Hypoxic-ischemic brain injury and neuroprotection in the newborn infant

Recent clinical trials have confirmed that in term infants with moderate-to-severe hypoxic-ischemic encephalopathy, death and severe developmental disability can be reduced by early treatment with hypothermia. However, meta-analysis of these trials has confirmed that two-thirds of the survivors remain seriously impaired. The search for new neuroprotective interventions has therefore continued. Extensive research has identified the important biochemical pathways that result in neuronal loss, and the subsequent repair and regeneration processes. The most promising neuroprotective agents that limit the former, and promote the latter, are being tested in animal models of hypoxic-ischemic brain injury and are awaiting clinical trials. It is likely that a 'cocktail' of agents, affecting a number of pathways, will ultimately prove to be the most effective intervention. The latest additions to a long list of proposed substances are various stem cells that promote neurogenesis by releasing trophic substances into the injured brain. Future clinical trials are likely to employ early biomarkers, of which MRI and proton spectroscopy are probably the most predictive of long-term neurodevelopmental outcome. In conclusion, the exponential increase in knowledge in this field can be expected to provide many more neuroprotective agents within the next decade.