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Molecular Neurobiology

, Volume 56, Issue 4, pp 2908–2921 | Cite as

Chronic Dysregulation of Cortical and Subcortical Metabolism After Experimental Traumatic Brain Injury

  • Jennifer L. McGuireEmail author
  • Erica A. K. DePasquale
  • Miki Watanabe
  • Fatima Anwar
  • Laura B. Ngwenya
  • Gowtham Atluri
  • Lindsey E. Romick-Rosendale
  • Robert E. McCullumsmith
  • Nathan K. Evanson
Article

Abstract

Traumatic brain injury (TBI) is a leading cause of death and long-term disability worldwide. Although chronic disability is common after TBI, effective treatments remain elusive and chronic TBI pathophysiology is not well understood. Early after TBI, brain metabolism is disrupted due to unregulated ion release, mitochondrial damage, and interruption of molecular trafficking. This metabolic disruption causes at least part of the TBI pathology. However, it is not clear how persistent or pervasive metabolic injury is at later stages of injury. Using untargeted 1H-NMR metabolomics, we examined ex vivo hippocampus, striatum, thalamus, frontal cortex, and brainstem tissue in a rat lateral fluid percussion model of chronic brain injury. We found altered tissue concentrations of metabolites in the hippocampus and thalamus consistent with dysregulation of energy metabolism and excitatory neurotransmission. Furthermore, differential correlation analysis provided additional evidence of metabolic dysregulation, most notably in brainstem and frontal cortex, suggesting that metabolic consequences of injury are persistent and widespread. Interestingly, the patterns of network changes were region-specific. The individual metabolic signatures after injury in different structures of the brain at rest may reflect different compensatory mechanisms engaged to meet variable metabolic demands across brain regions.

Keywords

NMR metabolomics Chronic TBI Lateral fluid percussion Network structure Correlations-based analysis 

Notes

Funding Information

These studies received financial support from Cincinnati Children’s Hospital Medical Center as a Shared Facilities Discovery Award to NKE and JLM.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jennifer L. McGuire
    • 1
    Email author
  • Erica A. K. DePasquale
    • 2
  • Miki Watanabe
    • 3
  • Fatima Anwar
    • 1
  • Laura B. Ngwenya
    • 1
    • 4
  • Gowtham Atluri
    • 2
    • 5
  • Lindsey E. Romick-Rosendale
    • 3
  • Robert E. McCullumsmith
    • 6
  • Nathan K. Evanson
    • 7
    • 8
  1. 1.Department of NeurosurgeryUniversity of CincinnatiCincinnatiUSA
  2. 2.Graduate Program in Biomedical InformaticsUniversity of CincinnatiCincinnatiUSA
  3. 3.Division of PathologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  4. 4.Department of Neurology and Rehabilitation MedicineUniversity of CincinnatiCincinnatiUSA
  5. 5.Department of Electrical Engineering and Computer ScienceUniversity of CincinnatiCincinnatiUSA
  6. 6.Department of Psychiatry and Behavioral NeuroscienceUniversity of CincinnatiCincinnatiUSA
  7. 7.Department of PediatricsUniversity of CincinnatiCincinnatiUSA
  8. 8.Division of Pediatric Rehabilitation MedicineCincinnati Children’s Hospital Medical CenterCincinnatiUSA

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