title: Altered astrocyte-neuronal interactions after hypoxia-ischemia in the neonatal brain in female and male rats.
abstract: OBJECTIVE
  Increased susceptibility to excitotoxicity of the neonatal brain after hypoxia-ischemia (HI) may be caused by limited capacity of astrocytes for glutamate uptake, and mitochondrial failure probably plays a key role in the delayed injury cascade. Male infants have poorer outcome than females after HI, possibly linked to differential intermediary metabolism.
  
  
  METHODS
  [1-(13)C]glucose and [1,2-(13)C]acetate were injected at zero, 6, and 48 hours after unilateral HI in 7-day-old rats. Intermediary metabolism was analyzed with magnetic resonance spectroscopy.
  
  
  RESULTS
  Mitochondrial metabolism was generally reduced in the ipsilateral hemisphere for ≤6 hours after HI, whereas contralaterally, it was reduced in neurons but not in astrocytes. Transfer of glutamate from neurons to astrocytes was increased in the contralateral, but not in the ipsilateral hemisphere at 0 hour, and reduced bilaterally at 6 hours after HI. The transfer of glutamine from astrocytes to glutamatergic neurons was unaltered in both hemispheres, whereas the transfer of glutamine to GABAergic neurons was increased ipsilaterally at 0 hour. Anaplerosis (astrocytes) was decreased, whereas partial pyruvate recycling (astrocytes) was increased directly after HI. Male pups had lower astrocytic mitochondrial metabolism than females immediately after HI, whereas that of females was reduced longer and encompassed both neurons and astrocytes.
  
  
  CONCLUSIONS
  The prolonged depression in mitochondrial metabolism indicates that mitochondria are vulnerable targets in the delayed injury after neonatal HI. The degree of astrocytic malfunction may be a valid indicator of outcome after hypoxic/HI brain injury and may be linked to the differential outcome in males and females.
authors: From the Department of Laboratory Medicine, Children's and Women's Health (T.S.M., A.-M.B.), Department of Neuroscience (E.B., A.H., U.S.), and Departments of Circulation and Medical Imaging (M.W.), Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Departments of Physical Medicine and Rehabilitation, St Olavs Hospital HF, Trondheim, Norway (T.S.M.); and Department of Medicine, Nordland Hospital Trust, Bodo, Norway (E.B.).
authors: Tora Sund
authors: TS
authors: Morken
authors: From the Department of Laboratory Medicine, Children's and Women's Health (T.S.M., A.-M.B.), Department of Neuroscience (E.B., A.H., U.S.), and Departments of Circulation and Medical Imaging (M.W.), Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Departments of Physical Medicine and Rehabilitation, St Olavs Hospital HF, Trondheim, Norway (T.S.M.); and Department of Medicine, Nordland Hospital Trust, Bodo, Norway (E.B.).
authors: Eva
authors: E
authors: Brekke
authors: From the Department of Laboratory Medicine, Children's and Women's Health (T.S.M., A.-M.B.), Department of Neuroscience (E.B., A.H., U.S.), and Departments of Circulation and Medical Imaging (M.W.), Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Departments of Physical Medicine and Rehabilitation, St Olavs Hospital HF, Trondheim, Norway (T.S.M.); and Department of Medicine, Nordland Hospital Trust, Bodo, Norway (E.B.).
authors: Asta
authors: A
authors: Håberg
authors: From the Department of Laboratory Medicine, Children's and Women's Health (T.S.M., A.-M.B.), Department of Neuroscience (E.B., A.H., U.S.), and Departments of Circulation and Medical Imaging (M.W.), Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Departments of Physical Medicine and Rehabilitation, St Olavs Hospital HF, Trondheim, Norway (T.S.M.); and Department of Medicine, Nordland Hospital Trust, Bodo, Norway (E.B.).
authors: Marius
authors: M
authors: Widerøe
authors: From the Department of Laboratory Medicine, Children's and Women's Health (T.S.M., A.-M.B.), Department of Neuroscience (E.B., A.H., U.S.), and Departments of Circulation and Medical Imaging (M.W.), Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Departments of Physical Medicine and Rehabilitation, St Olavs Hospital HF, Trondheim, Norway (T.S.M.); and Department of Medicine, Nordland Hospital Trust, Bodo, Norway (E.B.).
authors: Ann-Mari
authors: AM
authors: Brubakk
authors: From the Department of Laboratory Medicine, Children's and Women's Health (T.S.M., A.-M.B.), Department of Neuroscience (E.B., A.H., U.S.), and Departments of Circulation and Medical Imaging (M.W.), Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Departments of Physical Medicine and Rehabilitation, St Olavs Hospital HF, Trondheim, Norway (T.S.M.); and Department of Medicine, Nordland Hospital Trust, Bodo, Norway (E.B.). ursula.sonnewald@ntnu.no.
authors: Ursula
authors: U
authors: Sonnewald
mesh_terms: D000085:Acetates / Q000737:chemistry; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000254:growth & development* / Q000378:metabolism; D005260:Female; D059330:GABAergic Neurons / Q000378:metabolism; D005947:Glucose / Q000737:chemistry; D006019:Glycolysis; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000085:Acetates; D005947:Glucose
keywords: cerebral hypoxia ischemia; magnetic resonance spectroscopy; neuron glia; rats