Platelet Inhibition by Low-Dose Acetylsalicylic Acid Reduces Neuroinflammation in an Animal Model of Multiple Sclerosis
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 i...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/18/9915 |
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| author | Anna Vogelsang Susann Eichler Niklas Huntemann Lars Masanneck Hannes Böhnlein Lisa Schüngel Alice Willison Karin Loser Bernhard Nieswandt Beate E. Kehrel Alexander Zarbock Kerstin Göbel Sven G. Meuth |
| author_facet | Anna Vogelsang Susann Eichler Niklas Huntemann Lars Masanneck Hannes Böhnlein Lisa Schüngel Alice Willison Karin Loser Bernhard Nieswandt Beate E. Kehrel Alexander Zarbock Kerstin Göbel Sven G. Meuth |
| author_sort | Anna Vogelsang |
| collection | DOAJ |
| description | 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<sup>+</sup> 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<sub>2</sub> 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. |
| first_indexed | 2024-03-10T07:35:33Z |
| format | Article |
| id | doaj.art-33c080d5cc2040faa09ef97234ba9ac6 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:35:33Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-33c080d5cc2040faa09ef97234ba9ac62023-11-22T13:29:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012218991510.3390/ijms22189915Platelet Inhibition by Low-Dose Acetylsalicylic Acid Reduces Neuroinflammation in an Animal Model of Multiple SclerosisAnna Vogelsang0Susann Eichler1Niklas Huntemann2Lars Masanneck3Hannes Böhnlein4Lisa Schüngel5Alice Willison6Karin Loser7Bernhard Nieswandt8Beate E. Kehrel9Alexander Zarbock10Kerstin Göbel11Sven G. Meuth12Department of Neurology with Institute of Translational Neurology, University Hospital Münster, 48149 Münster, GermanyDepartment of Neurology with Institute of Translational Neurology, University Hospital Münster, 48149 Münster, GermanyDepartment of Neurology with Institute of Translational Neurology, University Hospital Münster, 48149 Münster, GermanyDepartment of Neurology with Institute of Translational Neurology, University Hospital Münster, 48149 Münster, GermanyDepartment of Neurology with Institute of Translational Neurology, University Hospital Münster, 48149 Münster, GermanyDepartment of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, 48149 Münster, GermanyThe Northern Foundation School, Newcastle-upon-Tyne University Hospitals, Newcastle-upon-Tyne NE15 8NY, UKDepartment of Human Medicine, Institute of Immunology, Carl von Ossietzky University Oldenburg, 26129 Oldenburg, GermanyRudolf Virchow Center, Research Center for Experimental Biomedicine, University of Würzburg, 97080 Würzburg, GermanyDepartment of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, 48149 Münster, GermanyDepartment of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, 48149 Münster, GermanyDepartment of Neurology with Institute of Translational Neurology, University Hospital Münster, 48149 Münster, GermanyDepartment of Neurology, University Hospital Düsseldorf, 40225 Düsseldorf, GermanyAside 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<sup>+</sup> 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<sub>2</sub> 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.https://www.mdpi.com/1422-0067/22/18/9915acetylsalicylic acidexperimental autoimmune encephalomyelitisplateletsmultiple sclerosisthromboxaneglycoprotein VI |
| spellingShingle | Anna Vogelsang Susann Eichler Niklas Huntemann Lars Masanneck Hannes Böhnlein Lisa Schüngel Alice Willison Karin Loser Bernhard Nieswandt Beate E. Kehrel Alexander Zarbock Kerstin Göbel Sven G. Meuth Platelet Inhibition by Low-Dose Acetylsalicylic Acid Reduces Neuroinflammation in an Animal Model of Multiple Sclerosis International Journal of Molecular Sciences acetylsalicylic acid experimental autoimmune encephalomyelitis platelets multiple sclerosis thromboxane glycoprotein VI |
| title | Platelet Inhibition by Low-Dose Acetylsalicylic Acid Reduces Neuroinflammation in an Animal Model of Multiple Sclerosis |
| title_full | Platelet Inhibition by Low-Dose Acetylsalicylic Acid Reduces Neuroinflammation in an Animal Model of Multiple Sclerosis |
| title_fullStr | Platelet Inhibition by Low-Dose Acetylsalicylic Acid Reduces Neuroinflammation in an Animal Model of Multiple Sclerosis |
| title_full_unstemmed | Platelet Inhibition by Low-Dose Acetylsalicylic Acid Reduces Neuroinflammation in an Animal Model of Multiple Sclerosis |
| title_short | Platelet Inhibition by Low-Dose Acetylsalicylic Acid Reduces Neuroinflammation in an Animal Model of Multiple Sclerosis |
| title_sort | platelet inhibition by low dose acetylsalicylic acid reduces neuroinflammation in an animal model of multiple sclerosis |
| topic | acetylsalicylic acid experimental autoimmune encephalomyelitis platelets multiple sclerosis thromboxane glycoprotein VI |
| url | https://www.mdpi.com/1422-0067/22/18/9915 |
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