Abstract | BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH: Acute and chronic EAE models were induced in susceptible mice and 2AG-treatment was applied for 14 days from day of disease induction. KEY RESULTS: 2AG-treatment ameliorated acute phase of disease with delay of disease onset in both EAE models and reduced disease mortality and long-term (70 days post-induction) clinical disability in chronic EAE. Reduced axonal pathology in the chronic EAE- (p<0.0001) and increased activation and ramification of microglia in the 2AG-treated acute EAE- (p<0.05) model were noticed. The latter was accompanied by a 2- to 4-fold increase of the M2-macrophages in the perivascular infiltrations (p<0.001) of the 2AG-treated animals in the acute (day 22), although not the chronic (day 70), EAE model. Expression of cannabinoid receptors 1 (CB1R) and 2 (CB2R) was increased in 2AG-treated animals of acute EAE vs. controls (p<0.05). In addition, ex vivo viability assays exhibited reduced proliferation of activated lymph node cells when extracted from 2AG-treated EAE animals, whereas a dose-dependent response of activated lymphocytes to 2AG-treatment in vitro was noticed. CONCLUSION AND IMPLICATIONS: Our data indicate for the first time that 2AG treatment may provide direct (via CBRs) and immune (via M2 macrophages) mediated neuroprotection in EAE.
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Authors | Athanasios Lourbopoulos, Nikolaos Grigoriadis, Roza Lagoudaki, Olga Touloumi, Eleni Polyzoidou, Ioannis Mavromatis, Nikolaos Tascos, Aviva Breuer, Haim Ovadia, Dimitris Karussis, Ester Shohami, Raphael Mechoulam, Constantina Simeonidou |
Journal | Brain research
(Brain Res)
Vol. 1390
Pg. 126-41
(May 16 2011)
ISSN: 1872-6240 [Electronic] Netherlands |
PMID | 21406188
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Elsevier B.V. All rights reserved. |
Chemical References |
- Arachidonic Acids
- Endocannabinoids
- Glycerides
- glyceryl 2-arachidonate
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Topics |
- Acute Disease
- Animals
- Arachidonic Acids
(therapeutic use)
- Chronic Disease
- Disease Models, Animal
- Encephalomyelitis, Autoimmune, Experimental
(drug therapy, pathology)
- Endocannabinoids
- Female
- Glycerides
(therapeutic use)
- Mice
- Mice, Inbred C57BL
- Random Allocation
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