Institute of Forensic Medicine, University of Wuerzburg, Versbacher Str. 3, 97078, Wuerzburg, Germany.
Department of Radiation Oncology, Friedrich Alexander University of Erlangen-Nürnberg, Universitätsstr. 27, 91054, Erlangen, Germany.
Int J Legal Med. 2020 Nov;134(6):2167-2176. doi: 10.1007/s00414-020-02384-z. Epub 2020 Jul 27.
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.
本研究旨在对神经炎症进行精细化分析，包括 TMEM119 作为一种有用的小胶质细胞特异性标志物，用于法医评估创伤性死因，例如创伤性脑损伤（TBI）。从尸检中获得人脑组织样本，并分为致死性 TBI 病例（n=25），并根据创伤存活时间分为三组，并与年龄、性别和死后间隔匹配的突发性心血管死亡病例对照组（n=23）进行比较。收集靠近皮质挫伤和周围白质的脑组织样本以及对侧未受伤的脑干和小脑样本，并使用 TMEM119、CD206 和 CCR2 抗体进行免疫组织化学染色。我们可以在急性 TBI 死亡病例中记录到最多的 TMEM119 阳性细胞，与对照组相比差异具有高度显著性。CCR2 阳性单核细胞在 TBI 病例的皮质样本中的细胞计数明显高于对照组，随着时间的推移，免疫阳性细胞的数量逐渐增加。CD206 阳性 M2 小胶质细胞的数量随存活时间的延长而增加。在存活 3 天后，与对照组相比，所有四个研究区域的细胞数量均显著增加。总之，我们验证了一种特异性强、表达稳定、反应迅速的小胶质细胞标志物 TMEM119，它可以将小胶质细胞与常驻和浸润的巨噬细胞区分开来，因此为估计 TBI 后最小存活时间提供了巨大潜力。
