Metabolic crisis after traumatic brain injury is associated with a novel microdialysis proteome.
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 c...
| Published in: | Neurocritical Care Vol. 12; no. 3; pp. 324 - 337 |
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| Main Authors: | , , , , , , , , , , , , , , , |
| Format: | research Journal Article |
| Published: |
Springer Nature
Jun2010
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105189987&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105189987 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 15416933 1WYA jtl: Neurocritical Care issn: 15416933 maglogo: N pubinfo: dt: Jun2010 vid: 12 iid: 3 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 105189987 NLM20225002 2010643371 10.1007/s12028-010-9342-5 NLM20225002 PMC4347948 105189987 ppf: 324 ppct: 13 formats: tig: atl: Metabolic crisis after traumatic brain injury is associated with a novel microdialysis proteome. aug: au: Lakshmanan R Loo JA Drake T Leblanc J Ytterberg AJ McArthur DL Etchepare M Vespa PM Lakshmanan, R Loo, J A Drake, T Leblanc, J Ytterberg, A J McArthur, D L Etchepare, M Vespa, P M affil: UCLA Department of Chemistry and Biochemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA sug: subj: Brain Physiopathology Brain Injuries Physiopathology Energy Metabolism Physiology Dialysis Equipment and Supplies Monitoring, Physiologic Equipment and Supplies Proteomics Signal Processing, Computer Assisted Equipment and Supplies Blood Glucose Metabolism Cerebral Ischemia Diagnosis Cerebral Ischemia Physiopathology Cerebral Hemorrhage Diagnosis Cerebral Hemorrhage Physiopathology Interstitial Fluid Physiology Prospective Studies Frontal Lobe Physiopathology Glasgow Coma Scale Human Hypoglycemia Diagnosis Hypoglycemia Physiopathology Intracranial Pressure Physiology Lactic Acid Blood Magnetic Resonance Imaging Carboxylic Acids Blood Reference Values Mass Spectrometry Equipment and Supplies Temporal Lobe Physiopathology Tomography, X-Ray Computed ab: 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 microM, 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. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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