TMEM119 as a specific marker of microglia reaction in traumatic brain injury in postmortem examination
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ORIGINAL ARTICLE
TMEM119 as a specific marker of microglia reaction in traumatic brain injury in postmortem examination Simone Bohnert 1 & Anja Seiffert 1 & Stefanie Trella 1 & Michael Bohnert 1 & Luitpold Distel 2 & Benjamin Ondruschka 3 & Camelia-Maria Monoranu 4 Received: 17 April 2020 / Accepted: 23 July 2020 # The Author(s) 2020
Abstract The aim of the present study was a refined analysis of neuroinflammation including TMEM119 as a useful microglia-specific marker in forensic assessments of traumatic causes of death, e.g., traumatic brain injury (TBI). Human brain tissue samples were obtained from autopsies and divided into cases with lethal TBI (n = 25) and subdivided into three groups according to their trauma survival time and compared with an age-, gender-, and postmortem interval-matched cohort of sudden cardiovascular fatalities as controls (n = 23). Brain tissue samples next to cortex contusions and surrounding white matter as well as samples of the ipsilateral uninjured brain stem and cerebellum were collected and stained immunohistochemically with antibodies against TMEM119, CD206, and CCR2. We could document the highest number of TMEM119-positive cells in acute TBI death with highly significant differences to the control numbers. CCR2-positive monocytes showed a significantly higher cell count in the cortex samples of TBI cases than in the controls with an increasing number of immunopositive cells over time. The number of CD206-positive M2 microglial cells increased survival time-dependent. After 3 days of survival, the cell number increased significantly in all four regions investigated compared with controls. In sum, we validate a specific and robustly expressed as well as fast reacting microglia marker, TMEM119, which distinguishes microglia from resident and infiltrating macrophages and thus offers a great potential for the estimation of the minimum survival time after TBI. Keywords Cerebrospinal fluid . Forensic neuropathology . Forensic neurotraumatology . Immunohistochemistry . Immunocytochemistry . Biomarker
Introduction Benjamin Ondruschka and Camelia-Maria Monoranu contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00414-020-02384-z) contains supplementary material, which is available to authorized users. * Simone Bohnert [email protected] 1
Institute of Forensic Medicine, University of Wuerzburg, Versbacher Str. 3, 97078 Wuerzburg, Germany
2
Department of Radiation Oncology, Friedrich Alexander University of Erlangen-Nürnberg, Universitätsstr. 27, 91054 Erlangen, Germany
3
Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Butenfeld 34, 22529 Hamburg, Germany
4
Department of Neuropathology, Institute of Pathology, University of Wuerzburg, Josef-Schneider Str. 2, 97080 Wuerzburg, Germany
According to the Federal Statistical Office, more than 5000 individuals die from sequelae of traumatic brain injury (TBI) in Germany every year, and a relevant part of these deaths i
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