title: Mechanisms of hypoxic neurodegeneration in the developing brain.
abstract: Asphyxia and other insults to the developing brain are responsible for several human neurodevelopmental disorders. The pattern of neonatal brain injury differs from that seen in the adult nervous system, and there are wide differences in regional vulnerability. Recent evidence suggests that two events that contribute to this pattern of selective vulnerability are developmental changes in excitatory glutamate-containing neurotransmitter circuits and the propensity for immature neurons to die by apoptosis rather than necrosis. Developmental up-regulation of NMDA receptors with enhanced function and increased expression of caspase-3 at critical periods in development are linked to these mechanisms. Although these molecular changes enhance the developing brain's capacity for plasticity by helping to prune redundant synapses and neurons, they can become "Achilles heels" in the face of a brain energy crisis.
authors.affiliation: Department of Neurology and Pediatrics and Kenedy Kreger Research Institute, John Hopkins University School of Medicine, Baltimore, Maryland 21205,USA. Johnston@kennedykrieger.org
authors.forename: Michael V
authors.initials: MV
authors.lastname: Johnston
authors.forename: Wako
authors.initials: W
authors.lastname: Nakajima
authors.forename: Henrik
authors.initials: H
authors.lastname: Hagberg
mesh_terms: D017209:Apoptosis; D001237:Asphyxia / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D018846:Excitatory Amino Acids / Q000009:adverse effects; D006801:Humans; D002534:Hypoxia, Brain / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018846:Excitatory Amino Acids; D016194:Receptors, N-Methyl-D-Aspartate; D020169:Caspases