Contributions
Abstract: P940
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Experimental models
Background: Cannabidiol (CBD), non-psychoactive cannabinoid, has been reported to bind cannabinoid receptors (CB1-CB2) with weak affinity, although its mechanisms of action are not clear. Previous results showed an improvement in clinical symptoms in adoptively transferred EAE (at-EAE) treated with CBD. This model avoids interferences of inflamed sites with encephalitogenic cell circulation and allows a better delineation of the effector phase of the disease.
Objectives: To analyze CBD in adoptively transferred EAE and to elucidate its mechanisms of action in vitro.
Methods: After at-EAE induction, clinical signs were evaluated in at-EAE+vehicle and at-EAE+CBD 50mg/kg/d. In vitro, expression of CB1, CB2 and GPR55 receptors was determined by confocal microscopy. Viability was studied by MTT assay in spleen reactive cells treated with CBD and/or CB1 or CB2 antagonists or GPR55 ligand (SR1, SR2 or lysophosphatidylinositol (LPI) respectively). Reactive species of oxygen (ROS) were determined by flow cytometry after pre-incubation with CBD. MRI of the brain was carried out at 7T.
Results: CB1, CB2 and GPR55 receptors were present in the encephalitogenic spleen cells. CBD culture decreased viability of these cells and this was not restored by pre-incubation with SR1, SR2 or LPI; furthermore, CBD treatment significantly elevated the level of total cellular ROS. Reduction in clinical signs correlated with a significant decrease of apparent diffusion coefficient values in the brain subiculum after CBD treatment.
Conclusions: Clinical signs and MRI findings after CBD treatment correlated with a reduced recruitment of inflammatory cells into the CNS. The decrease in infiltrating cells could be due to the diminished viability of encephalitogenic spleen cells found in vitro with CBD treatment, an effect related to ROS increase. The viability reduction of encephalitogenic cells, independent of CB1-CB2 and GPR55 receptors, may be one of the mechanisms through which this compound exerts its therapeutic action.
Disclosure: - Coral González García: nothing to disclosure
- Antonio García-Merino: has received compensation for travel expenses, speaking honoraria and consultation fees from Bayer, Merck, Teva, Biogen Idec, Novartis, Roche, Almirall, Sanofi-Aventis and Genzyme
- Lucía Campos Ruíz: nothing to disclosure
- Irene Moreno Torres: nothing to disclosure
- Ruth García Hernández: nothing to disclosure
- María José Coronado Albí: nothing to disclosure
- Arantxa García Grande: nothing to disclosure
- Luis Rodríguez Esparragoza: nothing to disclosure
- Antonio Sánchez López: nothing to disclosure
Abstract: P940
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Experimental models
Background: Cannabidiol (CBD), non-psychoactive cannabinoid, has been reported to bind cannabinoid receptors (CB1-CB2) with weak affinity, although its mechanisms of action are not clear. Previous results showed an improvement in clinical symptoms in adoptively transferred EAE (at-EAE) treated with CBD. This model avoids interferences of inflamed sites with encephalitogenic cell circulation and allows a better delineation of the effector phase of the disease.
Objectives: To analyze CBD in adoptively transferred EAE and to elucidate its mechanisms of action in vitro.
Methods: After at-EAE induction, clinical signs were evaluated in at-EAE+vehicle and at-EAE+CBD 50mg/kg/d. In vitro, expression of CB1, CB2 and GPR55 receptors was determined by confocal microscopy. Viability was studied by MTT assay in spleen reactive cells treated with CBD and/or CB1 or CB2 antagonists or GPR55 ligand (SR1, SR2 or lysophosphatidylinositol (LPI) respectively). Reactive species of oxygen (ROS) were determined by flow cytometry after pre-incubation with CBD. MRI of the brain was carried out at 7T.
Results: CB1, CB2 and GPR55 receptors were present in the encephalitogenic spleen cells. CBD culture decreased viability of these cells and this was not restored by pre-incubation with SR1, SR2 or LPI; furthermore, CBD treatment significantly elevated the level of total cellular ROS. Reduction in clinical signs correlated with a significant decrease of apparent diffusion coefficient values in the brain subiculum after CBD treatment.
Conclusions: Clinical signs and MRI findings after CBD treatment correlated with a reduced recruitment of inflammatory cells into the CNS. The decrease in infiltrating cells could be due to the diminished viability of encephalitogenic spleen cells found in vitro with CBD treatment, an effect related to ROS increase. The viability reduction of encephalitogenic cells, independent of CB1-CB2 and GPR55 receptors, may be one of the mechanisms through which this compound exerts its therapeutic action.
Disclosure: - Coral González García: nothing to disclosure
- Antonio García-Merino: has received compensation for travel expenses, speaking honoraria and consultation fees from Bayer, Merck, Teva, Biogen Idec, Novartis, Roche, Almirall, Sanofi-Aventis and Genzyme
- Lucía Campos Ruíz: nothing to disclosure
- Irene Moreno Torres: nothing to disclosure
- Ruth García Hernández: nothing to disclosure
- María José Coronado Albí: nothing to disclosure
- Arantxa García Grande: nothing to disclosure
- Luis Rodríguez Esparragoza: nothing to disclosure
- Antonio Sánchez López: nothing to disclosure