暴露于高压氧水平会导致啮齿动物的血脑屏障破裂。

IF 5.9 1区 医学 Q1 NEUROSCIENCES
Yehuda M Danino, Ricarina Rabinovitz, Inbar Kirshenboim, Eilam Palzur, Chaim G Pick, Itamar Ish-Shalom, Yana Golovkin, Yehuda Arieli
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引用次数: 0

摘要

简介高压氧一直是高压氧舱中的医疗工具,也是专业潜水员和战斗潜水员活动中不可或缺的一部分。在极端情况下,接触高压氧会导致中枢神经系统氧中毒(CNS-OT),从而导致癫痫发作并最终死亡。中枢神经系统氧中毒是由于高浓度氧导致神经元过度活跃,从而可能损害脑细胞,包括血脑屏障(BBB)。然而,高压氧水平对健康 BBB 的影响尚未得到直接描述:方法:分别将六组或三组约八只大鼠或小鼠暴露于高压氧舱中不断升高的氧分压水平(0.21 至 5 ATA)中,然后用钆进行磁共振成像扫描。使用线性回归和普通单向(大鼠)或双向(小鼠)方差分析以及多重比较校正测试评估统计意义(调整后的 p 值≤ 0.05)。在大鼠中,使用 FITC-Dextran(5 kDa)独立验证了 5 ATA 时 100% 氧气的效果。统计显著性(p 值≤ 0.05)采用 Welch's t 检验,效应大小采用 Cohen's D 计算:对大鼠进行的磁共振成像扫描分析表明,高压氧导致脑组织中钆的百分比呈显著增加趋势(p 值 = 0.0079)。与空气相比,4 ATA 时的增加最为明显(调整后的 p 值 = 0.0461)。在 5 ATA 100%氧气条件下,与空气相比,大鼠大脑中的 FITC-二聚体水平显著增加(p 值 = 0.0327;效应大小 = 2.0)。在小鼠中,随着时间的推移,钆渗透到海马和额叶皮层的程度明显增加(调整后的 p 值结论):在啮齿类动物中,高压氧水平越高,生物BB越容易受到破坏,这首次表明高压氧与生物BB失调之间存在直接关系。我们建议在不同的潜水活动和使用高压氧舱的方案中考虑这一风险。另一方面,这项研究强调了高压氧在不同脑相关疾病中通过 BBB 向脑组织控制药物输送的潜在治疗用途。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exposure to hyperbaric O2 levels leads to blood-brain barrier breakdown in rodents.

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.

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来源期刊
Fluids and Barriers of the CNS
Fluids and Barriers of the CNS Neuroscience-Developmental Neuroscience
CiteScore
10.70
自引率
8.20%
发文量
94
审稿时长
14 weeks
期刊介绍: "Fluids and Barriers of the CNS" is a scholarly open access journal that specializes in the intricate world of the central nervous system's fluids and barriers, which are pivotal for the health and well-being of the human body. This journal is a peer-reviewed platform that welcomes research manuscripts exploring the full spectrum of CNS fluids and barriers, with a particular focus on their roles in both health and disease. At the heart of this journal's interest is the cerebrospinal fluid (CSF), a vital fluid that circulates within the brain and spinal cord, playing a multifaceted role in the normal functioning of the brain and in various neurological conditions. The journal delves into the composition, circulation, and absorption of CSF, as well as its relationship with the parenchymal interstitial fluid and the neurovascular unit at the blood-brain barrier (BBB).
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