title: Glucose and Intermediary Metabolism and Astrocyte-Neuron Interactions Following Neonatal Hypoxia-Ischemia in Rat.
abstract: Neonatal hypoxia-ischemia (HI) and the delayed injury cascade that follows involve excitotoxicity, oxidative stress and mitochondrial failure. The susceptibility to excitotoxicity of the neonatal brain may be related to the capacity of astrocytes for glutamate uptake. Furthermore, the neonatal brain is vulnerable to oxidative stress, and the pentose phosphate pathway (PPP) may be of particular importance for limiting this kind of injury. Also, in the neonatal brain, neurons depend upon de novo synthesis of neurotransmitters via pyruvate carboxylase in astrocytes to increase neurotransmitter pools during normal brain development. Several recent publications describing intermediary brain metabolism following neonatal HI have yielded interesting results: (1) Following HI there is a prolonged depression of mitochondrial metabolism in agreement with emerging evidence of mitochondria as vulnerable targets in the delayed injury cascade. (2) Astrocytes, like neurons, are metabolically impaired following HI, and the degree of astrocytic malfunction may be an indicator of the outcome following hypoxic and hypoxic-ischemic brain injury. (3) Glutamate transfer from neurons to astrocytes is not increased following neonatal HI, which may imply that astrocytes fail to upregulate glutamate uptake in response to the massive glutamate release during HI, thus contributing to excitotoxicity. (4) In the neonatal brain, the activity of the PPP is reduced following HI, which may add to the susceptibility of the neonatal brain to oxidative stress. The present review aims to discuss the metabolic temporal alterations observed in the neonatal brain following HI.
authors.affiliation: Department of Neuroscience, Norwegian University of Science and Technology (NTNU), 7489, Trondheim, Norway.|Department of Neurology, Bodø Hospital, Bodø, Norway.
authors.forename: Eva
authors.initials: E
authors.lastname: Brekke
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, NTNU, 7489, Trondheim, Norway.|Department of Pediatrics, St. Olavs Hospital, Trondheim University Hospital, 7006, Trondheim, Norway.
authors.forename: Hester Rijkje
authors.initials: HR
authors.lastname: Berger
authors.affiliation: Department of Circulation and Medical Imaging, NTNU, 7489, Trondheim, Norway.
authors.forename: Marius
authors.initials: M
authors.lastname: Widerøe
authors.affiliation: Department of Neuroscience, Norwegian University of Science and Technology (NTNU), 7489, Trondheim, Norway.|Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
authors.forename: Ursula
authors.initials: U
authors.lastname: Sonnewald
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, NTNU, 7489, Trondheim, Norway. tora.sund.morken@stolav.no.|Department of Ophthalmology, St. Olavs Hospital, Trondheim University Hospital, 7006, Trondheim, Norway. tora.sund.morken@stolav.no.
authors.forename: Tora Sund
authors.initials: TS
authors.lastname: Morken
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats
chemical_list: D005947:Glucose
keywords: 13C NMR; Astrocyte–neuron interactions; Glucose metabolism; Glutamate–glutamine cycle; Neonatal hypoxia–ischemia; Pentose-phosphate-pathway; Pyruvate carboxylation