Abstract
Multiple, biochemical cascades contribute to the pathogenesis of neonatal hypoxic-ischemic brain injury. This article summarizes experimental evidence that supports the role of excitatory amino acids, calcium, free radicals, nitric oxide, proinflammatory cytokines, and bioactive lipids. Specific vulnerabilities that distinguish the response of the immature brain from that of the mature brain are highlighted. These include increased susceptibility to excitotoxicity and free radical injury, greater tendency to apoptotic death, and heightened vulnerability of developing oligodendrocytes. Available supportive evidence from human studies is also included. Implications for clinical neuroprotective strategies are discussed.
Publication types
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Animals
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Apoptosis / physiology
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Birth Injuries / etiology*
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Birth Injuries / metabolism*
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Birth Injuries / prevention & control
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Brain Chemistry
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Calcium / metabolism
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Cytokines / metabolism
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Disease Models, Animal
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Excitatory Amino Acids / metabolism
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Free Radicals / metabolism
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Humans
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Hypothermia, Induced
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Hypoxia-Ischemia, Brain / congenital*
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Hypoxia-Ischemia, Brain / metabolism*
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Hypoxia-Ischemia, Brain / prevention & control
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Infant, Newborn
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Lipid Peroxidation / physiology
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Neuroprotective Agents / therapeutic use
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Nitric Oxide / metabolism
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Oligodendroglia / physiology
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Risk Factors
Substances
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Cytokines
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Excitatory Amino Acids
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Free Radicals
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Neuroprotective Agents
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Nitric Oxide
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Calcium