Back to Search
Start Over
Selegiline Protects Against Lipopolysaccharide (LPS)–Induced Impairment of the Blood–Brain Barrier Through Regulating the NF-κB/MLCK/p-MLC Signaling Pathway.
- Source :
-
Neurotoxicity Research . Feb2022, Vol. 40 Issue 1, p267-275. 9p. - Publication Year :
- 2022
-
Abstract
- Disruption of the blood–brain barrier (BBB) is an important hallmark of sepsis-associated encephalopathy (SAE). Selegiline, a selective and irreversible inhibitor of monoamine oxidase type B, has been applied for the treatment of nervous disorders. In this study, we aimed to investigate whether selegiline has a protective capacity in the impairment of the BBB in both in vivo and in vitro experiments. In a sepsis mouse model, administration of selegiline ameliorated lipopolysaccharide (LPS)–induced impairment of BBB integrity. Additionally, treatment with selegiline increased the expression of the tight junction protein junctional adhesion molecule A (JAM-A) against LPS. Also, we found that selegiline inhibited the production of the proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β. In an in vitro experimental model, bEnd.3 brain endothelial cells were exposed to LPS. Results indicate that stimulation with LPS significantly increased the permeability of bEnd.3 cells and reduced the expression of JAM-A, both of which were rescued by treatment with selegiline. Additionally, selegiline prevented the activation of the NF-κB/MLCK/p-MLC signaling pathway in LPS-challenged bEnd.3 cells. These results indicate that selegiline exerted a protective effect on BBB dysfunction, which might be attributed to the inhibition of the NF-κB/MLCK/p-MLC signaling pathway. These findings provide a basis for further research into the neuroprotective mechanism of selegiline. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10298428
- Volume :
- 40
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Neurotoxicity Research
- Publication Type :
- Academic Journal
- Accession number :
- 154816790
- Full Text :
- https://doi.org/10.1007/s12640-021-00448-5