title: Possible Anandamide and Palmitoylethanolamide involvement in human stroke.
abstract: BACKGROUND
  Endocannabinoids (eCBs) are ubiquitous lipid mediators that act on specific (CB1, CB2) and non-specific (TRPV1, PPAR) receptors. Despite many experimental animal studies proved eCB involvement in the pathogenesis of stroke, such evidence is still lacking in human patients. Our aim was to determine eCB peripheral levels in acute stroke patients and evaluate their relationship with clinical disability and stroke volume.
  
  
  METHODS
  A cohort of ten patients with a first acute (within six hours since symptoms onset) ischemic stroke and a group of eight age- and sex-matched normal subjects were included. Groups were also matched for metabolic profile. All subjects underwent a blood sample collection for anandamide (AEA), 2-arachidonoylglycerol (2-AG) and palmitoylethanolamide (PEA) measurement; blood sampling was repeated in patients on admission (T0), at 6 (T1) and 18 hours (T2) thereafter. Patients neurological impairment was assessed using NIHSS and Fugl-Meyer Scale arm subitem (FMSa); stroke volume was determined on 48 h follow-up brain CT scans. Blood samples were analyzed by liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry.
  
  
  RESULTS
  1)T0 AEA levels were significantly higher in stroke patients compared to controls. 2)A significant inverse correlation between T0 AEA levels and FMSa score was found. Moreover a positive correlation between T0 AEA levels and stroke volume were found in stroke patients. T0 PEA levels in stroke patients were not significantly different from the control group, but showed a significant correlation with the NIHSS scores. T0 2-AG levels were lower in stroke patients compared to controls, but such difference did not reach the significance threshold.
  
  
  CONCLUSIONS
  This is the first demonstration of elevated peripheral AEA levels in acute stroke patients. In agreement with previous murine studies, we found a significant relationship between AEA or PEA levels and neurological involvement, such that the greater the neurological impairment, the higher were these levels.
authors.affiliation: Department of Medical, Technological and Translational Sciences, Neurology Unit, University of Trieste, Strada di Fiume 447, 34100 Trieste (TS), Italy. marcello.naccarato@katamail.com
authors.forename: Marcello
authors.initials: M
authors.lastname: Naccarato
authors.forename: Daniela
authors.initials: D
authors.lastname: Pizzuti
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrosino
authors.forename: Marco
authors.initials: M
authors.lastname: Simonetto
authors.forename: Laura
authors.initials: L
authors.lastname: Ferigo
authors.forename: Fabio Chiodo
authors.initials: FC
authors.lastname: Grandi
authors.forename: Gilberto
authors.initials: G
authors.lastname: Pizzolato
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000577:Amides; D001095:Arachidonic Acids / Q000097:blood*; D063385:Cannabinoid Receptor Modulators / Q000097:blood; D002853:Chromatography, Liquid; D063388:Endocannabinoids; D004983:Ethanolamines; D005989:Glycerides / Q000097:blood; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics; D008875:Middle Aged; D009422:Nervous System Diseases / Q000175:diagnosis; D010169:Palmitic Acids / Q000097:blood*; D053284:Polyunsaturated Alkamides / Q000097:blood*; D020521:Stroke / Q000209:etiology*
chemical_list: D000577:Amides; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D004983:Ethanolamines; D005989:Glycerides; D010169:Palmitic Acids; D053284:Polyunsaturated Alkamides; C005958:palmidrol; C094503:glyceryl 2-arachidonate; C078814:anandamide
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