@article{BohnertTrellaPreissetal.2022,
  author    = {Bohnert, Simone and Trella, Stefanie and Preiß, Ulrich and Heinsen, Helmut and Bohnert, Michael and Zwirner, Johann and Tremblay, Marie-{\`E}ve and Monoranu, Camelia-Maria and Ondruschka, Benjamin},
  title     = {Density of TMEM119-positive microglial cells in postmortem cerebrospinal fluid as a surrogate marker for assessing complex neuropathological processes in the CNS},
  series = {International Journal of Legal Medicine},
  volume    = {136},
  journal   = {International Journal of Legal Medicine},
  number    = {6},
  doi       = {10.1007/s00414-022-02863-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325009},
  pages     = {1841-1850},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{ZwirnerAndersBohnertetal.2021,
  author    = {Zwirner, Johann and Anders, Sven and Bohnert, Simone and Burkhardt, Ralph and Da Broi, Ugo and Hammer, Niels and Pohlers, Dirk and Tse, Rexson and Ondruschka, Benjamin},
  title     = {Screening for fatal traumatic brain injuries in cerebrospinal fluid using blood-validated CK and CK-MB immunoassays},
  series = {Biomolecules},
  volume    = {11},
  journal   = {Biomolecules},
  number    = {7},
  issn      = {2218-273X},
  doi       = {10.3390/biom11071061},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242769},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}
@article{ZwirnerBohnertFrankeetal.2021,
  author    = {Zwirner, Johann and Bohnert, Simone and Franke, Heike and Garland, Jack and Hammer, Niels and M{\"o}bius, Dustin and Tse, Rexson and Ondruschka, Benjamin},
  title     = {Assessing protein biomarkers to detect lethal acute traumatic brain injuries in cerebrospinal fluid},
  series = {Biomolecules},
  volume    = {11},
  journal   = {Biomolecules},
  number    = {11},
  issn      = {2218-273X},
  doi       = {10.3390/biom11111577},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248587},
  year      = {2021},
  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; 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.},
  language  = {en}
}