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Metabolic Alterations in Developing Brain After Injury: Knowns and Unknowns

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Abstract

Brain development is a highly orchestrated complex process. The developing brain utilizes many substrates including glucose, ketone bodies, lactate, fatty acids and amino acids for energy, cell division and the biosynthesis of nucleotides, proteins and lipids. Metabolism is crucial to provide energy for all cellular processes required for brain development and function including ATP formation, synaptogenesis, synthesis, release and uptake of neurotransmitters, maintaining ionic gradients and redox status, and myelination. The rapidly growing population of infants and children with neurodevelopmental and cognitive impairments and life-long disability resulting from developmental brain injury is a significant public health concern. Brain injury in infants and children can have devastating effects because the injury is superimposed on the high metabolic demands of the developing brain. Acute injury in the pediatric brain can derail, halt or lead to dysregulation of the complex and highly regulated normal developmental processes. This paper provides a brief review of metabolism in developing brain and alterations found clinically and in animal models of developmental brain injury. The metabolic changes observed in three major categories of injury that can result in life-long cognitive and neurological disabilities, including neonatal hypoxia–ischemia, pediatric traumatic brain injury, and brain injury secondary to prematurity are reviewed.

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Abbreviations

BBB:

Blood–brain barrier

BHB:

β-Hydroxybutyrate

BHBdehase:

β-Hydroxybutyrate dehydrogenase

CCI:

Controlled cortical impact traumatic brain injury

Cho or tCho:

Total choline

Cr or tCr:

Total creatine

Gln:

Glutamine

Glu:

Glutamate

Glx:

Glutamate and glutamine

GPC:

Glycerophosphocholine

HI:

Hypoxia–ischemia

HIE:

Hypoxic–ischemic encephalopathy

1H-MRS:

Proton magnetic resonance spectroscopy

Lac:

Lactate

MRI:

Magnetic resonance imaging

MRS:

Magnetic resonance spectroscopy

NAA:

N-acetylaspartate

PC:

Pyruvate carboxylase

PDH:

Pyruvate dehydrogenase

PND:

Postnatal day

PPP:

Pentose phosphate pathway

TBI:

Traumatic brain injury

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Acknowledgments

Supported in part by NIH Grants 5P01 HD016596 (M.C.M.) and K08 NS 069815 (S.S.).

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None.

Human and animal rights

This article does not contain any studies with human participants performed by any of the authors. All animal studies by the authors that are cited in this study were approved by IACUC and performed in compliance with all NIH guidelines for animal research.

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Authors and Affiliations

  1. Department of Pediatrics and Program in Neuroscience, University of Maryland School of Medicine, 655 W. Baltimore St., Room 13-019, Baltimore, MD, 21201, USA

    Mary C. McKenna

  2. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Susanna Scafidi & Courtney L. Robertson

  3. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Courtney L. Robertson

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  1. Mary C. McKenna
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  2. Susanna Scafidi
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  3. Courtney L. Robertson
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Correspondence to Mary C. McKenna.

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Special Issue: In Honor of Dr. Gerald Dienel.

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McKenna, M.C., Scafidi, S. & Robertson, C.L. Metabolic Alterations in Developing Brain After Injury: Knowns and Unknowns. Neurochem Res 40, 2527–2543 (2015). https://doi.org/10.1007/s11064-015-1600-7

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