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

15 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Halford, J., Shen, S., Itamura, K., Levine, J., Chong, A. C., Czerwieniec, G., Glenn, T. C., Hovda, D. A., Vespa, P., Bullock, R., Dietrich, W. D., Mondello, S., Loo, J. A., & 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