外，我们观察到 PB 和 CSF 中的免疫标志物趋势在特定的 SMG 持续时间内同步，这表明较长的 SMG 时间（≥21 天）对免疫标志物的影响更为明显。此外，21d-SMG 导致大鼠脉络丛上皮细胞超微结构破坏和细胞间连接蛋白表达下调。
我们发现 SMG 破坏了 BCSFB，并影响了 CSF 免疫内稳态。本研究为宇航员在太空飞行期间的健康保护提供了新的见解。
