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尿液和唾液中微管相关蛋白tau(MAPT)的浓度作为创伤性脑损伤的潜在生物标志物与尸检中血脑屏障破坏的关系

Concentration of microtubule associated protein tau (MAPT) in urine and saliva as a potential biomarker of traumatic brain injury in relationship with blood-brain barrier disruption in postmortem examination.

作者信息

Olczak Mieszko, Poniatowski Łukasz A, Niderla-Bielińska Justyna, Kwiatkowska Magdalena, Chutorański Dominik, Tarka Sylwia, Wierzba-Bobrowicz Teresa

机构信息

Department of Forensic Medicine, Center for Biostructure Research, Medical University of Warsaw, Oczki 1, 02-007 Warsaw, Poland.

Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, W. K. Roentgena 5, 02-781 Warsaw, Poland.

出版信息

Forensic Sci Int. 2019 Aug;301:28-36. doi: 10.1016/j.forsciint.2019.05.010. Epub 2019 May 13.

Abstract

Traumatic brain injury (TBI) constitutes a frequent finding in medico-legal practice, including forensic autopsy and neuropathological examination. Despite clinico-scientific advances there is a need for identification of novel biomarkers considered for TBI diagnostics in ante- and postmortem cases. The role of MAPT protein as a biomarker in case of TBI was investigated in previous studies by examination of blood and cerebrospinal fluid obtained during forensic autopsies whereas less is known concerning its liberation and occurrence in other biofluids. The aim of this study was to elucidate and identify if elevated MAPT levels in other biofluids, such as urine, saliva, and vitreous body are also seen in TBI cases in population-based autopsy screening. The study was carried out using cases (n = 14) of severe head injury suspected as the cause of death and control cases (n = 13) of sudden death in the mechanism of cardiopulmonary failure. The biofluids, such as urine, saliva, and vitreous body were collected within ∼24 h after death and compared using ELISA test. Tissue specimens including brain and kidney were similarly collected during forensic autopsies. Brain specimens were stained immunohistologically with anti-Vimentin (V9) antibody and histologically using Mallory's trichrome method (to assess structural damage to blood-brain barrier elements) whereas kidney specimens were stained immunohistologically with anti-MAPT antibody (to assess the suitability of such a study in the diagnosis of TBI). In our study, we observed the elevated concentration levels of MAPT in saliva and urine. These changes were accompanied by damage to the structural elements of the blood-brain barrier (damage to the vascular endothelium and vascular basement membrane). According to this elevated cencentration levels of MAPT in this biofluids should be considered as TBI marker in postmortem examination even in cases where the head injury was not supposed to consist the direct cause of death.

摘要

创伤性脑损伤(TBI)在法医学实践中很常见,包括法医尸检和神经病理学检查。尽管临床科学取得了进展,但仍需要鉴定用于生前和死后TBI诊断的新型生物标志物。先前的研究通过检查法医尸检期间获得的血液和脑脊液,对微管相关蛋白Tau(MAPT)蛋白作为TBI生物标志物的作用进行了研究,而关于其在其他生物流体中的释放和存在情况知之甚少。本研究的目的是在基于人群的尸检筛查中,阐明和确定TBI病例中其他生物流体(如尿液、唾液和玻璃体)中MAPT水平是否也会升高。该研究使用了疑似因严重头部损伤导致死亡的病例(n = 14)和心肺功能衰竭机制下猝死的对照病例(n = 13)。在死亡后约24小时内收集尿液、唾液和玻璃体等生物流体,并使用酶联免疫吸附测定(ELISA)试验进行比较。在法医尸检期间同样收集包括脑和肾在内的组织标本。脑标本用抗波形蛋白(V9)抗体进行免疫组织化学染色,并用马洛里三色法进行组织学染色(以评估血脑屏障成分的结构损伤),而肾标本用抗MAPT抗体进行免疫组织化学染色(以评估此类研究在TBI诊断中的适用性)。在我们的研究中,我们观察到唾液和尿液中MAPT的浓度水平升高。这些变化伴随着血脑屏障结构成分的损伤(血管内皮和血管基底膜的损伤)。据此,即使在头部损伤不被认为是直接死因的情况下,这些生物流体中MAPT浓度水平的升高也应被视为死后检查中的TBI标志物。

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