Inhaled nitric oxide suppresses neuroinflammation in experimental ischemic stroke

Autor: 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
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Neuroinflammation, Vol 20, Iss 1, Pp 1-15 (2023)
Druh dokumentu: article
ISSN: 1742-2094
DOI: 10.1186/s12974-023-02988-3
Popis: 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.
Databáze: Directory of Open Access Journals
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