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死后脑脊液中的髓鞘碱性蛋白和神经丝 H 作为致命性创伤性脑损伤的替代标志物。

Myelin basic protein and neurofilament H in postmortem cerebrospinal fluid as surrogate markers of fatal traumatic brain injury.

机构信息

Institute of Forensic Medicine, University of Wuerzburg, Versbacher Str. 3, 97078, Wuerzburg, Germany.

Institute of Biochemistry and Molecular Biology I, Biozentrum - Am Hubland, 97074, Wuerzburg, Germany.

出版信息

Int J Legal Med. 2021 Jul;135(4):1525-1535. doi: 10.1007/s00414-021-02606-y. Epub 2021 Apr 24.

Abstract

The aim of this study was to investigate if the biomarkers myelin basic protein (MBP) and neurofilament-H (NF-H) yielded informative value in forensic diagnostics when examining cadaveric cerebrospinal fluid (CSF) biochemically via an enzyme-linked immunosorbent assay (ELISA) and comparing the corresponding brain tissue in fatal traumatic brain injury (TBI) autopsy cases by immunocytochemistry versus immunohistochemistry. In 21 trauma and 19 control cases, CSF was collected semi-sterile after suboccipital puncture and brain specimens after preparation. The CSF MBP (p = 0.006) and NF-H (p = 0.0002) levels after TBI were significantly higher than those in cardiovascular controls. Immunohistochemical staining against MBP and against NF-H was performed on cortical and subcortical samples from also biochemically investigated cases (5 TBI cases/5 controls). Compared to the controls, the TBI cases showed a visually reduced staining reaction against MBP or repeatedly ruptured neurofilaments against NF-H. Immunocytochemical tests showed MBP-positive phagocytizing macrophages in CSF with a survival time of > 24 h. In addition, numerous TMEM119-positive microglia could be detected with different degrees of staining intensity in the CSF of trauma cases. As a result, we were able to document that elevated levels of MBP and NF-H in the CSF should be considered as useful neuroinjury biomarkers of traumatic brain injury.

摘要

本研究旨在通过酶联免疫吸附测定法(ELISA)对半无菌性枕下入路穿刺获取的尸检脑脊液(CSF)进行生化检测,并与免疫细胞化学和免疫组织化学对比检测外伤性脑损伤(TBI)尸检标本,从而探讨髓鞘碱性蛋白(MBP)和神经丝-H(NF-H)这两种生物标志物在法医诊断中的应用价值。在 21 例创伤和 19 例对照病例中,在准备好脑标本后,通过枕下入路穿刺收集半无菌性 CSF。TBI 后 CSF 中的 MBP(p=0.006)和 NF-H(p=0.0002)水平明显高于心血管对照。对来自生物化学检测病例的皮质和皮质下样本(5 例 TBI 病例/5 例对照)进行 MBP 和 NF-H 的免疫组织化学染色。与对照组相比,TBI 病例的 MBP 或 NF-H 染色反应明显减弱或反复出现神经丝断裂。免疫细胞化学试验显示,存活时间超过 24 小时的 CSF 中存在 MBP 阳性的吞噬性巨噬细胞。此外,在创伤病例的 CSF 中,还可以检测到 TMEM119 阳性的小胶质细胞,其染色强度存在不同程度的差异。结果表明,CSF 中 MBP 和 NF-H 水平升高可作为外伤性脑损伤的有用神经损伤生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/add8/8205912/cf608eadb9f5/414_2021_2606_Fig1_HTML.jpg

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