Platelet Inhibition by Low-Dose Acetylsalicylic Acid Reduces Neuroinflammation in an Animal Model of Multiple Sclerosis

• Published in: International journal of molecular sciences 2021-09, Vol.22 (18), p.9915
• Main Authors: Vogelsang, Anna, Eichler, Susann, Huntemann, Niklas, Masanneck, Lars, Böhnlein, Hannes, Schüngel, Lisa, Willison, Alice, Loser, Karin, Nieswandt, Bernhard, Kehrel, Beate E, Zarbock, Alexander, Göbel, Kerstin, Meuth, Sven G
• Format: Article
• Language: English
• Subjects: Acetylsalicylic acid; Adaptive immunity; Animal models; Animals; Aspirin; Aspirin - administration & dosage; Aspirin - pharmacology; Aspirin - therapeutic use; Blood Platelets - drug effects; Blood Platelets - pathology; Brain - pathology; CD4 antigen; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Central nervous system; Demyelination; Disease control; Disease Models, Animal; Disease prevention; Dose-Response Relationship, Drug; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - pathology; Etiology; Experimental allergic encephalomyelitis; experimental autoimmune encephalomyelitis; Flow cytometry; Glycoprotein VI; Heart attacks; Immune system; Inflammation; Inflammation - immunology; Inflammation - pathology; Investigations; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred C57BL; Multiple sclerosis; Multiple Sclerosis - blood; Multiple Sclerosis - immunology; Multiple Sclerosis - pathology; Oral administration; Plasma; Plasma levels; Platelet Aggregation Inhibitors - pharmacology; Platelet factor 4; platelets; Signs and symptoms; thromboxane; Thromboxane A2; Thromboxane A2 - biosynthesis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.