title: Administration of 2-arachidonoylglycerol ameliorates both acute and chronic experimental autoimmune encephalomyelitis.
abstract: OBJECTIVE
  Experimental autoimmune encephalomyelitis (EAE) is a widely used model of multiple sclerosis (MS) and both conditions have been reported to exhibit reduced endocannabinoid activity. The purpose of this study was to address the effect of exogenously administered 2-arachidonoylglycerol (2AG), an endocannabinoid receptor ligand, on acute phase and chronic disability in EAE.
  
  
  METHODS
  Acute and chronic EAE models were induced in susceptible mice and 2AG-treatment was applied for 14 days from day of disease induction.
  
  
  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.
  
  
  CONCLUSIONS
  Our data indicate for the first time that 2AG treatment may provide direct (via CBRs) and immune (via M2 macrophages) mediated neuroprotection in EAE.
authors.affiliation: Laboratory of Experimental Neurology and Neuroimmunology, B' Department of Neurology, AHEPA University Hospital Aristotle University, Thessaloniki 54636, Macedonia, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Lourbopoulos
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Grigoriadis
authors.forename: Roza
authors.initials: R
authors.lastname: Lagoudaki
authors.forename: Olga
authors.initials: O
authors.lastname: Touloumi
authors.forename: Eleni
authors.initials: E
authors.lastname: Polyzoidou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Mavromatis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Tascos
authors.forename: Aviva
authors.initials: A
authors.lastname: Breuer
authors.forename: Haim
authors.initials: H
authors.lastname: Ovadia
authors.forename: Dimitris
authors.initials: D
authors.lastname: Karussis
authors.forename: Ester
authors.initials: E
authors.lastname: Shohami
authors.forename: Raphael
authors.initials: R
authors.lastname: Mechoulam
authors.forename: Constantina
authors.initials: C
authors.lastname: Simeonidou
mesh_terms: D000208:Acute Disease; D000818:Animals; D001095:Arachidonic Acids / Q000627:therapeutic use*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology; D063388:Endocannabinoids; D005260:Female; D005989:Glycerides / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; C094503:glyceryl 2-arachidonate