Combined melatonin and bright light therapy mitigate central nervous system oxygen toxicity after day-to-night transition

The greatest risk involved in diving with closed-circuit oxygen rebreather is the development of CNS-oxygen toxicity (CNS-OT), which can be fatal underwater. We previously found in the diurnal model fat sand rat (<i>Psammomys obesus</i>) that night activity is an additional risk factor for CNS-OT. Here, we evaluated protective means which improve the resistance of sand rat to CNS-OT following indoor housing (which cause a shift to nocturnal activity). Five groups of animals were used: one outdoor, day active group (D), and four night active groups composed of (1) indoors group with no treatment (I), (2) indoor group treated with bright light therapy and melatonin (Indoors + light + Mel, ILM), (3) indoor group treated with melatonin only (Indoors + Mel, IM), and (4) indoor group treated only with light therapy (Indoors + Light + IL). The indoors groups underwent 3 weeks of indoor housing. On completion of this term, 6-Sulfatoxymelatonin (6-SMT) levels in urine were determined over a period of 24 h. Animals were then exposed to hyperbaric oxygen (HBO), and we timed the latency to CNS-OT followed by measuring neuronal nitric oxide synthase (nNOS) and nitrotyrosine (NT) levels in the hippocampus. The results indicate that indoor housing (nocturnal activity) shortened the latency to CNS-OT compared to outdoors, diurnal activity. The combined treatment contributed to the elongation of the latency to CNS-OT, which was similar to that of the diurnal group. These changes were accompanied by a significant decrease in hippocampal nNOS and NT levels following the combined treatment compared with the nocturnal group with no treatment. We conclude that the combined treatment may provide protection against CNS-OT in night active sand rats. This protection may partly be attributed to a reduction in hippocampal nNOS and NT levels. Our results indicate that vulnerability to CNS-OT is increased by day-night transition activity and provide new potential treatment for CNS-OT.