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子痫前期的脑生物标志物与血脑屏障完整性。

Cerebral Biomarkers and Blood-Brain Barrier Integrity in Preeclampsia.

机构信息

Department of Women's and Children's Health, Uppsala University, 75185 Uppsala, Sweden.

Vascular Physiology Laboratory, Department of Basic Sciences, Faculty of Sciences, University of Bío-Bío, Chillán 3810178, Chile.

出版信息

Cells. 2022 Feb 24;11(5):789. doi: 10.3390/cells11050789.

Abstract

Cerebral complications in preeclampsia contribute substantially to maternal mortality and morbidity. There is a lack of reliable and accessible predictors for preeclampsia-related cerebral complications. In this study, plasma from women with preeclampsia (n = 28), women with normal pregnancies (n = 28) and non-pregnant women (n = 16) was analyzed for concentrations of the cerebral biomarkers neurofilament light (NfL), tau, neuron-specific enolase (NSE) and S100B. Then, an in vitro blood−brain barrier (BBB) model, based on the human cerebral microvascular endothelial cell line (hCMEC/D3), was employed to assess the effect of plasma from the three study groups. Transendothelial electrical resistance (TEER) was used as an estimation of BBB integrity. NfL and tau are proteins expressed in axons, NSE in neurons and S100B in glial cells and are used as biomarkers for neurological injury in other diseases such as dementia, traumatic brain injury and hypoxic brain injury. Plasma concentrations of NfL, tau, NSE and S100B were all higher in women with preeclampsia compared with women with normal pregnancies (8.85 vs. 5.25 ng/L, p < 0.001; 2.90 vs. 2.40 ng/L, p < 0.05; 3.50 vs. 2.37 µg/L, p < 0.001 and 0.08 vs. 0.05 µg/L, p < 0.01, respectively). Plasma concentrations of NfL were also higher in women with preeclampsia compared with non-pregnant women (p < 0.001). Higher plasma concentrations of the cerebral biomarker NfL were associated with decreased TEER (p = 0.002) in an in vitro model of the BBB, a finding which indicates that NfL could be a promising biomarker for BBB alterations in preeclampsia.

摘要

子痫前期的脑部并发症是导致产妇死亡和发病的主要原因。目前,子痫前期相关脑部并发症缺乏可靠且易于获取的预测指标。在这项研究中,分析了 28 例子痫前期妇女、28 例正常妊娠妇女和 16 例非妊娠妇女的血浆中神经丝轻链(NfL)、tau、神经元特异性烯醇化酶(NSE)和 S100B 的浓度。然后,采用基于人脑血管内皮细胞系(hCMEC/D3)的体外血脑屏障(BBB)模型来评估来自三组研究对象的血浆的作用。跨内皮电阻(TEER)被用作 BBB 完整性的估计。NfL 和 tau 是轴突中表达的蛋白质,NSE 是神经元中的蛋白质,S100B 是神经胶质细胞中的蛋白质,它们被用作痴呆、创伤性脑损伤和缺氧性脑损伤等其他疾病的神经损伤标志物。与正常妊娠妇女相比,子痫前期妇女的血浆 NfL、tau、NSE 和 S100B 浓度均升高(8.85 与 5.25ng/L,p<0.001;2.90 与 2.40ng/L,p<0.05;3.50 与 2.37μg/L,p<0.001 和 0.08 与 0.05μg/L,p<0.01)。与非妊娠妇女相比,子痫前期妇女的血浆 NfL 浓度也升高(p<0.001)。体外 BBB 模型中,较高的血浆脑生物标志物 NfL 浓度与 TEER 降低相关(p=0.002),这表明 NfL 可能是子痫前期 BBB 改变的有前途的标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/751d/8909006/675d3cea4a16/cells-11-00789-g001.jpg

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