title: No improvement of neuronal metabolism in the reperfusion phase with melatonin treatment after hypoxic-ischemic brain injury in the neonatal rat.
abstract: Mitochondrial impairment is a key feature underlying neonatal hypoxic-ischemic (HI) brain injury and melatonin is potentially neuroprotective through its effects on mitochondria. In this study, we have used (1) H and (13) C NMR spectroscopy after injection of [1-(13) C]glucose and [1,2-(13) C]acetate to examine neuronal and astrocytic metabolism in the early reperfusion phase after unilateral HI brain injury in 7-day-old rat pups, exploring the effects of HI on mitochondrial function and the potential protective effects of melatonin on brain metabolism. One hour after hypoxia-ischemia, astrocytic metabolism was recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was clearly impaired. Pyruvate carboxylation was also lower in both hemispheres after HI. The transfer of glutamate from neurons to astrocytes was higher whereas the transfer of glutamine from astrocytes to neurons was lower 1 h after HI in the contralateral hemisphere. Neuronal metabolism was equally affected in pups treated with melatonin (10 mg/kg) immediately after HI as in vehicle treated pups indicating that the given dose of melatonin was not capable of protecting the neuronal mitochondria in this early phase after HI brain injury. However, any beneficial effects of melatonin might have been masked by modulatory effects of the solvent dimethyl sulfoxide on cerebral metabolism. Neuronal and astrocytic metabolism was examined by (13) C and (1) H NMR spectroscopy in the early reperfusion phase after unilateral hypoxic-ischemic brain injury and melatonin treatment in neonatal rats. One hour after hypoxia-ischemia astrocytic mitochondrial metabolism had recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was impaired. Melatonin treatment did not show a protective effect on neuronal metabolism.
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Hester R
authors.initials: HR
authors.lastname: Berger
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.|Department of Ophthalmology, Trondheim University Hospital, Trondheim, Norway.
authors.forename: Tora Sund
authors.initials: TS
authors.lastname: Morken
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Riyas
authors.initials: R
authors.lastname: Vettukattil
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Ann-Mari
authors.initials: AM
authors.lastname: Brubakk
authors.affiliation: Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.|Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ursula
authors.initials: U
authors.lastname: Sonnewald
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Marius
authors.initials: M
authors.lastname: Widerøe
mesh_terms: D000085:Acetates / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000627:therapeutic use*; D001253:Astrocytes / Q000378:metabolism; D001930:Brain Injuries / Q000209:etiology* / Q000473:pathology / Q000628:therapy*; D002545:Brain Ischemia / Q000150:complications*; D004195:Disease Models, Animal; D005260:Female; D007839:Functional Laterality / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D007554:Isotopes / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008550:Melatonin / Q000627:therapeutic use*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011247:Pregnancy; D011766:Pyruvate Carboxylase / Q000378:metabolism; D051381:Rats; D015424:Reperfusion
chemical_list: D000085:Acetates; D000975:Antioxidants; D007554:Isotopes; D011766:Pyruvate Carboxylase; D005947:Glucose; D008550:Melatonin
keywords: 13C-NMR spectroscopy; astrocyte; cerebral; mitochondria