Cooling the brain is a therapeutic strategy to protect it from stress. The long-held belief is that cooling the brain reduces its activity — and thus its need for oxygen — thereby tilting a favourable balance of oxygen supply and demand. However, recent data from our lab challenges this paradigm. We have shown that brain blood flow is reduced by whole-body cooling, and this dramatically impairs oxygen supply to the brain. Therefore, it is important to know exactly how much the brain’s activity is reduced so that we can determine whether the balance of oxygen supply and demand is improved or further disrupted. Surprisingly, this is unknown in the human brain. Our objective is determine how the brain’s oxygen supply and demand is affected by cooling and heating, and how this impacts its resilience to stress. We will heat and cool healthy human subjects and expose them to low oxygen, whilst measuring markers of brain stress. We will then collect the same markers of brain stress in patients with brain injury before, during and after therapeutic cooling. Together, these studies will expose how temperature affects the brain’s resilience to stress and provide rationale for how best to harness the cold to protect the brain.