■神经血管单元(NVU)的破坏,保持血脑屏障(BBB)的完整性,已被确定为脑血管和神经退行性疾病发展的关键机制。然而,对将NVU功能障碍与疾病联系起来的病理生理机制的理解是不完整的,和可靠的血液生物标志物来测量NVU功能障碍尚未建立。本系统综述和荟萃分析旨在确定与大血管疾病中BBB功能障碍相关的生物标志物。小血管病(SVD)和血管性认知障碍(VCD)。
■在PubMed进行了文献检索,EMBASE,Scopus和PsychINFO在2023年11月20日之前发布,以确定与血管病理学障碍中NVU功能障碍相关的血液生物标志物。包括测定人血清或血浆中的一种或多种特异性标志物的研究。使用纽卡斯尔-渥太华质量评估量表评估研究质量。使用随机效应模型汇集效应并检查方法异质性。
■本综述共纳入112项研究。如果研究数字允许,使用VCD(1项生物标志物;5项研究)和脑血管疾病的随机效应荟萃分析分析生物标志物,包括卒中和SVD(9项生物标志物;29项研究),其余所有生物标志物(n=17项生物标志物;78项研究)均通过定性分析进行检查.荟萃分析的结果表明,脑脊液/血清白蛋白商(Q-Alb)可靠地将VCD患者与健康对照区分开(MD=2.77;95%CI=1.97-3.57;p<0.0001),而通常测量的内皮功能障碍的生物标志物(VEGF,VCAM-1,ICAM-1,vWF和E-选择素)和神经元损伤(NfL)在血管病变中显着升高。非荟萃分析的生物标志物的定性评估显示NSE,NFL,vWF,ICAM-1,VCAM-1,脂质运载蛋白-2,MMP-2和MMP-9水平在VCD中上调,尽管这些发现并未得到一致的重复.
■本综述确定了NVU功能障碍的几种有希望的生物标志物,需要进一步验证。代表多种病理生理途径的一组生物标志物可以在区分VCD的可能疾病机制方面提供更大的辨别能力。
UNASSIGNED: The disruption of the neurovascular unit (NVU), which maintains the integrity of the blood brain barrier (BBB), has been identified as a critical mechanism in the development of cerebrovascular and neurodegenerative disorders. However, the understanding of the pathophysiological mechanisms linking NVU dysfunction to the disorders is incomplete, and reliable blood biomarkers to measure NVU dysfunction are yet to be established. This systematic review and meta-analysis aimed to identify biomarkers associated with BBB dysfunction in large vessel disease, small vessel disease (SVD) and vascular cognitive disorders (VCD).
UNASSIGNED: A literature search was conducted in PubMed, EMBASE, Scopus and PsychINFO to identify blood biomarkers related to dysfunction of the NVU in disorders with vascular pathologies published until 20 November 2023. Studies that assayed one or more specific markers in human serum or plasma were included. Quality of studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Effects were pooled and methodological heterogeneity examined using the random effects model.
UNASSIGNED: A total of 112 studies were included in this review. Where study numbers allowed, biomarkers were analysed using random effect meta-analysis for VCD (1 biomarker; 5 studies) and cerebrovascular disorders, including stroke and SVD (9 biomarkers; 29 studies) while all remaining biomarkers (n = 17 biomarkers; 78 studies) were examined through qualitative analysis. Results of the meta-analysis revealed that cerebrospinal fluid/serum albumin quotient (Q-Alb) reliably differentiates VCD patients from healthy controls (MD = 2.77; 95 % CI = 1.97-3.57; p < 0.0001) while commonly measured biomarkers of endothelial dysfunction (VEGF, VCAM-1, ICAM-1, vWF and E-selectin) and neuronal injury (NfL) were significantly elevated in vascular pathologies. A qualitative assessment of non-meta-analysed biomarkers revealed NSE, NfL, vWF, ICAM-1, VCAM-1, lipocalin-2, MMP-2 and MMP-9 levels to be upregulated in VCD, although these findings were not consistently replicated.
UNASSIGNED: This review identifies several promising biomarkers of NVU dysfunction which require further validation. A panel of biomarkers representing multiple pathophysiological pathways may offer greater discriminative power in distinguishing possible disease mechanisms of VCD.