Assessing Protein Biomarkers to Detect Lethal Acute Traumatic Brain Injuries in Cerebrospinal Fluid

Johann Zwirner; Simone Bohnert; Heike Franke; Jack Garland; Niels Hammer; Dustin Möbius; Rexson Tse; Benjamin Ondruschka

doi:10.3390/biom11111577

Assessing Protein Biomarkers to Detect Lethal Acute Traumatic Brain Injuries in Cerebrospinal Fluid

Biomolecules. 2021 Oct 25;11(11):1577. doi: 10.3390/biom11111577.

Authors

Johann Zwirner^{1

2

3}, Simone Bohnert⁴, Heike Franke⁵, Jack Garland⁶, Niels Hammer^{7

8

9}, Dustin Möbius², Rexson Tse¹⁰, Benjamin Ondruschka²

Affiliations

¹ Department of Anatomy, University of Otago, Dunedin 9016, New Zealand.
² Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, 22529 Hamburg, Germany.
³ Institute of Legal Medicine, University of Leipzig, 04103 Leipzig, Germany.
⁴ Institute of Forensic Medicine, University of Wuerzburg, 97078 Wuerzburg, Germany.
⁵ Rudolf Boehm Institute of Pharmacology and Toxicology, University of Leipzig, 04107 Leipzig, Germany.
⁶ Forensic and Analytical Science Service, NSW Health Pathology, Lidcombe 2141, Australia.
⁷ Institute of Macroscopic and Clinical Anatomy, University of Graz, 8010 Graz, Austria.
⁸ Department of Orthopedic and Trauma Surgery, University of Leipzig, 04103 Leipzig, Germany.
⁹ Fraunhofer IWU, 47720 Dresden, Germany.
¹⁰ Department of Forensic Pathology, LabPLUS, Auckland City Hospital, Auckland 1148, New Zealand.

Abstract

Diagnosing traumatic brain injury (TBI) from body fluids in cases where there are no obvious external signs of impact would be useful for emergency physicians and forensic pathologists alike. None of the previous attempts has so far succeeded in establishing a single biomarker to reliably detect TBI with regards to the sensitivity: specificity ratio in a post mortem setting. This study investigated a combination of body fluid biomarkers (obtained post mortem), which may be a step towards increasing the accuracy of biochemical TBI detection. In this study, serum and cerebrospinal fluid (CSF) samples from 30 acute lethal TBI cases and 70 controls without a TBI-related cause of death were evaluated for the following eight TBI-related biomarkers: brain-derived neurotrophic factor (BDNF), ferritin, glial fibrillary acidic protein (GFAP), interleukin 6 (IL-6), lactate dehydrogenase, neutrophil gelatinase-associated lipocalin (NGAL), neuron-specific enolase and S100 calcium-binding protein B. Correlations among the individual TBI biomarkers were assessed, and a specificity-accentuated threshold value analysis was conducted for all biomarkers. Based on these values, a decision tree modelling approach was performed to assess the most accurate biomarker combination to detect acute lethal TBIs. The results showed that 92.45% of acute lethal TBIs were able to be diagnosed using a combination of IL-6 and GFAP in CSF. The probability of detecting an acute lethal TBI was moderately increased by GFAP alone and considerably increased by the remaining biomarkers. BDNF and NGAL were almost perfectly correlated (p = 0.002; R² = 0.944). This study provides evidence that acute lethal TBIs can be detected to a high degree of statistical accuracy using forensic biochemistry. The high inter-individual correlations of biomarkers may help to estimate the CSF concentration of an unknown biomarker, using extrapolation techniques.

Keywords: biomarker combination; glial fibrillary acidic protein; interleukin-6; post mortem biochemistry; traumatic brain injury.

MeSH terms

Biomarkers
Brain Injuries, Traumatic*
Glial Fibrillary Acidic Protein
Humans
Lipocalin-2
Phosphopyruvate Hydratase

Substances

Biomarkers
GFAP protein, human
Glial Fibrillary Acidic Protein
Lipocalin-2
Phosphopyruvate Hydratase