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Metabolic Crisis After Traumatic Brain Injury is Associated with a Novel Microdialysis Proteome

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Abstract

Background

To examine if the metabolic distress after traumatic brain injury (TBI) is associated with a unique proteome.

Methods

Patients with severe TBI prospectively underwent cerebral microdialysis for the initial 96 h after injury. Hourly sampling of metabolism was performed and patients were categorized as having normal or abnormal metabolism as evidenced by the lactate/pyruvate ratio (LPR) threshold of 40. The microdialysate was frozen for proteomic batch processing retrospectively. We employed two different routes of proteomic techniques utilizing mass spectrometry (MS) and categorized as diagnostic and biomarker identification approaches. The diagnostic approach was aimed at finding a signature of MS peaks which can differentiate these two groups. We did this by enriching for intact peptides followed by MALDI-MS analysis. For the biomarker identification approach, we applied classical bottom-up (trypsin digestion followed by LC-MS/MS) proteomic methodologies.

Results

Five patients were studied, 3 of whom had abnormal metabolism and 2 who had normal metabolism. By comparison, the abnormal group had higher LPR (1609 ± 3691 vs. 15.5 ± 6.8, P < 0.001), higher glutamate (157 ± 84 vs. 1.8 ± 1.4 μM, P < 0.001), and lower glucose (0.27 ± 0.35 vs. 1.8 ± 1.1 mmol/l, P < 0.001). The abnormal group demonstrated 13 unique proteins as compared with the normal group in the microdialysate. These proteins consisted of cytoarchitectural proteins, as well as blood breakdown proteins, and a few mitochondrial proteins. A unique as yet to be characterized peptide was found at m/z (mass/charge) 4733.5, which may represent a novel biomarker of metabolic distress.

Conclusion

Metabolic distress after TBI is associated with a differential proteome that indicates cellular destruction during the acute phase of illness. This suggests that metabolic distress has immediate cellular consequences after TBI.

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Authors and Affiliations

  1. UCLA Department of Chemistry and Biochemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    R. Lakshmanan, J. A. Loo & A. J. Ytterberg

  2. UCLA Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    T. Drake & J. Leblanc

  3. UCLA Department of Neurosurgery and Neurology, David Geffen School of Medicine at UCLA, Ronald Reagan UCLA Medical Center, 757 Westwood Blvd, Room, RR 6236A, Los Angeles, CA, USA

    D. L. McArthur, M. Etchepare & P. M. Vespa

Authors
  1. R. Lakshmanan
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  2. J. A. Loo
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  3. T. Drake
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  4. J. Leblanc
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  5. A. J. Ytterberg
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  6. D. L. McArthur
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  7. M. Etchepare
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  8. P. M. Vespa
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Corresponding author

Correspondence to P. M. Vespa.

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Lakshmanan, R., Loo, J.A., Drake, T. et al. Metabolic Crisis After Traumatic Brain Injury is Associated with a Novel Microdialysis Proteome. Neurocrit Care 12, 324–336 (2010). https://doi.org/10.1007/s12028-010-9342-5

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  • DOI: https://doi.org/10.1007/s12028-010-9342-5

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