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|Title:||A cannabinoid agonist interferes with the progression of a chronic model of multiple sclerosis by downregulating adhesion molecules|
|Authors:||Mestre, L., Docagne, F., Correa, F., Loría, F., Hernangómez, M., Borrell, Jose, Guaza, Carmen|
|Abstract:||Adhesion molecules are critical players in the regulation of transmigration of blood leukocytes across the blood-brain barrier in multiple sclerosis (MS). Cannabinoids (CBs) are potential therapeutic agents in the treatment of MS, but the mechanisms involved are only partially known. Using a viral model of MS we observed that the cannabinoid agonist WIN55,212-2 administered at the time of virus infection suppresses intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in brain endothelium, together with a reduction in perivascular CD4+ T lymphocytes infiltrates and microglial responses. WIN55,212-2 also interferes with later progression of the disease by reducing symptomatology and neuroinflammation. In vitro data from brain endothelial cell cultures, provide the first evidence of a role of peroxisome proliferator-activated receptors gamma (PPARγ) in WIN55,212-2-induced downregulation of VCAM-1. This study highlights that inhibition of brain adhesion molecules by WIN55,212-2 might underline its therapeutic effects in MS models by targeting PPAR-γ receptors. © 2008 Elsevier Inc. All rights reserved.|
|Citation:||Molecular and Cellular Neurosciences 40: 258- 266 (2009)|
|Appears in Collections:||(IC) Artículos|
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