Pujol-Calderón Fani, Portelius Erik, Zetterberg Henrik, Blennow Kaj, Rosengren Lars E, Höglund Kina
Department of Psychiatry & Neurochemistry, University of Gothenburg, Sweden.
Department of Psychiatry & Neurochemistry, University of Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Neurosci Lett. 2019 Apr 17;698:58-63. doi: 10.1016/j.neulet.2018.12.042. Epub 2018 Dec 29.
Neurofilament light (NFL) is a well-validated biomarker for neuronal injury and neurodegeneration. Increased cerebrospinal fluid (CSF) levels have been shown after stroke, as well as in patients with a broad range of neurodegenerative and neuroinflammatory diseases. Neurofilament heavy (NFH) belongs to the same family of structural proteins but it is less extensively studied. The potential of phosphorylated NFH (pNFH) as a stroke biomarker and for the prediction of clinical outcome is unknown. In this study, we aimed to examine the temporal pattern of NFL and pNFH concentrations in serum and CSF after acute ischemic stroke.
A quantitative Enzyme-Linked ImmunoSorbent Assay (ELISA) for pNFH was developed and tested on CSF and serum samples. NFL and pNFH were analysed in serum and CSF of acute ischemic stroke patients, who were followed over time (Day 0-1, Day 2-3, Day 7-9, three weeks, and 3-5 months after stroke).
NFL and pNFH concentrations in serum and CSF increased after stroke, peaked during the 3rd week, and then decreased back to almost baseline levels at 3-5 months. CSF-NFL and serum-NFL correlated to the outcome measured by Barthel Index after 3-5 months, whilst no such association was seen for pNFH.
These findings suggest that NFL and pNFH in both CSF and serum reflect the temporal pattern of the post ischemic axonal injury and that this process does not seem to progress after 3-5 months.
NFL and pNFH in CSF and serum are promising biomarkers for axonal injury following stroke. Further studies in larger populations are needed to fully understand the progression of the neuronal damage after acute ischemic stroke and to evaluate if these biomarkers can provide additive information and how they relate to outcome.
神经丝轻链(NFL)是一种经过充分验证的神经元损伤和神经退行性变生物标志物。中风后以及患有多种神经退行性和神经炎症性疾病的患者脑脊液(CSF)水平均会升高。神经丝重链(NFH)属于同一结构蛋白家族,但对其研究较少。磷酸化神经丝重链(pNFH)作为中风生物标志物及预测临床结局的潜力尚不清楚。在本研究中,我们旨在研究急性缺血性中风后血清和脑脊液中NFL和pNFH浓度的时间变化模式。
开发了一种用于pNFH的定量酶联免疫吸附测定(ELISA),并在脑脊液和血清样本上进行测试。对急性缺血性中风患者的血清和脑脊液进行NFL和pNFH分析,并对其进行随访(中风后第0 - 1天、第2 - 3天、第7 - 9天、三周以及3 - 5个月)。
中风后血清和脑脊液中NFL和pNFH浓度升高,在第3周达到峰值,然后在3 - 5个月时降至几乎基线水平。3 - 5个月后,脑脊液NFL和血清NFL与Barthel指数测量的结局相关,而pNFH未观察到这种关联。
这些发现表明,脑脊液和血清中的NFL和pNFH反映了缺血后轴突损伤的时间变化模式,并且这一过程在3 - 5个月后似乎不再进展。
脑脊液和血清中的NFL和pNFH是中风后轴突损伤有前景的生物标志物。需要在更大规模人群中进行进一步研究,以充分了解急性缺血性中风后神经元损伤的进展情况,并评估这些生物标志物是否能提供附加信息以及它们与结局的关系。