Hypoxia-ischemia in the immature brain.
The immature brain has long been considered to be resistant to the damaging effects of hypoxia and hypoxia-ischemia (H/I). However, it is now appreciated that there are specific periods of increased vulnerability, which relate to the developmental stage at the time of the insult. Although much of our knowledge of the pathophysiology of cerebral H/I is based on extensive experimental studies in adult animal models, it is important to appreciate the major differences in the immature brain that impact on its response to, and recovery from, H/I. Normal maturation of the mammalian brain is characterized by periods of limitations in glucose transport capacity and increased use of alternative cerebral metabolic fuels such as lactate and ketone bodies, all of which are important during H/I and influence the development of energy failure. Cell death following H/I is mediated by glutamate excitotoxicity and oxidative stress, as well as other events that lead to delayed apoptotic death. The immature brain differs from the adult in its sensitivity to all of these processes. Finally, the ultimate outcome of H/I in the immature brain is determined by the impact on the ensuing cerebral maturation. A hypoxic-ischemic insult of insufficient severity to result in rapid cell death and infarction can lead to prolonged evolution of tissue damage.
Vannucci
Susan J
SJ
Department of Pediatrics, Columbia University, New York, NY 10032, USA. sv2020@columbia.edu
Hagberg
Henrik
H
D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D002648:Child; D004734:Energy Metabolism / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000503:physiopathology*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*
D009004:Monosaccharide Transport Proteins; D009498:Neurotoxins; D018698:Glutamic Acid