Cellular alterations associated with perinatal asphyxia.
Asphyxia triggers a cascade of cellular biochemical events that lead to temporary alterations in cellular function and/or cell death. Tissue hypoxia and ischemia lead to depolarization of neuronal membranes, alteration in cellular ion homeostasis and changes in energy metabolism. The changes are accompanied by enhanced release and diminished re-uptake of neurotransmitters, including the excitatory amino acid glutamate. Abnormal accumulation of calcium in neurons is produced by several factors, including opening of voltage-sensitive calcium channels, activation of excitatory amino acid-mediated ion channels, diminished pumping of calcium out of neurons, and increased release of free calcium from the endoplasmic reticulum. Elevated intracellular calcium levels appear to kill cells by activation of proteases, lipases, protein kinase C, and generation of free radicals. These factors act synergistically over minutes to hours to produce cellular necrosis. Current research is directed at defining the relative contribution of these steps to cell death and to devising therapeutic strategies to salvage brain tissue.
Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
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Johnston
D000328:Adult; D000818:Animals; D001238:Asphyxia Neonatorum / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D011247:Pregnancy; D013569:Synapses / Q000502:physiology