Abstract
Unilateral hypoxia-ischemia (HI) was induced in C57/BL6 male mice on postnatal day (P) 5, 9, 21 and 60, corresponding developmentally to premature, term, juvenile and adult human brains, respectively. HI duration was adjusted to obtain a similar extent of brain injury at all ages. Apoptotic mechanisms (nuclear translocation of apoptosis-inducing factor, cytochrome c release and caspase-3 activation) were several-fold more pronounced in immature than in juvenile and adult brains. Necrosis-related calpain activation was similar at all ages. The CA1 subfield shifted from apoptosis-related neuronal death at P5 and P9 to necrosis-related calpain activation at P21 and P60. Oxidative stress (nitrotyrosine formation) was also similar at all ages. Autophagy, as judged by the autophagosome-related marker LC-3 II, was more pronounced in adult brains. To our knowledge, this is the first report demonstrating developmental regulation of AIF-mediated cell death as well as involvement of autophagy in a model of brain injury.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aging / physiology*
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Animals
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Apoptosis / physiology*
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Apoptosis Inducing Factor
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Autophagy / physiology
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Brain Injuries / metabolism
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Brain Injuries / pathology
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Brain Injuries / physiopathology
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Calpain / metabolism
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Caspase 3
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Caspases / metabolism
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Cell Death / physiology
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Cytochromes c / metabolism
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Disease Models, Animal
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Flavoproteins / metabolism
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Hypoxia-Ischemia, Brain / metabolism
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Hypoxia-Ischemia, Brain / pathology
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Hypoxia-Ischemia, Brain / physiopathology*
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Male
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Microtubule-Associated Proteins / metabolism
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Mitochondria / metabolism
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Necrosis / metabolism
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Neurons / metabolism
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Neurons / physiology
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Protein Transport
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Tyrosine / analogs & derivatives
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Tyrosine / metabolism
Substances
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Apoptosis Inducing Factor
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Flavoproteins
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Membrane Proteins
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Microtubule-Associated Proteins
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AIFM1 protein, mouse
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3-nitrotyrosine
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Tyrosine
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Cytochromes c
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CASP3 protein, human
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Calpain
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Casp3 protein, mouse
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Caspase 3
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Caspases