Inhaled nitric oxide suppresses neuroinflammation in experimental ischemic stroke
Abstract Ischemic stroke is a major global health issue and characterized by acute vascular dysfunction and subsequent neuroinflammation. However, the relationship between these processes remains elusive. In the current study, we investigated whether alleviating vascular dysfunction by restoring vas...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-12-01
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| Series: | Journal of Neuroinflammation |
| Online Access: | https://doi.org/10.1186/s12974-023-02988-3 |
| _version_ | 1797388159183486976 |
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| author | Rebecca I. Sienel Uta Mamrak Janina Biller Stefan Roth Andreas Zellner Tipparat Parakaw Rayomand S. Khambata Arthur Liesz Christof Haffner Amrita Ahluwalia Burcu F. Seker Nikolaus Plesnila |
| author_facet | Rebecca I. Sienel Uta Mamrak Janina Biller Stefan Roth Andreas Zellner Tipparat Parakaw Rayomand S. Khambata Arthur Liesz Christof Haffner Amrita Ahluwalia Burcu F. Seker Nikolaus Plesnila |
| author_sort | Rebecca I. Sienel |
| collection | DOAJ |
| description | Abstract Ischemic stroke is a major global health issue and characterized by acute vascular dysfunction and subsequent neuroinflammation. However, the relationship between these processes remains elusive. In the current study, we investigated whether alleviating vascular dysfunction by restoring vascular nitric oxide (NO) reduces post-stroke inflammation. Mice were subjected to experimental stroke and received inhaled NO (iNO; 50 ppm) after reperfusion. iNO normalized vascular cyclic guanosine monophosphate (cGMP) levels, reduced the elevated expression of intercellular adhesion molecule-1 (ICAM-1), and returned leukocyte adhesion to baseline levels. Reduction of vascular pathology significantly reduced the inflammatory cytokines interleukin-1β (Il-1β), interleukin-6 (Il-6), and tumor necrosis factor-α (TNF-α), within the brain parenchyma. These findings suggest that vascular dysfunction is responsible for leukocyte adhesion and that these processes drive parenchymal inflammation. Reversing vascular dysfunction may therefore emerge as a novel approach to diminish neuroinflammation after ischemic stroke and possibly other ischemic disorders. |
| first_indexed | 2024-03-08T22:36:49Z |
| format | Article |
| id | doaj.art-cff1eeded54441de8fcfefccd3e1e390 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-03-08T22:36:49Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-cff1eeded54441de8fcfefccd3e1e3902023-12-17T12:25:22ZengBMCJournal of Neuroinflammation1742-20942023-12-0120111510.1186/s12974-023-02988-3Inhaled nitric oxide suppresses neuroinflammation in experimental ischemic strokeRebecca I. Sienel0Uta Mamrak1Janina Biller2Stefan Roth3Andreas Zellner4Tipparat Parakaw5Rayomand S. Khambata6Arthur Liesz7Christof Haffner8Amrita Ahluwalia9Burcu F. Seker10Nikolaus Plesnila11Institute for Stroke and Dementia Research, Klinikum der Universität München and Ludwig Maximilian University (LMU) MunichInstitute for Stroke and Dementia Research, Klinikum der Universität München and Ludwig Maximilian University (LMU) MunichInstitute for Stroke and Dementia Research, Klinikum der Universität München and Ludwig Maximilian University (LMU) MunichInstitute for Stroke and Dementia Research, Klinikum der Universität München and Ludwig Maximilian University (LMU) MunichInstitute for Stroke and Dementia Research, Klinikum der Universität München and Ludwig Maximilian University (LMU) MunichWilliam Harvey Research Institute, Barts & The London School of Medicine and Dentistry, Queen Mary University of LondonWilliam Harvey Research Institute, Barts & The London School of Medicine and Dentistry, Queen Mary University of LondonInstitute for Stroke and Dementia Research, Klinikum der Universität München and Ludwig Maximilian University (LMU) MunichInstitute for Stroke and Dementia Research, Klinikum der Universität München and Ludwig Maximilian University (LMU) MunichWilliam Harvey Research Institute, Barts & The London School of Medicine and Dentistry, Queen Mary University of LondonInstitute for Stroke and Dementia Research, Klinikum der Universität München and Ludwig Maximilian University (LMU) MunichInstitute for Stroke and Dementia Research, Klinikum der Universität München and Ludwig Maximilian University (LMU) MunichAbstract Ischemic stroke is a major global health issue and characterized by acute vascular dysfunction and subsequent neuroinflammation. However, the relationship between these processes remains elusive. In the current study, we investigated whether alleviating vascular dysfunction by restoring vascular nitric oxide (NO) reduces post-stroke inflammation. Mice were subjected to experimental stroke and received inhaled NO (iNO; 50 ppm) after reperfusion. iNO normalized vascular cyclic guanosine monophosphate (cGMP) levels, reduced the elevated expression of intercellular adhesion molecule-1 (ICAM-1), and returned leukocyte adhesion to baseline levels. Reduction of vascular pathology significantly reduced the inflammatory cytokines interleukin-1β (Il-1β), interleukin-6 (Il-6), and tumor necrosis factor-α (TNF-α), within the brain parenchyma. These findings suggest that vascular dysfunction is responsible for leukocyte adhesion and that these processes drive parenchymal inflammation. Reversing vascular dysfunction may therefore emerge as a novel approach to diminish neuroinflammation after ischemic stroke and possibly other ischemic disorders.https://doi.org/10.1186/s12974-023-02988-3 |
| spellingShingle | Rebecca I. Sienel Uta Mamrak Janina Biller Stefan Roth Andreas Zellner Tipparat Parakaw Rayomand S. Khambata Arthur Liesz Christof Haffner Amrita Ahluwalia Burcu F. Seker Nikolaus Plesnila Inhaled nitric oxide suppresses neuroinflammation in experimental ischemic stroke Journal of Neuroinflammation |
| title | Inhaled nitric oxide suppresses neuroinflammation in experimental ischemic stroke |
| title_full | Inhaled nitric oxide suppresses neuroinflammation in experimental ischemic stroke |
| title_fullStr | Inhaled nitric oxide suppresses neuroinflammation in experimental ischemic stroke |
| title_full_unstemmed | Inhaled nitric oxide suppresses neuroinflammation in experimental ischemic stroke |
| title_short | Inhaled nitric oxide suppresses neuroinflammation in experimental ischemic stroke |
| title_sort | inhaled nitric oxide suppresses neuroinflammation in experimental ischemic stroke |
| url | https://doi.org/10.1186/s12974-023-02988-3 |
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