Department of Neurology with Institute of Translational Neurology, University Hospital Münster, 48149 Münster, Germany.
Department of Neurology, University Hospital Düsseldorf, 40225 Düsseldorf, Germany.
Int J Mol Sci. 2021 Sep 14;22(18):9915. doi: 10.3390/ijms22189915.
Aside from the established immune-mediated etiology of multiple sclerosis (MS), compelling evidence implicates platelets as important players in disease pathogenesis. Specifically, numerous studies have highlighted that activated platelets promote the central nervous system (CNS)-directed adaptive immune response early in the disease course. Platelets, therefore, present a novel opportunity for modulating the neuroinflammatory process that characterizes MS. We hypothesized that the well-known antiplatelet agent acetylsalicylic acid (ASA) could inhibit neuroinflammation by affecting platelets if applied at low-dose and investigated its effect during experimental autoimmune encephalomyelitis (EAE) as a model to study MS. We found that oral administration of low-dose ASA alleviates symptoms of EAE accompanied by reduced inflammatory infiltrates and less extensive demyelination. Remarkably, the percentage of CNS-infiltrated CD4 T cells, the major drivers of neuroinflammation, was decreased to 40.98 ± 3.28% in ASA-treated mice compared to 56.11 ± 1.46% in control animals at the disease maximum as revealed by flow cytometry. More interestingly, plasma levels of thromboxane A were decreased, while concentrations of platelet factor 4 and glycoprotein VI were not affected by low-dose ASA treatment. Overall, we demonstrate that low-dose ASA could ameliorate the platelet-dependent neuroinflammatory response in vivo, thus indicating a potential treatment approach for MS.
除了多发性硬化症（MS）已确立的免疫介导病因外，大量证据表明血小板在疾病发病机制中起着重要作用。具体来说，许多研究强调了活化的血小板促进了疾病早期中枢神经系统（CNS）定向的适应性免疫反应。因此，血小板为调节 MS 特征的神经炎症过程提供了一个新的机会。我们假设，如果在低剂量下应用，众所周知的抗血小板药物乙酰水杨酸（ASA）可以通过影响血小板来抑制神经炎症，并在实验性自身免疫性脑脊髓炎（EAE）中研究其作为 MS 模型的作用。我们发现，低剂量 ASA 的口服给药可缓解 EAE 的症状，同时减少炎症浸润和脱髓鞘。值得注意的是，流式细胞术显示，与对照组相比，ASA 治疗组小鼠中枢神经系统浸润的 CD4 T 细胞（神经炎症的主要驱动因素）的百分比降低至 40.98±3.28%，而在疾病高峰期，对照组为 56.11±1.46%。更有趣的是，低剂量 ASA 治疗不影响血浆血栓素 A 的水平，而血小板因子 4 和糖蛋白 VI 的浓度不受影响。总的来说，我们证明低剂量 ASA 可以改善体内依赖血小板的神经炎症反应，从而为 MS 提供了一种潜在的治疗方法。
