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Possible Anandamide and Palmitoylethanolamide involvement in human stroke.

Naccarato M, Pizzuti D, Petrosino S, Simonetto M, Ferigo L, Grandi FC, Pizzolato G, Di Marzo V - Lipids Health Dis (2010)

Bottom Line: Blood samples were analyzed by liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry. 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.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.

View Article: PubMed Central - HTML - PubMed

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

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.

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Related in: MedlinePlus

Follow-up brain CT scans of two stroke patients. Two examples of CT scans of two stroke patients at 48 hours since admission. The red outline circumscribes the ischemic area. The patient in panel A had a total occlusion of right middle cerebral artery, presenting with left hemiparesis and hemianopia (Female; Age = 80 yrs.; T0 AEA = 7.31 pmol/lipid mg; T0 NIHSS = 17; T0 aFMS score = 12). The patient in panel B was admitted for a left hemiparesis due to a partial occlusion in right middle cerebral artery territory (Female, Age = 82 yrs.; T0 AEA = 3.93 pmol/lipid mg; T0 NIHSS = 10; T0 aFMS score = 18).
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Figure 1: Follow-up brain CT scans of two stroke patients. Two examples of CT scans of two stroke patients at 48 hours since admission. The red outline circumscribes the ischemic area. The patient in panel A had a total occlusion of right middle cerebral artery, presenting with left hemiparesis and hemianopia (Female; Age = 80 yrs.; T0 AEA = 7.31 pmol/lipid mg; T0 NIHSS = 17; T0 aFMS score = 12). The patient in panel B was admitted for a left hemiparesis due to a partial occlusion in right middle cerebral artery territory (Female, Age = 82 yrs.; T0 AEA = 3.93 pmol/lipid mg; T0 NIHSS = 10; T0 aFMS score = 18).

Mentions: Twenty-eight contiguous 5 mm-thick axial slices, covering the whole brain, were obtained for each patient with a multislice TOSHIBA AQUILION scanner, with 120 kV, 250 mA and 2 s acquisition time (Toshiba Medical Systems). Thereafter, using Analyze 4.5 (Biomedical Imaging Resource, Mayo University) and a semi-automated routine, two blinded examiners (FCG and GP) calculated the total lesion volume in mL, as the sum of the stroke area in each slice multiplied by slice thickness (Fig. 1).


Possible Anandamide and Palmitoylethanolamide involvement in human stroke.

Naccarato M, Pizzuti D, Petrosino S, Simonetto M, Ferigo L, Grandi FC, Pizzolato G, Di Marzo V - Lipids Health Dis (2010)

Follow-up brain CT scans of two stroke patients. Two examples of CT scans of two stroke patients at 48 hours since admission. The red outline circumscribes the ischemic area. The patient in panel A had a total occlusion of right middle cerebral artery, presenting with left hemiparesis and hemianopia (Female; Age = 80 yrs.; T0 AEA = 7.31 pmol/lipid mg; T0 NIHSS = 17; T0 aFMS score = 12). The patient in panel B was admitted for a left hemiparesis due to a partial occlusion in right middle cerebral artery territory (Female, Age = 82 yrs.; T0 AEA = 3.93 pmol/lipid mg; T0 NIHSS = 10; T0 aFMS score = 18).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2877050&req=5

Figure 1: Follow-up brain CT scans of two stroke patients. Two examples of CT scans of two stroke patients at 48 hours since admission. The red outline circumscribes the ischemic area. The patient in panel A had a total occlusion of right middle cerebral artery, presenting with left hemiparesis and hemianopia (Female; Age = 80 yrs.; T0 AEA = 7.31 pmol/lipid mg; T0 NIHSS = 17; T0 aFMS score = 12). The patient in panel B was admitted for a left hemiparesis due to a partial occlusion in right middle cerebral artery territory (Female, Age = 82 yrs.; T0 AEA = 3.93 pmol/lipid mg; T0 NIHSS = 10; T0 aFMS score = 18).
Mentions: Twenty-eight contiguous 5 mm-thick axial slices, covering the whole brain, were obtained for each patient with a multislice TOSHIBA AQUILION scanner, with 120 kV, 250 mA and 2 s acquisition time (Toshiba Medical Systems). Thereafter, using Analyze 4.5 (Biomedical Imaging Resource, Mayo University) and a semi-automated routine, two blinded examiners (FCG and GP) calculated the total lesion volume in mL, as the sum of the stroke area in each slice multiplied by slice thickness (Fig. 1).

Bottom Line: Blood samples were analyzed by liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry. 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.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.

View Article: PubMed Central - HTML - PubMed

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

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.

Show MeSH
Related in: MedlinePlus