Cited by 75Traumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury ResearchAutomotive and Human Injury Biomechanics

New astroglial injury-defined biomarkers for neurotrauma assessment

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Halford, Julia, Shen, Sean, Itamura, Kyohei, Levine, Jaclynn, Chong, Albert C, Czerwieniec, Gregg, Glenn, Thomas C, Hovda, David A +6 more·2017·Journal of Cerebral Blood Flow & Metabolism

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.

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Crossref · 10.1177/0271678x17724681

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  • Proteins released by injured astrocytes are currently being considered as fluid biomarkers of neurological trauma.

    “proteins released by injured astrocytes are currently being considered as fluid biomarkers of neurological trauma31”

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Authors
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.
Affiliations
  • University of California, Los Angeles (US)
  • Department of Neurosurgery, Brain Injury Research Center, Department of Molecular and Medical Pharmacology
  • Jackson Memorial Hospital (US)
  • University of Miami (US)
  • University of Messina (IT)
Corresponding author
Wanner, Ina-Beate
Venue
Journal of Cerebral Blood Flow & Metabolism
Published
2017-08-17
Volume
37
Issue
10
Pages
3278-3299
ISSN
  • 0271-678X (ISSN-L)
  • 1559-7016
OpenAlex
W2748412799
Cited by
75
References
121
Citations by year
2026: 1 · 2025: 7 · 2024: 6 · 2023: 12 · 2022: 11 · 2021: 13 · 2020: 11 · 2019: 5 · 2018: 6 · 2017: 3
FWCI
4.76
Type
journal article
Language
en
Open access
Locations
  • Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Automotive and Human Injury Biomechanics
Keywords
traumatic brain injury, cerebrospinal fluid biomarkers, CSF proteome, aldolase C, brain lipid-binding protein, PEA-15, glutamine synthetase, astrocyte injury, biomarker kinetics, mild traumatic brain injury, cell death
MeSH terms
Brain Injuries, Traumatic, Fatty Acid-Binding Protein 7, Astrocytes, Brain Concussion, Cells, Cultured, Fructose-Bisphosphate Aldolase, Humans, Kinetics, Phosphoproteins, Biomarkers, Proteome, Tumor Suppressor Proteins, Intracellular Signaling Peptides and Proteins, Apoptosis Regulatory Proteins

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