Density of TMEM119‑positive microglial cells in postmortem cerebrospinal fluid as a surrogate marker for assessing complex neuropathological processes in the CNS

Date

2022

Authors

Bohnert, Simone
Trella, Stefanie
Preiß, Ulrich
Heinsen, Helmut
Bohnert, Michael
Zwirner, Johann
Tremblay, Marie‑Ève
Monoranu, Camelia-Maria
Ondruschka, Benjamin

Journal Title

Journal ISSN

Volume Title

Publisher

International Journal of Legal Medicine

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.

Description

We would like to thank the technical assistants Heiko Besenfelder and Max Perschneck, Institute of Forensic Medicine, University of Wuerzburg, for their excellent support in collecting the specimens, Michaela Hartmann, Department of Neuropathology, Institute of Pathology, University of Wuerzburg, as well as the team of the CSF laboratory of the Neurological University Hospital for their help with the preparations and stains. The authors would also like to thank Gerdi Zimmermann (Commissioned Sworn Translator, Gundelfingen, Germany) for correcting the English language of the manuscript. This paper is dedicated to Donata, the daughter of SB.

Keywords

Cerebrospinal fluid, Forensic neuropathology, Forensic neurotraumatology, Immunohistochemistry, Immunocytochemistry, Biomarker

Citation

Bohnert, S., Trella, S., Preiß, U., Heinsen, H., Bohnert, M., Zwirner, J., ... Ondruschka, B. (2022). Density of TMEM119-positive microglial cells in postmortem cerebrospinal fluid as a surrogate marker for assessing complex neuropathological processes in the CNS. International Journal of Legal Medicine, 136, 1841-1850. https://doi.org/10.1007/s00414-022-02863-5