New astroglial injury-defined biomarkers for neurotrauma assessment

Julia Halford, Sean Shen, Kyohei Itamura, Jaclynn Levine, Albert C. Chong, Gregg Czerwieniec, Thomas C. Glenn, David A. Hovda, Paul Vespa, Ross Bullock, W. Dalton Dietrich, Stefania Mondello, Joseph A. Loo, Ina Beate Wanner

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Traumatic brain injury (TBI) is an expanding public health epidemic with pathophysiology that is difficult to diagnose and thus treat. TBI biomarkers should assess patients across severities and reveal pathophysiology, but currently, their kinetics and specificity are unclear. No single ideal TBI biomarker exists. We identified new candidates from a TBI CSF proteome by selecting trauma-released, astrocyte-enriched proteins including aldolase C (ALDOC), its 38kD breakdown product (BDP), brain lipid binding protein (BLBP), astrocytic phosphoprotein (PEA15), glutamine synthetase (GS) and new 18-25kD-GFAP-BDPs. Their levels increased over four orders of magnitude in severe TBI CSF. First post-injury week, ALDOC levels were markedly high and stable. Short-lived BLBP and PEA15 related to injury progression. ALDOC, BLBP and PEA15 appeared hyper-acutely and were similarly robust in severe and mild TBI blood; 25kD-GFAP-BDP appeared overnight after TBI and was rarely present after mild TBI. Using a human culture trauma model, we investigated biomarker kinetics. Wounded (mechanoporated) astrocytes released ALDOC, BLBP and PEA15 acutely. Delayed cell death corresponded with GFAP release and proteolysis into small GFAP-BDPs. Associating biomarkers with cellular injury stages produced astroglial injury-defined (AID) biomarkers that facilitate TBI assessment, as neurological deficits are rooted not only in death of CNS cells, but also in their functional compromise.

Original languageEnglish (US)
Pages (from-to)3278-3299
Number of pages22
JournalJournal of Cerebral Blood Flow and Metabolism
Volume37
Issue number10
DOIs
StatePublished - Oct 1 2017

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Biomarkers
Fructose-Bisphosphate Aldolase
Wounds and Injuries
Brain Concussion
Astrocytes
Cell Death
Glutamate-Ammonia Ligase
Phosphoproteins
Proteome
Traumatic Brain Injury
Proteolysis
Public Health
Fatty Acid-Binding Protein 7
Proteins

Keywords

  • Astrocytes
  • brain trauma
  • cell culture
  • cerebrospinal fluid
  • exploratory factor analysis
  • proteomics

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Halford, J., Shen, S., Itamura, K., Levine, J., Chong, A. C., Czerwieniec, G., ... Wanner, I. B. (2017). New astroglial injury-defined biomarkers for neurotrauma assessment. Journal of Cerebral Blood Flow and Metabolism, 37(10), 3278-3299. https://doi.org/10.1177/0271678X17724681

New astroglial injury-defined biomarkers for neurotrauma assessment. / Halford, Julia; Shen, Sean; Itamura, Kyohei; Levine, Jaclynn; Chong, Albert C.; Czerwieniec, Gregg; Glenn, Thomas C.; Hovda, David A.; Vespa, Paul; Bullock, Ross; Dalton Dietrich, W.; Mondello, Stefania; Loo, Joseph A.; Wanner, Ina Beate.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 37, No. 10, 01.10.2017, p. 3278-3299.

Research output: Contribution to journalArticle

Halford, J, Shen, S, Itamura, K, Levine, J, Chong, AC, Czerwieniec, G, Glenn, TC, Hovda, DA, Vespa, P, Bullock, R, Dalton Dietrich, W, Mondello, S, Loo, JA & Wanner, IB 2017, 'New astroglial injury-defined biomarkers for neurotrauma assessment', Journal of Cerebral Blood Flow and Metabolism, vol. 37, no. 10, pp. 3278-3299. https://doi.org/10.1177/0271678X17724681
Halford J, Shen S, Itamura K, Levine J, Chong AC, Czerwieniec G et al. New astroglial injury-defined biomarkers for neurotrauma assessment. Journal of Cerebral Blood Flow and Metabolism. 2017 Oct 1;37(10):3278-3299. https://doi.org/10.1177/0271678X17724681
Halford, Julia ; Shen, Sean ; Itamura, Kyohei ; Levine, Jaclynn ; Chong, Albert C. ; Czerwieniec, Gregg ; Glenn, Thomas C. ; Hovda, David A. ; Vespa, Paul ; Bullock, Ross ; Dalton Dietrich, W. ; Mondello, Stefania ; Loo, Joseph A. ; Wanner, Ina Beate. / New astroglial injury-defined biomarkers for neurotrauma assessment. In: Journal of Cerebral Blood Flow and Metabolism. 2017 ; Vol. 37, No. 10. pp. 3278-3299.
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