TY - JOUR A1 - Mittal, Pawan A1 - Bohnert, Michael T1 - Intramuscular hemorrhages in the pathway of an electric current through the body - two case reports JF - Forensic Science, Medicine and Pathology N2 - Intramuscular hemorrhages at autopsy can have a variety of traumatic as well as non-traumatic causes, but their recognition in electrical deaths is almost a rarity. We report on two autopsy cases of electrical fatalities, the first relating to a portion of the right upper human extremity, consisting (only) of the forearm and hand, while the other case relates to a female child who died after a high voltage electrical shock. In both cases, layered dissection of the upper limb revealed fresh intramuscular hemorrhages in the skeletal muscles that could be topographically related to the path taken by the current through the body. Externally visible electric marks were present in both cases. The hemorrhages were most likely caused by current-induced tetanic muscle contractions, producing an internal muscle trauma with rupture of fibers and bleedings. In complex situations, such as inconspicuous marks or a complete lack of visible signs on the body, the finding may be helpful in solving the case in consideration of the case history and circumstances. The vitality, topography, and pattern of the hemorrhages are discussed in the light of the available literature. KW - electrocution KW - layered dissection KW - intramuscular hemorrhage KW - tetany Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325019 VL - 19 IS - 1 ER - TY - JOUR A1 - Löhr, Mario A1 - Härtig, Wolfgang A1 - Schulze, Almut A1 - Kroiß, Matthias A1 - Sbiera, Silviu A1 - Lapa, Constantin A1 - Mages, Bianca A1 - Strobel, Sabrina A1 - Hundt, Jennifer Elisabeth A1 - Bohnert, Simone A1 - Kircher, Stefan A1 - Janaki-Raman, Sudha A1 - Monoranu, Camelia-Maria T1 - SOAT1: A suitable target for therapy in high-grade astrocytic glioma? JF - International Journal of Molecular Sciences N2 - Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum cholesterol to esters for storage in lipid droplets (LD), serves as a target for the orphan drug mitotane to treat adrenocortical carcinoma. Inhibition of SOAT1 also suppresses GBM growth. Here, we refined SOAT1-expression in GBM and IDH-mutant astrocytoma, CNS WHO grade 4 (HGA), and assessed the distribution of LD in these tumors. Twenty-seven GBM and three HGA specimens were evaluated by multiple GFAP, Iba1, IDH1 R132H, and SOAT1 immunofluorescence labeling as well as Oil Red O staining. To a small extent SOAT1 was expressed by tumor cells in both tumor entities. In contrast, strong expression was observed in glioma-associated macrophages. Triple immunofluorescence labeling revealed, for the first time, evidence for SOAT1 colocalization with Iba1 and IDH1 R132H, respectively. Furthermore, a notable difference in the amount of LD between GBM and HGA was observed. Therefore, SOAT1 suppression might be a therapeutic option to target GBM and HGA growth and invasiveness. In addition, the high expression in cells related to neuroinflammation could be beneficial for a concomitant suppression of protumoral microglia/macrophages. KW - SOAT1 KW - glioblastoma KW - astrocytoma KW - IDH1/2 KW - lipid droplets KW - mitotane KW - targeted therapy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284178 SN - 1422-0067 VL - 23 IS - 7 ER - TY - JOUR A1 - Schmitt, Andrea A1 - Tatsch, Laura A1 - Vollhardt, Alisa A1 - Schneider-Axmann, Thomas A1 - Raabe, Florian J. A1 - Roell, Lukas A1 - Heinsen, Helmut A1 - Hof, Patrick R. A1 - Falkai, Peter A1 - Schmitz, Christoph T1 - Decreased oligodendrocyte number in hippocampal subfield CA4 in schizophrenia: a replication study JF - Cells N2 - Hippocampus-related cognitive deficits in working and verbal memory are frequent in schizophrenia, and hippocampal volume loss, particularly in the cornu ammonis (CA) subregions, was shown by magnetic resonance imaging studies. However, the underlying cellular alterations remain elusive. By using unbiased design-based stereology, we reported a reduction in oligodendrocyte number in CA4 in schizophrenia and of granular neurons in the dentate gyrus (DG). Here, we aimed to replicate these findings in an independent sample. We used a stereological approach to investigate the numbers and densities of neurons, oligodendrocytes, and astrocytes in CA4 and of granular neurons in the DG of left and right hemispheres in 11 brains from men with schizophrenia and 11 brains from age- and sex-matched healthy controls. In schizophrenia, a decreased number and density of oligodendrocytes was detected in the left and right CA4, whereas mean volumes of CA4 and the DG and the numbers and density of neurons, astrocytes, and granular neurons were not different in patients and controls, even after adjustment of variables because of positive correlations with postmortem interval and age. Our results replicate the previously described decrease in oligodendrocytes bilaterally in CA4 in schizophrenia and point to a deficit in oligodendrocyte maturation or a loss of mature oligodendrocytes. These changes result in impaired myelination and neuronal decoupling, both of which are linked to altered functional connectivity and subsequent cognitive dysfunction in schizophrenia. KW - schizophrenia KW - hippocampus KW - CA4 KW - dentate gyrus KW - postmortem KW - stereology KW - oligodendrocyte KW - neuron Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290360 SN - 2073-4409 VL - 11 IS - 20 ER - TY - JOUR A1 - Bohnert, Simone A1 - Trella, Stefanie A1 - Preiß, Ulrich A1 - Heinsen, Helmut A1 - Bohnert, Michael A1 - Zwirner, Johann A1 - Tremblay, Marie-Ève A1 - Monoranu, Camelia-Maria A1 - Ondruschka, Benjamin T1 - Density of TMEM119-positive microglial cells in postmortem cerebrospinal fluid as a surrogate marker for assessing complex neuropathological processes in the CNS JF - International Journal of Legal Medicine N2 - Routine coronal paraffin-sections through the dorsal frontal and parieto-occipital cortex of a total of sixty cases with divergent causes of death were immunohistochemically (IHC) stained with an antibody against TMEM119. Samples of cerebrospinal fluid (CSF) of the same cases were collected by suboccipital needle-puncture, subjected to centrifugation and processed as cytospin preparations stained with TMEM119. Both, cytospin preparations and sections were subjected to computer-assisted density measurements. The density of microglial TMEM119-positive cortical profiles correlated with that of cytospin results and with the density of TMEM119-positive microglial profiles in the medullary layer. There was no statistically significant correlation between the density of medullary TMEM119-positive profiles and the cytospin data. Cortical microglial cells were primarily encountered in supragranular layers I, II, and IIIa and in infragranular layers V and VI, the region of U-fibers and in circumscribed foci or spread in a diffuse manner and high density over the white matter. We have evidence that cortical microglia directly migrate into CSF without using the glympathic pathway. Microglia in the medullary layer shows a strong affinity to the adventitia of deep vessels in the myelin layer. Selected rapidly fatal cases including myocardial infarcts and drowning let us conclude that microglia in cortex and myelin layer can react rapidly and its reaction and migration is subject to pre-existing external and internal factors. Cytospin preparations proved to be a simple tool to analyze and assess complex changes in the CNS after rapid fatal damage. There is no statistically significant correlation between cytospin and postmortem interval. Therefore, the quantitative analyses of postmortem cytospins obviously reflect the neuropathology of the complete central nervous system. Cytospins provide forensic pathologists a rather simple and easy to perform method for the global assessment of CNS affliction. KW - cerebrospinal fluid KW - forensic neuropathology KW - forensic neurotraumatology KW - immunohistochemistry KW - immunocytochemistry KW - biomarker Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325009 VL - 136 IS - 6 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 - Bohnert, Simone A1 - Georgiades, Kosmas A1 - Monoranu, Camelia-Maria A1 - Bohnert, Michael A1 - Büttner, Andreas A1 - Ondruschka, Benjamin T1 - Quantitative evidence of suppressed TMEM119 microglial immunohistochemistry in fatal morphine intoxications JF - International Journal of Legal Medicine N2 - The aim of this pilot study was to investigate the diagnostic potential of TMEM119 as a useful microglia-specific marker in combination with immunostainings for phagocytic function and infiltrating capacity of monocytes in cases of lethal monosubstance intoxications by morphine (MOR), methamphetamine (METH), and of ethanol-associated death (ETH) respectively. Human brain tissue samples were obtained from forensic autopsies of cases with single substance abuse (MOR, n = 8; ETH, n = 10; METH, n = 9) and then compared to a cohort of cardiovascular fatalities as controls (n = 9). Brain tissue samples of cortex, white matter, and hippocampus were collected and stained immunohistochemically with antibodies against TMEM119, CD68KiM1P, and CCR2. We could document the lowest density of TMEM119-positive cells in MOR deaths with highly significant differences to the control densities in all three regions investigated. In ETH and METH deaths, the expression of TMEM119 was comparable to cell densities in controls. The results indicate that the immunoreaction in brain tissue is different in these groups depending on the drug type used for abuse. KW - immunohistochemistry KW - drug abuse KW - forensic neuropathology KW - neuroinflammation KW - neurotoxicity KW - microglia Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-266934 SN - 1437-1596 VL - 135 IS - 6 ER - TY - JOUR A1 - Bohnert, Simone A1 - Reinert, Christoph A1 - Trella, Stefanie A1 - Schmitz, Werner A1 - Ondruschka, Benjamin A1 - Bohnert, Michael T1 - Metabolomics in postmortem cerebrospinal fluid diagnostics: a state-of-the-art method to interpret central nervous system–related pathological processes JF - International Journal of Legal Medicine N2 - In the last few years, quantitative analysis of metabolites in body fluids using LC/MS has become an established method in laboratory medicine and toxicology. By preparing metabolite profiles in biological specimens, we are able to understand pathophysiological mechanisms at the biochemical and thus the functional level. An innovative investigative method, which has not yet been used widely in the forensic context, is to use the clinical application of metabolomics. In a metabolomic analysis of 41 samples of postmortem cerebrospinal fluid (CSF) samples divided into cohorts of four different causes of death, namely, cardiovascular fatalities, isoIated torso trauma, traumatic brain injury, and multi-organ failure, we were able to identify relevant differences in the metabolite profile between these individual groups. According to this preliminary assessment, we assume that information on biochemical processes is not gained by differences in the concentration of individual metabolites in CSF, but by a combination of differently distributed metabolites forming the perspective of a new generation of biomarkers for diagnosing (fatal) TBI and associated neuropathological changes in the CNS using CSF samples. KW - CSF KW - cerebrospinal fluid KW - forensic neuropathology KW - forensic neurotraumatology KW - biomarker KW - metabolomics Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235724 SN - 0937-9827 VL - 135 ER - TY - JOUR A1 - Bohnert, Simone A1 - Wirth, Christoph A1 - Schmitz, Werner A1 - Trella, Stefanie A1 - Monoranu, Camelia-Maria A1 - Ondruschka, Benjamin A1 - Bohnert, Michael T1 - Myelin basic protein and neurofilament H in postmortem cerebrospinal fluid as surrogate markers of fatal traumatic brain injury JF - International Journal of Legal Medicine N2 - The aim of this study was to investigate if the biomarkers myelin basic protein (MBP) and neurofilament-H (NF-H) yielded informative value in forensic diagnostics when examining cadaveric cerebrospinal fluid (CSF) biochemically via an enzyme-linked immunosorbent assay (ELISA) and comparing the corresponding brain tissue in fatal traumatic brain injury (TBI) autopsy cases by immunocytochemistry versus immunohistochemistry. In 21 trauma and 19 control cases, CSF was collected semi-sterile after suboccipital puncture and brain specimens after preparation. The CSF MBP (p = 0.006) and NF-H (p = 0.0002) levels after TBI were significantly higher than those in cardiovascular controls. Immunohistochemical staining against MBP and against NF-H was performed on cortical and subcortical samples from also biochemically investigated cases (5 TBI cases/5 controls). Compared to the controls, the TBI cases showed a visually reduced staining reaction against MBP or repeatedly ruptured neurofilaments against NF-H. Immunocytochemical tests showed MBP-positive phagocytizing macrophages in CSF with a survival time of > 24 h. In addition, numerous TMEM119-positive microglia could be detected with different degrees of staining intensity in the CSF of trauma cases. As a result, we were able to document that elevated levels of MBP and NF-H in the CSF should be considered as useful neuroinjury biomarkers of traumatic brain injury. KW - biofluid KW - CSF KW - cerebrospinal fluid KW - forensic neuropathology KW - forensic neurotraumatology KW - biomarker Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-266929 SN - 1437-1596 VL - 135 IS - 4 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 - TY - JOUR A1 - Jellinghaus, Katharina A1 - Scherer, Charlotte A1 - Stauffer, Edouard A1 - Urban, Petra A1 - Bohnert, Michael A1 - Kneubuehl, Beat P. T1 - Deadly injuries through recoilless anti-tank weapons while military shooting practice — two case studies from Germany and Switzerland JF - International Journal of Legal Medicine N2 - In this casuistry, two accidents from Germany and Switzerland are presented that happened during the shot of recoilless anti-tankweapons. In both cases, the injuries led to the death of two soldiers: A 22-year-old soldier in Germany was struck by the countermass of a so-called Davis gun which had been fired by a comrade during a firing exercise; he died from his severe injuries,especially in the abdominal part of the body. As a peculiarity of the wound morphology, it was found to be a thick-layered,metallic, gray material in the wound cavity, which corresponded to the material of the counter mass that was ejected opposite tothe shooting direction. The other case took place in Switzerland, where a 24-year-old soldier was seriously injured during anexercise with portable anti-tank rockets. At the time the shot was fired, he stood behind the launcher and was hit by the propulsionjet of the rocket motor. He died as well from his severe injuries, which were located at the chest done by the gas jet and by the veryhigh pressure. In both cases, two different causes of death were present: massive blunt violence in the first case versus a jet of hotgases of very high speed and temperature in the second case. KW - Anti-tank weapon KW - Military shooting KW - Davis gun KW - Anti-tank rocket KW - Ballistics Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232727 SN - 0937-9827 VL - 134 ER -