低氧血症对大鼠脉络丛和脑脊液系统产生有害影响。

Hypoxemia exerts detrimental effects on the choroid plexuses and cerebrospinal fluid system in rats.

作者信息

Barakat Rawan, Al-Sarraf Hameed, Redzic Zoran

机构信息

Department of Physiology, College of Medicine, Kuwait University, P.O. Box 24923, 13110, Safat, Kuwait.

出版信息

Fluids Barriers CNS. 2025 Mar 12;22(1):27. doi: 10.1186/s12987-024-00613-w.

DOI:10.1186/s12987-024-00613-w

PMID:40075475

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11905537/

Abstract

BACKGROUND

Hypoxemia can cause secondary acute brain injury, but the mechanisms behind it are not entirely clear and could involve disturbances in the brain extracellular fluids. We aimed to explore the effects of hypoxemia on the choroid plexus (CPs) and cerebrospinal fluid (CSF) system in rats.

METHODS

Male Sprague Dawley rats were kept in O control in vivo cabinet with either 21% (normoxia) or 8% O (hypoxemia) for up to 48 h. In some cases, signaling of selected cytokines was inhibited prior to hypoxemia. CSF and blood samples were collected by Cisterna Magna puncture and through venous catheters, respectively. The percentages of dead cells in the CPs and ependymal layers (EL) after hypoxemia or normoxia was estimated using TUNEL staining. CP's ultrastructure was analyzed by transmission electron microscopy. Protein concentration in the CSF and plasma was measured and the CSF albumin-to-total protein ratios were estimated. Concentrations of hypoxia-related cytokines in the CSF and plasma samples were estimated using the multiplex immunoassay. Data was analyzed by one-way ANOVA followed by either Bonferroni or Tukey's multiple comparison tests, or Student's t-test. Results are presented as mean ± SD; p < 0.05 was considered statistically significant.

RESULTS

Duration of hypoxemia exerted significant effects on the cell viability in the CPs (p < 0.01) and EL (p < 0.01) and caused apoptosis-related changes in the CP. Hypoxemia had significant effects on the protein concentration in the CSF (p < 0.05), but not in plasma (p > 0.05), with a significant increase in the CSF albumin-to-total protein ratio after 6 h hypoxemia (p < 0.05). Thirty-two cytokines were detected in the CSF. Hypoxemia caused a statistically significant reduction in the concentrations of 12 cytokines, while concentrations of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) increased significantly. Exposure to hypoxemia after inhibitions of EPO, VEGF, or tumor necrosis factor alpha (TNFα) signaling resulted in more dead cells (p < 0.01), less dead cells (p < 0.01) and more dead cells (p < 0.01) in the CPs, respectively, when compared to the number of dead cells when these cytokines were not inhibited. The density of macrophages in the CPs decreased significantly during hypoxemia; that effect was cancelled out by TNFα inhibition.

CONCLUSION

Hypoxemia had detrimental effects on the CPs and CSF system, which was modulated by hypoxia- and inflammation-related cytokines.

摘要

背景

低氧血症可导致继发性急性脑损伤，但其背后的机制尚不完全清楚，可能涉及脑细胞外液的紊乱。我们旨在探讨低氧血症对大鼠脉络丛（CPs）和脑脊液（CSF）系统的影响。

方法

将雄性Sprague Dawley大鼠置于体内实验箱中，分别在21%（常氧）或8%氧气（低氧血症）条件下饲养长达48小时。在某些情况下，在低氧血症之前抑制选定细胞因子的信号传导。分别通过枕大池穿刺和静脉导管采集脑脊液和血液样本。使用TUNEL染色估计低氧血症或常氧血症后CPs和室管膜层（EL）中死亡细胞的百分比。通过透射电子显微镜分析CP的超微结构。测量脑脊液和血浆中的蛋白质浓度，并估计脑脊液白蛋白与总蛋白的比率。使用多重免疫测定法估计脑脊液和血浆样本中与缺氧相关的细胞因子浓度。数据通过单因素方差分析，然后进行Bonferroni或Tukey多重比较检验，或Student t检验进行分析。结果以平均值±标准差表示；p<0.05被认为具有统计学意义。

结果

低氧血症持续时间对CPs（p<0.01）和EL（p<0.01）中的细胞活力有显著影响，并导致CP中与凋亡相关的变化。低氧血症对脑脊液中的蛋白质浓度有显著影响（p<0.05），但对血浆中的蛋白质浓度无显著影响（p>0.05），低氧血症6小时后脑脊液白蛋白与总蛋白的比率显著增加（p<0.05）。在脑脊液中检测到32种细胞因子。低氧血症导致12种细胞因子的浓度在统计学上显著降低，而促红细胞生成素（EPO）和血管内皮生长因子（VEGF）的浓度显著增加。与未抑制这些细胞因子时的死亡细胞数量相比，在抑制EPO、VEGF或肿瘤坏死因子α（TNFα）信号传导后暴露于低氧血症分别导致CPs中更多的死亡细胞（p<0.01）、更少的死亡细胞（p<0.01）和更多的死亡细胞（p<0.01）。低氧血症期间CPs中巨噬细胞的密度显著降低；TNFα抑制可抵消该效应。