Prolonged, moderate cerebral hypothermia initiated within a few hours after severe hypoxia-ischemia and continued until resolution of the acute phase of delayed cell death can reduce acute brain injury and improve long-term behavioral recovery in term infants and in adults after cardiac arrest. The specific mechanisms of hypothermic neuroprotection remain unclear, in part because hypothermia suppresses a broad range of potential injurious factors. This article examines proposed mechanisms in relation to the known window of opportunity for effective protection with hypothermia. Knowledge of the mechanisms of hypothermia will help guide the rational development of future combination treatments to augment neuroprotection with hypothermia and identify those most likely to benefit.
Keywords: Fetal sheep; Hypoxia-ischemia; Mechanisms; Neonatal encephalopathy; Neuroprotection; Newborn infant; Therapeutic hypothermia.
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