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.

Dopamine-dependent biphasic behaviour under 'deep diving' conditions in Caenorhabditis elegans.

Underwater divers are susceptible to neurological risks due to their exposure to increased pressure. Absorption of elevated partial pressure of inert gases such as helium and nitrogen may lead to nitrogen narcosis. Although the symptoms of nitrogen narcosis are known, the molecular mechanisms underlying these symptoms have not been elucidated. Here, we examined the behaviour of the soil nematode Caenorhabditis elegans under scuba diving conditions. We analysed wild-type animals and mutants in the dopamine pathway under hyperbaric conditions, using several gas compositions and under varying pressure levels. We found that the animals changed their speed on a flat bacterial surface in response to pressure in a biphasic mode that depended on dopamine. Dopamine-deficient cat-2 mutant animals did not exhibit a biphasic response in high pressure, while the extracellular accumulation of dopamine in dat-1 mutant animals mildly influenced this response. Our data demonstrate that in C. elegans, similarly to mammalian systems, dopamine signalling is involved in the response to high pressure. This study establishes C. elegans as a powerful system to elucidate the molecular mechanisms that underly nitrogen toxicity in response to high pressure.