  Hyperbaric oxygen therapy (HBOT) proves vital in saving lives by elevating
the partial pressure of oxygen (pO2). However, HBOT may also have toxic
effects, including lung and retinal damage (peripheral HBOT toxicity), muscle
spasms and violent myoclonic convulsions (CNS HBOT toxicity), which may even
lead to death if left untreated. Despite the severity of the toxic effects of
HBOT, their mechanism is only poorly understood to date. This lack of
understanding the underlying mechanism hinders the development of new,
effective therapies and preventive strategies to supress HBOT toxicity. Herein,
we provide evidence that (1) increased pO2 increases the content of reactive
oxygen species (ROS) in tissues, which causes peripheral HBOT toxicity and
contributes to CNS toxicity by irreversibly altering cell receptors. Moreover,
(2) increased ROS concentration in brain lowers activity of glutamic
decarboxylase (GD), which lowers concentrations of inhibitory neurotransmitter
gamma-aminobutyric acid (GABA), thereby contributing to the onset of
HBOT-derived convulsions. At last, we provide long overlooked evidence that (3)
elevated ambient pressure directly inhibits GABA(A) and glycine receptors,
thereby leading to the rapid onset of HBOT-derived convulsions. We show that
only a combination of these three mechanisms (1 + 2 + 3) are needed to explain
most phenomena seen in HBOT toxicity (especially in CNS toxicity). Based on
these proposed intertwined mechanisms, we propose administering antioxidants
(lowering ROS concentrations), pyridoxine (restoring GD activity), and low
doses of sedatives/ anaesthetics (reversing inhibitory effects of pressure on
GABA(A) and glycine receptors) before routine hyperbaric oxygen therapies and
deep-sea diving to prevent the HBOT toxicity.
