TY - JOUR A1 - Trautz, Florian A1 - Franke, Heike A1 - Bohnert, Simone A1 - Hammer, Niels A1 - Müller, Wolf A1 - Stassart, Ruth A1 - Tse, Rexson A1 - Zwirner, Johann A1 - Dreßler, Jan A1 - Ondruschka, Benjamin T1 - Survival-time dependent increase in neuronal IL-6 and astroglial GFAP expression in fatally injured human brain tissue JF - Scientific Reports N2 - Knowledge on trauma survival time prior to death following a lethal traumatic brain injury (TBI) may be essential for legal purposes. Immunohistochemistry studies might allow to narrow down this survival interval. The biomarkers interleukin-6 (IL-6) and glial fibrillary acidic protein (GFAP) are well known in the clinical setting for their usability in TBI prediction. Here, both proteins were chosen in forensics to determine whether neuronal or glial expression in various brain regions may be associated with the cause of death and the survival time prior to death following TBI. IL-6 positive neurons, glial cells and GFAP positive astrocytes all concordantly increase with longer trauma survival time, with statistically significant changes being evident from three days post-TBI (p < 0.05) in the pericontusional zone, irrespective of its definite cortical localization. IL-6 staining in neurons increases significantly in the cerebellum after trauma, whereas increasing GFAP positivity is also detected in the cortex contralateral to the focal lesion. These systematic chronological changes in biomarkers of pericontusional neurons and glial cells allow for an estimation of trauma survival time. Higher numbers of IL-6 and GFAP-stained cells above threshold values in the pericontusional zone substantiate the existence of fatal traumatic changes in the brain with reasonable certainty. KW - cell death in the nervous system KW - diagnostic markers KW - outcomes research Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229037 VL - 9 ER - TY - JOUR A1 - Zwirner, Johann A1 - Anders, Sven A1 - Bohnert, Simone A1 - Burkhardt, Ralph A1 - Da Broi, Ugo A1 - Hammer, Niels A1 - Pohlers, Dirk A1 - Tse, Rexson A1 - Ondruschka, Benjamin T1 - Screening for fatal traumatic brain injuries in cerebrospinal fluid using blood-validated CK and CK−MB immunoassays JF - Biomolecules N2 - A single, specific, sensitive biochemical biomarker that can reliably diagnose a traumatic brain injury (TBI) has not yet been found, but combining different biomarkers would be the most promising approach in clinical and postmortem settings. In addition, identifying new biomarkers and developing laboratory tests can be time-consuming and economically challenging. As such, it would be efficient to use established clinical diagnostic assays for postmortem biochemistry. In this study, postmortem cerebrospinal fluid samples from 45 lethal TBI cases and 47 controls were analyzed using commercially available blood-validated assays for creatine kinase (CK) activity and its heart-type isoenzyme (CK–MB). TBI cases with a survival time of up to two hours showed an increase in both CK and CK–MB with moderate (CK–MB: AUC = 0.788, p < 0.001) to high (CK: AUC = 0.811, p < 0.001) diagnostic accuracy. This reflected the excessive increase of the brain-type CK isoenzyme (CK–BB) following a TBI. The results provide evidence that CK immunoassays can be used as an adjunct quantitative test aid in diagnosing acute TBI-related fatalities. KW - cerebrospinal fluid KW - creatine kinase KW - fatal traumatic brain injury KW - postmortem biochemistry Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242769 SN - 2218-273X VL - 11 IS - 7 ER - TY - JOUR A1 - Zwirner, Johann A1 - Bohnert, Simone A1 - Franke, Heike A1 - Garland, Jack A1 - Hammer, Niels A1 - Möbius, Dustin A1 - Tse, Rexson A1 - Ondruschka, Benjamin T1 - Assessing protein biomarkers to detect lethal acute traumatic brain injuries in cerebrospinal fluid JF - Biomolecules N2 - 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; R\(^2\) = 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. KW - biomarker combination KW - glial fibrillary acidic protein KW - interleukin-6 KW - post mortem biochemistry KW - traumatic brain injury Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248587 SN - 2218-273X VL - 11 IS - 11 ER -