Nielsen Helle H, Soares Catarina B, Høgedal Sofie S, Madsen Jonna S, Hansen Rikke B, Christensen Alex A, Madsen Charlotte, Clausen Bettina H, Frich Lars Henrik, Degn Matilda, Sibbersen Christian, Lambertsen Kate L
Department of Neurology, Odense University Hospital, Odense, Denmark.
Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Front Neurol. 2020 Jun 11;11:448. doi: 10.3389/fneur.2020.00448. eCollection 2020.
Ischemic stroke causes increased blood-brain barrier permeability and release of markers of axonal damage and inflammation. To investigate diagnostic and prognostic roles of neurofilament light chain (NF-L), we assessed levels of NF-L, S100B, interleukin-6 (IL-6), E-selectin, vascular endothelial growth factor-A (VEGF-A), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in patients with acute ischemic stroke or transient ischemic attack (TIA) and healthy controls. We studied neurofilament (NF) expression in 2 cases of human postmortem ischemic stroke, representing infarcts aged 3- to >7-days. In a prospective study, we measured plasma NF-L and inflammatory markers <8 h of symptom onset and at 72 h in acute ischemic stroke ( = 31), TIA ( = 9), and healthy controls ( = 29). We assessed whether NF-L, S100B, and IL-6 were associated with clinical severity on admission (Scandinavian Stroke Scale, SSS), diagnosis of ischemic stroke vs. TIA, and functional outcome at 3 months (modified Rankin Scale, mRS). NF expression increased in ischemic neurons and in the infarcted brain parenchyma after stroke. Plasma NF-L levels were higher in stroke patients than in TIA patients and healthy controls, but IL-6 levels were similar. Higher acute NF-L levels were associated with lower SSS scores at admission and higher mRS scores at 3 months. No correlation was observed between NF-L and S100B, NF-L and IL-6, nor between S100B or IL-6 and SSS or mRS. Compared to controls, stroke patients had significantly higher VEGF-A and VCAM-1 at <8 h that remained elevated at 72 h, with significantly higher VEGF-A at <8 h; ICAM-1 was significantly increased at <8 h, while S100B and E-selectin were unchanged. Plasma NF-L levels, but not IL-6 and S100B, were significant predictors of clinical severity on admission and functional outcome at 3 months. Plasma NF-L is a promising biomarker of functional outcome after ischemic stroke.
缺血性中风会导致血脑屏障通透性增加以及轴突损伤和炎症标志物的释放。为了研究神经丝轻链（NF-L）的诊断和预后作用，我们评估了急性缺血性中风或短暂性脑缺血发作（TIA）患者及健康对照者体内NF-L、S100B、白细胞介素-6（IL-6）、E-选择素、血管内皮生长因子-A（VEGF-A）、血管细胞黏附分子-1（VCAM-1）和细胞间黏附分子-1（ICAM-1）的水平。我们研究了2例人类死后缺血性中风病例中的神经丝（NF）表达情况，这些梗死灶的病程为3天至超过7天。在一项前瞻性研究中，我们测量了急性缺血性中风（n = 31）、TIA（n = 9）和健康对照者（n = 29）在症状发作后<8小时和72小时时的血浆NF-L及炎症标志物水平。我们评估了NF-L、S100B和IL-6是否与入院时的临床严重程度（斯堪的纳维亚卒中量表，SSS）、缺血性中风与TIA的诊断以及3个月时的功能结局（改良Rankin量表，mRS）相关。中风后，缺血神经元和梗死脑实质中的NF表达增加。中风患者的血浆NF-L水平高于TIA患者和健康对照者，但IL-6水平相似。急性NF-L水平较高与入院时较低的SSS评分以及3个月时较高的mRS评分相关。未观察到NF-L与S100B、NF-L与IL-6之间存在相关性，S100B或IL-6与SSS或mRS之间也无相关性。与对照组相比，中风患者在<8小时时VEGF-A和VCAM-1显著更高，在72小时时仍保持升高，其中<8小时时VEGF-A显著更高；ICAM-1在<8小时时显著增加，而S100B和E-选择素未发生变化。血浆NF-L水平而非IL-6和S100B水平与入院时的临床严重程度及3个月时的功能结局相关。血浆NF-L是缺血性中风后功能结局的一个有前景的生物标志物。
