Assessing Protein Biomarkers to Detect Lethal Acute Traumatic Brain Injuries in Cerebrospinal Fluid
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-10-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/11/11/1577 |
| _version_ | 1827677274872217600 |
|---|---|
| author | Johann Zwirner Simone Bohnert Heike Franke Jack Garland Niels Hammer Dustin Möbius Rexson Tse Benjamin Ondruschka |
| author_facet | Johann Zwirner Simone Bohnert Heike Franke Jack Garland Niels Hammer Dustin Möbius Rexson Tse Benjamin Ondruschka |
| author_sort | Johann Zwirner |
| collection | DOAJ |
| description | 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 (<i>p</i> = 0.002; R<sup>2</sup> = 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. |
| first_indexed | 2024-03-10T05:40:48Z |
| format | Article |
| id | doaj.art-f04136b9e9104d38a84342133a045fe5 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T05:40:48Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-f04136b9e9104d38a84342133a045fe52023-11-22T22:33:13ZengMDPI AGBiomolecules2218-273X2021-10-011111157710.3390/biom11111577Assessing Protein Biomarkers to Detect Lethal Acute Traumatic Brain Injuries in Cerebrospinal FluidJohann Zwirner0Simone Bohnert1Heike Franke2Jack Garland3Niels Hammer4Dustin Möbius5Rexson Tse6Benjamin Ondruschka7Department of Anatomy, University of Otago, Dunedin 9016, New ZealandInstitute of Forensic Medicine, University of Wuerzburg, 97078 Wuerzburg, GermanyRudolf Boehm Institute of Pharmacology and Toxicology, University of Leipzig, 04107 Leipzig, GermanyForensic and Analytical Science Service, NSW Health Pathology, Lidcombe 2141, AustraliaInstitute of Macroscopic and Clinical Anatomy, University of Graz, 8010 Graz, AustriaInstitute of Legal Medicine, University Medical Center Hamburg-Eppendorf, 22529 Hamburg, GermanyDepartment of Forensic Pathology, LabPLUS, Auckland City Hospital, Auckland 1148, New ZealandInstitute of Legal Medicine, University Medical Center Hamburg-Eppendorf, 22529 Hamburg, GermanyDiagnosing 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 (<i>p</i> = 0.002; R<sup>2</sup> = 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.https://www.mdpi.com/2218-273X/11/11/1577biomarker combinationglial fibrillary acidic proteininterleukin-6post mortem biochemistrytraumatic brain injury |
| spellingShingle | Johann Zwirner Simone Bohnert Heike Franke Jack Garland Niels Hammer Dustin Möbius Rexson Tse Benjamin Ondruschka Assessing Protein Biomarkers to Detect Lethal Acute Traumatic Brain Injuries in Cerebrospinal Fluid Biomolecules biomarker combination glial fibrillary acidic protein interleukin-6 post mortem biochemistry traumatic brain injury |
| title | Assessing Protein Biomarkers to Detect Lethal Acute Traumatic Brain Injuries in Cerebrospinal Fluid |
| title_full | Assessing Protein Biomarkers to Detect Lethal Acute Traumatic Brain Injuries in Cerebrospinal Fluid |
| title_fullStr | Assessing Protein Biomarkers to Detect Lethal Acute Traumatic Brain Injuries in Cerebrospinal Fluid |
| title_full_unstemmed | Assessing Protein Biomarkers to Detect Lethal Acute Traumatic Brain Injuries in Cerebrospinal Fluid |
| title_short | Assessing Protein Biomarkers to Detect Lethal Acute Traumatic Brain Injuries in Cerebrospinal Fluid |
| title_sort | assessing protein biomarkers to detect lethal acute traumatic brain injuries in cerebrospinal fluid |
| topic | biomarker combination glial fibrillary acidic protein interleukin-6 post mortem biochemistry traumatic brain injury |
| url | https://www.mdpi.com/2218-273X/11/11/1577 |
| work_keys_str_mv | AT johannzwirner assessingproteinbiomarkerstodetectlethalacutetraumaticbraininjuriesincerebrospinalfluid AT simonebohnert assessingproteinbiomarkerstodetectlethalacutetraumaticbraininjuriesincerebrospinalfluid AT heikefranke assessingproteinbiomarkerstodetectlethalacutetraumaticbraininjuriesincerebrospinalfluid AT jackgarland assessingproteinbiomarkerstodetectlethalacutetraumaticbraininjuriesincerebrospinalfluid AT nielshammer assessingproteinbiomarkerstodetectlethalacutetraumaticbraininjuriesincerebrospinalfluid AT dustinmobius assessingproteinbiomarkerstodetectlethalacutetraumaticbraininjuriesincerebrospinalfluid AT rexsontse assessingproteinbiomarkerstodetectlethalacutetraumaticbraininjuriesincerebrospinalfluid AT benjaminondruschka assessingproteinbiomarkerstodetectlethalacutetraumaticbraininjuriesincerebrospinalfluid |