高压氧暴露导致啮齿动物的血脑屏障破裂。

Exposure to hyperbaric O levels leads to blood-brain barrier breakdown in rodents.

机构信息

Israel Naval Medical Institute, P.O. Box 8040, Haifa, 31080, Israel.

Research Institute of Galilee Medical Center, P.O.Box 21, Nahariya, 22100, Israel.

出版信息

Fluids Barriers CNS. 2024 May 16;21(1):41. doi: 10.1186/s12987-024-00543-7.

DOI:10.1186/s12987-024-00543-7

PMID:38755589

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11097412/

Abstract

INTRODUCTION

Hyperbaric oxygen has been used as a medical treatment tool in hyperbaric chambers and is an integral part of professional and combat divers' activity. In extreme cases, exposure to hyperbaric oxygen can develop central nervous system oxygen toxicity (CNS-OT), which leads to seizures and eventually death. CNS-OT is caused by neuronal hyperactivity due to high oxygen levels, potentially damaging brain cells including the blood-brain barrier (BBB). However, the effect of hyperbaric oxygen levels on the healthy BBB has not been characterized directly yet.

METHODS

Six or three different groups of ~ eight rats or mice, respectively, were exposed to increasing levels of partial pressure of oxygen (0.21 to 5 ATA) in a hyperbaric chamber, followed by MRI scanning with gadolinium. Statistical significance (adjusted p-value ≤ 0.05) was assessed using linear regression and ordinary one-way (rats) or two-way (mice) ANOVA with correction of multiple comparison tests. In rats, the effect of 100% oxygen at 5 ATA was independently validated using FITC-Dextran (5 kDa). Statistical significance (p-value ≤ 0.05) was assessed using Welch's t-test and effect size was calculated by Cohen's D.

RESULTS

In rats, analyzed MRI scans showed a significant trend of increase in the % gadolinium in brain tissues as a result of hyperbaric oxygen pressures (p-value = 0.0079). The most significant increase was measured at 4 ATA compared to air (adjusted p-value = 0.0461). Significant increased FITC-Dextran levels were measured in the rats' brains under 100% oxygen at 5 ATA versus air (p-value = 0.0327; Effect size = 2.0). In mice, a significant increase in gadolinium penetration into the hippocampus and frontal cortex was measured over time (adjusted p-value < 0.05) under 100% oxygen at 3 and 5 ATA versus air, and between the treatments (adjusted p-value < 0.0001).

CONCLUSIONS

The BBB is increasingly disrupted due to higher levels of hyperbaric oxygen in rodents, indicating a direct relation between hyperbaric oxygen and BBB dysregulation for the first time. We suggest considering this risk in different diving activities, and protocols using a hyperbaric chamber. On the other hand, this study highlights the potential therapeutic usage of hyperbaric oxygen for controlled drug delivery through the BBB into brain tissues in different brain-related diseases.

摘要

简介

高压氧已被用作高压舱中的医疗治疗工具，是专业潜水员和作战潜水员活动的重要组成部分。在极端情况下，暴露于高压氧会导致中枢神经系统氧中毒（CNS-OT），从而引发癫痫发作，最终导致死亡。CNS-OT 是由于高氧水平引起的神经元过度活跃引起的，可能会损害包括血脑屏障（BBB）在内的脑细胞。然而，高压氧水平对健康 BBB 的影响尚未直接表征。

方法

分别将六组或三组约 8 只大鼠或小鼠置于高压舱中，接受不同水平的氧气分压（0.21 至 5ATA），随后用钆造影进行 MRI 扫描。使用线性回归和普通的大鼠单向（大鼠）或小鼠双向（小鼠）方差分析评估统计学意义（调整后的 p 值≤0.05），并校正多重比较检验。在大鼠中，使用 FITC-葡聚糖（5kDa）独立验证了 5ATA 时 100%氧气的效果。使用 Welch 的 t 检验评估统计学意义（p 值≤0.05），并通过 Cohen 的 D 计算效应大小。

结果

在大鼠中，分析后的 MRI 扫描显示，由于高压氧压力，脑组织中的 %钆含量呈显著增加趋势（p 值=0.0079）。与空气相比，在 4ATA 时测量到的增加最为显著（调整后的 p 值=0.0461）。在 5ATA 时，与空气相比，大鼠大脑中的 FITC-葡聚糖水平显著升高（p 值=0.0327；效应大小=2.0）。在小鼠中，在 3 和 5ATA 时，与空气相比，100%氧气下海马体和额叶皮层的钆渗透随时间呈显著增加趋势（调整后的 p 值<0.05），并且在处理之间也呈显著增加趋势（调整后的 p 值<0.0001）。