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Closed Access item 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
Issue Date:2009
Publisher:Academic Press
Citation:Molecular and Cellular Neurosciences 40: 258- 266 (2009)
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.
URI:http://hdl.handle.net/10261/59558
Identifiers:doi: 10.1016/j.mcn.2008.10.015
issn: 1044-7431
Appears in Collections:(IC) Artículos

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