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Nafamostat mesilate improves function recovery after stroke by inhibiting neuroinflammation in rats.
- Source :
-
Brain, behavior, and immunity [Brain Behav Immun] 2016 Aug; Vol. 56, pp. 230-45. Date of Electronic Publication: 2016 Mar 24. - Publication Year :
- 2016
-
Abstract
- Inflammation plays an important role in stroke pathology, making it a promising target for stroke intervention. Nafamostat mesilate (NM), a wide-spectrum serine protease inhibitor, is commonly used for treating inflammatory diseases, such as pancreatitis. However, its effect on neuroinflammation after stroke was unknown. Hence, the effects of NM on the inflammatory response post stroke were characterized. After transient middle cerebral artery occlusion (tMCAO) in rats, NM reduced the infarct size, improved behavioral functions, decreased the expression of proinflammatory mediators (TNF-α, IL-1β, iNOS and COX-2) in a time-dependent manner and promoted the expression of different anti-inflammatory factors (CD206, TGF-β, IL-10 and IL-4) at different time points. Furthermore, NM could inhibit the expression of proinflammatory mediators and promote anti-inflammatory mediators expression in rat primary microglia following exposure to thrombin combined with oxygen-glucose deprivation (OGD). The immune-modulatory effect of NM might be partly due to its inhibition of the NF-κB signaling pathway and inflammasome activation after tMCAO. In addition, NM significantly inhibited the infiltration of macrophage, neutrophil and T lymphocytes, which was partly mediated by the inhibition of monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Taken together, our results indicated that NM can provide long-term protection of the brain against tMCAO by modulating a broad components of the inflammatory response.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Benzamidines
Disease Models, Animal
Guanidines administration & dosage
Inflammasomes drug effects
Male
Microglia drug effects
NF-kappa B drug effects
NLR Family, Pyrin Domain-Containing 3 Protein drug effects
Rats
Rats, Sprague-Dawley
Serine Proteinase Inhibitors administration & dosage
Thrombin drug effects
Behavior, Animal drug effects
Guanidines pharmacology
Infarction, Middle Cerebral Artery drug therapy
Inflammation drug therapy
Recovery of Function drug effects
Serine Proteinase Inhibitors pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2139
- Volume :
- 56
- Database :
- MEDLINE
- Journal :
- Brain, behavior, and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 27033633
- Full Text :
- https://doi.org/10.1016/j.bbi.2016.03.019