The effects of therapeutic hypothermia on cerebral metabolism in neonates with hypoxic-ischemic encephalopathy: An in vivo 1H-MR spectroscopy study

Jessica L Wisnowski; Tai-Wei Wu; Aaron J Reitman; Claire McLean; Philippe Friedlich; Douglas Vanderbilt; Eugenia Ho; Marvin D Nelson; Ashok Panigrahy; Stefan Blüml

doi:10.1177/0271678X15607881

The effects of therapeutic hypothermia on cerebral metabolism in neonates with hypoxic-ischemic encephalopathy: An in vivo 1H-MR spectroscopy study

J Cereb Blood Flow Metab. 2016 Jun;36(6):1075-86. doi: 10.1177/0271678X15607881. Epub 2015 Oct 2.

Authors

Affiliations

¹ 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.
² Department of Pediatrics, Division of Neonatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan Department of Pediatrics, Division of Neonatology, Chang Gung University, Taoyuan, Taiwan.
³ 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.
⁴ 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.
⁵ 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.
⁶ Department of Radiology, Children's Hospital Los Angeles, Los Angeles, CA, USA.
⁷ 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.
⁸ Department of Radiology, Children's Hospital Los Angeles, Los Angeles, CA, USA Rudi Schulte Research Institute, Santa Barbara, CA, USA.

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.

Keywords: Energy metabolism; glutamate; hypothermia; neonatal ischemia; neuroprotection; neurotransmitters.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antioxidants / analysis
Brain / metabolism*
Homeostasis
Humans
Hypothermia, Induced*
Hypoxia-Ischemia, Brain / metabolism
Hypoxia-Ischemia, Brain / therapy*
Infant, Newborn
Magnetic Resonance Imaging
Neurotransmitter Agents / analysis
Rewarming

Substances

Antioxidants
Neurotransmitter Agents