Pharmacotherapeutical reduction of post-hypoxic-ischemic brain injury in the newborn.
Perinatal hypoxia-ischemia (PHI) is a major cause of morbidity and mortality. A substantial part of PHI-related brain damage occurs upon reperfusion and reoxygenation by the excess production of excitatory amino acids, free (pro)radicals and the release of cytokines, triggering programmed cell death. In this respect, several neuroprotective agents have been investigated in neonatal animal models, providing evidence for their usefulness in PHI. Several agents have been shown to be neuroprotective in neonatal animal hypoxia-ischemia models, but only a few agents have been used in clinical studies on term newborns. Although some general information will be provided with respect to focal hypoxia-ischemia and neuroprotective agents, this paper focuses on the investigated neuroprotective agents for global PHI and reperfusion brain injury in the newborn, categorized by their mode of action. Future experimental and clinical trials with promising neuroprotective agents need to be performed, including long-term follow-up to monitor long-term consequences. Moreover, well-designed combinations of neuroprotective agents with or without other neuroprotective strategies such as brain hypothermia should be given consideration for producing the most promising results in reducing post-hypoxic-ischemic reperfusion injury of the newborn brain.
Department of Neonatology, Wilhelmina Children's Hospital/University Medical Center, Utrecht, The Netherlands.
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Peeters
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van Bel
D017209:Apoptosis / Q000187:drug effects; D001927:Brain Diseases / Q000209:etiology* / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006133:Growth Substances / Q000627:therapeutic use; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000150:complications*; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D007502:Iron Chelating Agents / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016166:Free Radical Scavengers; D006133:Growth Substances; D018836:Inflammation Mediators; D007502:Iron Chelating Agents; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D014969:Xanthine Oxidase