Abstract
One’s ability to survive and thrive in diverse environments relies on both behavioural and physiological responses, which act together to maintain a suitable internal environment. Physiological responses occur automatically in proportion to the degree of strain imparted by the stimulus, whereas behavioural responses are learned and require adequate cognitive capacity to perceive, interpret and respond to threatening situations. As it is central to both physiological and behavioural responses, understanding how the brain tolerates various environmental stressors is essential in predicting how well an individual as a whole will tolerate these stressors.
Study 1 investigated how acute and chronic hypoxia affected cerebral haemodynamics during cold and heat stress. Healthy males were passively cooled by 1 °C and heated by 1.5 °C core temperature at sea level and again after 16 days at high altitude (4330 m). Core cooling reduced global cerebral blood flow, as assessed by duplex ultrasound, by 20-30%, and cerebral oxygen delivery by 12-19% at sea level and high altitude, whereas heat stress did not reliably reduce cerebral blood flow or oxygen delivery. Acclimatisation to 4330 m fully restored arterial oxygen content, but concurrent cold stress reduced cerebral blood flow and thereby cerebral oxygen delivery. Decreases in cerebral blood flow appeared to be driven primarily by cold-induced hypocapnia secondary to hyperventilation. Despite decreases in cerebral oxygen delivery by up to 19%, gross indices of cognition were unaffected. In summary, chronic hypoxia renders the brain susceptible to large reductions in oxygen delivery with concurrent cold stress, however, these impairments appear to be well tolerated short-term.
Study 2 investigated the temporal changes in cerebral blood flow under four different modes of incremental heating, as well as the role of heating in elevating intracranial pressure. Healthy males and females were heated to volitional thermal tolerance via: (1) passive hot water immersion, (2) passive hot, humid air exposure, (3) cycling in the heat, and (4) cycling in the heat with the prevention of heat-induced hypocapnia. The cerebral blood flow response to incremental heat strain was dependent on the mode of heating, decreasing by 30% when passively exposed to hot, humid air, while remaining unchanged or increasing with hot water immersion and both exercise conditions. Despite a consistent blunting of cerebrovascular reactivity to hypocapnia, cerebral blood flow at thermal tolerance appeared to be largely influenced by the magnitude of hypocapnia that developed as a consequence of heat-induced hyperventilation. Thermal tolerance was equally superior in the two passive heating conditions despite a 25% difference in cerebral blood flow, and preventing hypocapnia during cycling increased cerebral blood flow by 25% but had no influence on exercising tolerance. Perception of thermal discomfort and thermal behaviour, i.e., volitional tolerance, did not appear to be affected by cerebral blood flow. Intracranial pressure, as estimated by optic nerve sheath diameter, was increased universally by 18% at volitional thermal tolerance in all modes of heating. In summary, passive hot, humid air exposure poses the greatest challenge to the brain under moderate- to severe- heating due to lower blood flow but similarly increased intracranial pressure.
Instead of further interrogating the cerebrovascular responses to environmental stress, study 3 focussed on the mechanisms that drive hyperventilation – which based on studies 1 and 2 – largely explain the cerebral blood flow responses to both cold and heat stress. The carotid body was targeted because the ventilatory response to acute and chronic hypoxia was profoundly augmented under thermal stress in study 1. Carotid body tonic activity was assessed by transient hyperoxia, and its sensitivity by isocapnic hypoxia under both graded heating and cooling. Carotid body tonic activity was increased in a dose-dependent manner with graded heating, reaching a maximum that was 175% above baseline at +2 °C core temperature. Core cooling increased carotid body activity by up to 250% under mild cooling, i.e., -1 °C core temperature. Despite hypocapnic restraint secondary to heat-induced hyperventilation, carotid body sensitivity to hypoxia was augmented by up to 115% with heat stress. Carotid body sensitivity was minimally increased (~30%) by core cooling under much less hypocapnic restraint. In summary, heat stress increases both the carotid body tonic activity and its sensitivity, providing two interrelated mechanisms by which the carotid body contributes to heat-induced hyperventilation.
This collection of studies exposed the complex interactions involved in maintaining brain allostasis under severe environmental stress and provides evidence that: 1) the balance of arterial carbon dioxide pressure and oxygen content largely dictate the cerebral blood flow response under cold, heat and hypoxic stress - alone and in combination - but cerebrovascular sensitivities to both gases are selectively altered to protect cerebral oxygen delivery; 2) transient elevations in intracranial pressure occur in healthy heated humans and may drive thermal behaviour; and, 3) the carotid body likely plays a dominant role in driving heat-induced hyperventilation. Lastly, it appears that alongside the diverse autonomous responses that act collectively to protect the brain, cognition and perception are still well preserved even when the brain’s internal environment is temporarily compromised under the severest of environments.