Keeping a cool head, post-hypoxic hypothermia--an old idea revisited.

Hypoxia-ischaemia produces permanent brain damage by processes that continue for many hours after reoxygenation/reperfusion. This provides a window of opportunity for therapy aimed at preventing further loss of brain cells. Reducing brain temperature by 2-6 degrees C for 3-72 h after reoxygenation/reperfusion has been shown to reduce brain damage by 25-80% in controlled trials with six different neonatal animal models of hypoxia-ischaemia. No adverse effects from mild hypothermia have been documented. The mechanisms of protection are unknown but may include a reduction in extracellular excitotoxic amino acids, reduced nitric oxide synthesis and inhibition of apoptosis. Mild hypothermia is currently the most promising clinically feasible neural rescue therapy for full-term infants at risk of developing hypoxic-ischaemic encephalopathy, but clinical use must be restricted to approved trial protocols.