title: The effects of therapeutic hypothermia on cerebral metabolism in neonates with hypoxic-ischemic encephalopathy: An in vivo 1H-MR spectroscopy study.
abstract: Therapeutic hypothermia has emerged as the first empirically supported therapy for neuroprotection in neonates with hypoxic-ischemic encephalopathy (HIE). We used magnetic resonance spectroscopy ((1)H-MRS) to characterize the effects of hypothermia on energy metabolites, neurotransmitters, and antioxidants. Thirty-one neonates with HIE were studied during hypothermia and after rewarming. Metabolite concentrations (mmol/kg) were determined from the thalamus, basal ganglia, cortical grey matter, and cerebral white matter. In the thalamus, phosphocreatine concentrations were increased by 20% during hypothermia when compared to after rewarming (3.49 ± 0.88 vs. 2.90 ± 0.65, p < 0.001) while free creatine concentrations were reduced to a similar degree (3.00 ± 0.50 vs. 3.74 ± 0.85, p < 0.001). Glutamate (5.33 ± 0.82 vs. 6.32 ± 1.12, p < 0.001), aspartate (3.39 ± 0.66 vs. 3.87 ± 1.19, p < 0.05), and GABA (0.92 ± 0.36 vs. 1.19 ± 0.41, p < 0.05) were also reduced, while taurine (1.39 ± 0.52 vs. 0.79 ± 0.61, p < 0.001) and glutathione (2.23 ± 0.41 vs. 2.09 ± 0.33, p < 0.05) were increased. Similar patterns were observed in other brain regions. These findings support that hypothermia improves energy homeostasis by decreasing the availability of excitatory neurotransmitters, and thereby, cellular energy demand.
authors.affiliation: Department of Radiology, Children's Hospital Los Angeles, Los Angeles, CA, USA Brain and Creativity Institute, University of Southern California, Los Angeles, CA, USA Department of Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA Rudi Schulte Research Institute, Santa Barbara, CA, USA jwisnowski@chla.usc.edu.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Wisnowski
authors.affiliation: Department of Pediatrics, Division of Neonatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan Department of Pediatrics, Division of Neonatology, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Tai-Wei
authors.initials: TW
authors.lastname: Wu
authors.affiliation: Center for Fetal and Neonatal Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA Department of Pediatrics, Division of Neonatal Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Reitman
authors.affiliation: Center for Fetal and Neonatal Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA Department of Pediatrics, Division of Neonatal Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: McLean
authors.affiliation: Center for Fetal and Neonatal Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA Department of Pediatrics, Division of Neonatal Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Philippe
authors.initials: P
authors.lastname: Friedlich
authors.affiliation: Center for Fetal and Neonatal Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA Department of Pediatrics, Developmental-Behavioral Pediatrics, University of Southern California, Los Angeles, CA, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Vanderbilt
authors.affiliation: Center for Fetal and Neonatal Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA Department of Pediatrics, Division of Child Neurology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Ho
authors.affiliation: Department of Radiology, Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: Marvin D
authors.initials: MD
authors.lastname: Nelson
authors.affiliation: Department of Radiology, Children's Hospital Los Angeles, Los Angeles, CA, USA Brain and Creativity Institute, University of Southern California, Los Angeles, CA, USA Department of Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.
authors.forename: Ashok
authors.initials: A
authors.lastname: Panigrahy
authors.affiliation: Department of Radiology, Children's Hospital Los Angeles, Los Angeles, CA, USA Rudi Schulte Research Institute, Santa Barbara, CA, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Blüml
mesh_terms: D000975:Antioxidants / Q000032:analysis; D001921:Brain / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000628:therapy*; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D018377:Neurotransmitter Agents / Q000032:analysis; D017694:Rewarming
chemical_list: D000975:Antioxidants; D018377:Neurotransmitter Agents
keywords: Energy metabolism; glutamate; hypothermia; neonatal ischemia; neuroprotection; neurotransmitters