脑源性神经营养因子、神经丝轻链蛋白和胶质纤维酸性蛋白在与多发性硬化症相关疲劳的人群中不会因有氧训练而发生变化——一项随机对照试验的二次分析
Brain-derived neurotrophic factor, neurofilament light and glial fibrillary acidic protein do not change in response to aerobic training in people with MS-related fatigue - a secondary analysis of a randomized controlled trial.
作者信息
Gravesteijn Arianne S, Beckerman Heleen, Willemse Eline Aj, Hulst Hanneke E, de Jong Brigit A, Teunissen Charlotte E, de Groot Vincent
机构信息
MS Center Amsterdam, Rehabilitation Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, The Netherlands, PO Box 7057, 1007 MB Amsterdam.
MS Center Amsterdam, Clinical Chemistry, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, The Netherlands, PO Box 7057, 1007 MB Amsterdam; Neurology Clinic and Policlinic, Departments of Head, Spine and Neuromedicine, Biomedicine and Clinical Research, Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), University Hospital Basel, University of Basel, Spitalstrasse 2, CH-4031 Basel, Switzerland.
出版信息
Mult Scler Relat Disord. 2023 Feb;70:104489. doi: 10.1016/j.msard.2022.104489. Epub 2022 Dec 28.
BACKGROUND
Neuroinflammation and neurodegeneration are pathological hallmarks of multiple sclerosis (MS). Brain-derived neurotrophic factor (BDNF), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) are blood-based biomarkers for neurogenesis, axonal damage and astrocyte reactivity, respectively. We hypothesize that exercise has a neuroprotective effect on MS reflected by normalization of BDNF, NfL and GFAP levels.
OBJECTIVES
To investigate the neuroprotective effect of aerobic training (AT) compared to a control intervention on blood-based biomarkers (i.e. BDNF, NfL, GFAP) in people with MS (pwMS).
METHODS
In the TREFAMS-AT (Treating Fatigue in Multiple Sclerosis - Aerobic Training) study, 89 pwMS were randomly allocated to either a 16-week AT intervention or a control intervention (3 visits to a MS nurse). In this secondary analysis, blood-based biomarker concentrations were measured in 55 patients using Simoa technology. Changes in pre- and post-intervention concentrations were compared and between-group differences were assessed using analysis of covariance (ANCOVA). Confounding effects of age, sex, MS-related disability assessed using the Expanded Disability Status Scale (EDSS), MS duration, use of disease-modifying medication, and Body Mass Index were considered.
RESULTS
Blood samples were available for 30 AT and 25 control group participants (mean age 45.6 years, 71% female, median disease duration 8 years, median EDSS score 2.5). Within-group changes in both study groups were small and non-significant, with the exception of BDNF in the control group (median (interquartile range) -2.1 (-4.7; 0)). No between-group differences were found for any biomarker: BDNF (β = 0.11, 95%CI (-3.78 to 4.00)), NfL (β = -0.04, 95%CI (-0.26 to 0.18)), and GFAP (β = -0.01, 95%CI (-0.16 to 0.15)), adjusted for confounders.
CONCLUSION
Aerobic exercise therapy did not result in statistically significant changes in the tested neuro-specific blood-based biomarkers in people with MS.
TRIAL REGISTRATION
this study is registered under number ISRCTN69520623 (https://www.isrctn.com/ISRCTN695206).
背景
神经炎症和神经退行性变是多发性硬化症（MS）的病理特征。脑源性神经营养因子（BDNF）、神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP）分别是神经发生、轴突损伤和星形胶质细胞反应性的血液生物标志物。我们假设运动对MS具有神经保护作用，这可通过BDNF、NfL和GFAP水平的正常化来体现。
目的
研究有氧训练（AT）与对照干预相比，对多发性硬化症患者（pwMS）血液生物标志物（即BDNF、NfL、GFAP）的神经保护作用。
方法
在TREFAMS-AT（多发性硬化症疲劳治疗 - 有氧训练）研究中，89名pwMS被随机分配到16周的AT干预组或对照干预组（与MS护士进行3次问诊）。在本次二次分析中，使用单分子阵列（Simoa）技术测量了55名患者的血液生物标志物浓度。比较干预前后浓度的变化，并使用协方差分析（ANCOVA）评估组间差异。考虑了年龄、性别、使用扩展残疾状态量表（EDSS）评估的MS相关残疾、MS病程、疾病修饰药物的使用以及体重指数的混杂效应。
结果
有30名AT组参与者和25名对照组参与者的血液样本可供分析（平均年龄45.6岁，71%为女性，疾病持续时间中位数为8年，EDSS评分中位数为2.5）。除对照组的BDNF外，两个研究组内的变化均较小且无统计学意义（中位数（四分位间距）为 -2.1（-4.7；0））。在调整混杂因素后，任何生物标志物在组间均未发现差异：BDNF（β = 0.11，95%置信区间（-3.78至4.00））、NfL（β = -0.04，95%置信区间（-0.26至0.18））和GFAP（β = -0.01，95%置信区间（-0.16至0.15））。
结论
有氧运动疗法并未使MS患者测试的神经特异性血液生物标志物产生具有统计学意义的变化。
试验注册
本研究已在ISRCTN69520623（https://www.isrctn.com/ISRCTN695206）注册。
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