Despite comprising only approximately 2% of total body weight, the brain accounts for around 20% of total body oxygen consumption and 25% of total glucose utilisation at rest. This extraordinarily high metabolic demand reflects the energy cost of maintaining the ionic gradients across neuronal membranes, generating and propagating action potentials, and sustaining the vast number of synaptic transmissions that underpin consciousness, cognition, and autonomic function.

The brain’s metabolic machinery is almost entirely dependent on two substrates: oxygen and glucose. Unlike skeletal muscle or the liver, the brain has negligible glycogen stores and cannot synthesise glucose. It relies on continuous delivery of glucose from the systemic circulation, making it uniquely vulnerable to hypoglycaemia. Even brief periods of profound hypoglycaemia — lasting minutes — cause irreversible neuronal death in vulnerable areas such as the hippocampus and cerebral cortex.

Glucose is metabolised to ATP primarily through aerobic glycolysis and oxidative phosphorylation. In the absence of oxygen, anaerobic metabolism can sustain neuronal function for only a very short time — the brain tolerates complete cessation of blood flow for approximately 4–5 minutes before irreversible injury begins. This time window is the basis for the urgency of CPR in cardiac arrest and the imperative to restore perfusion pressure as rapidly as possible in any condition causing cerebral ischaemia.