New astroglial injury-defined biomarkers for neurotrauma assessment

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 bi...

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Bibliographic Details
Published in:Journal of cerebral blood flow and metabolism 2017-10, Vol.37 (10), p.3278-3299
Main Authors: Halford, Julia, Shen, Sean, Itamura, Kyohei, Levine, Jaclynn, Chong, Albert C, Czerwieniec, Gregg, Glenn, Thomas C, Hovda, David A, Vespa, Paul, Bullock, Ross, Dietrich, W Dalton, Mondello, Stefania, Loo, Joseph A, Wanner, Ina-Beate
Format: Article
Language:English
Subjects:
Apoptosis Regulatory Proteins
Astrocytes - chemistry
Astrocytes - pathology
Biomarkers - analysis
Brain Concussion
Brain Injuries, Traumatic - cerebrospinal fluid
Brain Injuries, Traumatic - diagnosis
Cells, Cultured
Fatty Acid-Binding Protein 7 - blood
Fructose-Bisphosphate Aldolase - blood
Humans
Intracellular Signaling Peptides and Proteins - blood
Kinetics
Phosphoproteins - blood
Proteome - analysis
Tumor Suppressor Proteins - blood
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Summary: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.
ISSN:0271-678X
1559-7016
DOI:10.1177/0271678X17724681