title: Mitochondrial impairment in the developing brain after hypoxia-ischemia.
abstract: The pattern of cell death in the immature brain differs from that seen in the adult CNS. During normal development, more than half of the neurons are removed through apoptosis, and mediators like caspase-3 are highly upregulated. The contribution of apoptotic mechanisms in cell death appears also to be substantial in the developing brain, with a marked activation of downstream caspases and signs of DNA fragmentation. Mitochondria are important regulators of cell death through their role in energy metabolism and calcium homeostasis, and their ability to release apoptogenic proteins and to produce reactive oxygen species. We find that secondary brain injury is preceded by impairment of mitochondrial respiration, signs of membrane permeability transition, intramitochondrial accumulation of calcium, changes in the Bcl-2 family proteins, release of proapoptotic proteins (cytochrome C, apoptosis inducing factor) and downstream activation of caspase-9 and caspase-3 after hypoxia-ischemia. These data support the involvement of mitochondria-related mechanisms in perinatal brain injury.
authors.affiliation: Perinatal Center, Department for the Health of Women and Children, Sahlgrenska Academy, East Hospital, 416 85. henrik.hagberg@obgyn.gu.se
authors.forename: Henrik
authors.initials: H
authors.lastname: Hagberg
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001238:Asphyxia Neonatorum / Q000196:embryology / Q000378:metabolism; D001921:Brain / Q000196:embryology / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000196:embryology* / Q000378:metabolism*; D007231:Infant, Newborn; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D028361:Mitochondrial Diseases / Q000196:embryology* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism* / Q000473:pathology
chemical_list: D024101:Mitochondrial Proteins; D020169:Caspases