HYPOxemia and HYPOthermia in foraging elephant seals: diving into physiological conundrums – HYPO2

The brain is highly vulnerable to hypoxia due to its high oxygen and energy demands to properly maintain functions. Various Human brain pathologies (i.e. stroke, traumatic brain injury, sleep apnea…) present hypoxia events with irreversible damages and no treatments. Traditional clinical human studies and animal experimental studies showed the limits to propose new therapeutical approaches. HYPO2 consortium believes that novel strategies need to be explored. Therefore, this consortium proposes to use a unique comparative physiological approach to understand how some mammals are able to cope with repeated severe hypoxic events. Among seals, Southern elephant seals (SES) (Mirounga leonina) are the most extreme divers, performing dives up to 2000 m while staying submerged for a staggering 120 min. SES have the exceptional ability to maintain the integrity of cognitive functions despite hypoxia during deep-long dives. This paradoxical situation is likely dependent of a fine balance between blood redistribution and hypothermia. Strikingly, seals have a conscious control over these physiological mechanisms when diving. SES hence provide a unique animal model to investigate physiological mechanisms of tolerance to hypoxia, and its potential cumulative effects. To gather a better understanding in adaptative physiological mechanisms, HYPO2 will address the following questions: 1) how circulatory physiology manages the challenge of oxygen deprivation in extreme environments; and 2) how the brain can maintain neuronal activity during apnea despite extremely low blood oxygen concentrations, and be protected from repeated hypoxic insults. These questions will be addressed in 3 different developmental ages (newly weaned pups n=21, juveniles -i.e. unexperienced seals- n=27, and adult seals n=18) to appreciate the role of experience and training in SES adaptations to hypoxia.
We will study SES in Kerguelen archipelago in free ranging and under experimental conditions (experimental respirometry chamber, translocation). In the work package (WP) 1 we will investigate how SES of different age groups reduce their metabolic rate at the organism level to avoid exceeding their age-respective ADL during increasing dive durations (apnea). In WP2, we will map seals’ cerebral activation and brain oxygenation coupling during the dives as a function of the development stage and the duration and depth of dives. In WP3, the effects of hypoxia/hypothermia on the metabolic capacities of seals will be studied at the cellular and molecular levels in their muscle and in their brain according to dive duration and age. The multidisciplinary team will provide a wide variety of measurements with recording of cerebral activity (EEG, NIRS), metabolism (cardiovascular recording with ECG) and muscle activities with fine-scale diving parameters related with recording of dive effort. The complementary expertise between partners will therefore ensure the success of this project.
This project is the first stepping stone to a future multidisciplinary program by aiming to study one of the most extreme diving seals. Build on this project, we will investigate how human practicing free diving can tolerate extreme hypoxic environment after training. We will finally translate the gathered knowledge to the bedside in the patients suffering of sleep apnea disorders with potential new therapeutical approaches.