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. 2010 May 14:9:47.
doi: 10.1186/1476-511X-9-47.

Possible Anandamide and Palmitoylethanolamide involvement in human stroke

Marcello Naccarato  1 , Daniela Pizzuti, Stefania Petrosino, Marco Simonetto, Laura Ferigo, Fabio Chiodo Grandi, Gilberto Pizzolato, Vincenzo Di Marzo
Affiliations

Possible Anandamide and Palmitoylethanolamide involvement in human stroke

Marcello Naccarato et al. Lipids Health Dis. .

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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Figures

Figure 1
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).
Figure 2
Figure 2
Box-plot of plasma AEA levels in control and stroke patient groups (at T0). * At T0, mean plasma AEA levels were significantly higher in the stroke patients group (p < 0.05, Mann-Whitney U test).
Figure 3
Figure 3
Scatterplot of plasma AEA levels versus aFMS score in stroke patients at T0. Significant inverse correlation between AEA levels and aFMS score (Spearman rho = -0.819, p = 0.004).
Figure 4
Figure 4
Scatterplot of plasma PEA levels versus NIHSS score in stroke patients at T0. Significant direct correlation between PEA levels and NIHSS score (Spearman rho = 0.823, p = 0.003).
See this image and copyright information in PMC

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