Naccarato, Marcello (2008) Endocannabinoidi e stroke: uno studio nell'uomo. [Ph.D. thesis]
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Background: Endocannabinoids have shown neuroprotective properties in murine and neuronal coltural models of stroke, acting on NMDA-mediated excitotoxicity and probably modulating the subsequent neuroinflammatory response.
Methods: 10 patients with a first ischemic stroke in the MCA territory with at least hand movement impairment and 8 age-matched control subjects were included. Groups were matched for body mass index (BMI) and plasmatic fasting glucose, cholesterol and triglyceride levels. All control subjects underwent a blood sample collection for anandamide (AEA), 2-arachidonoylglycerol (2-AG) and palmitoylethanolamide (PEA) measurement; patients admitted within 6 hours since stroke onset underwent the same procedure on admittance (T0), after 12 (T1) and after 24 (T2) hours since symptom onset. Patient’s neurological impairment was assessed using NIHSS and Fugl-Meyer Scale arm subitem (FMS); stroke volume was determined on 48-hours follow-up brain CT scans. Blood samples were analyzed by liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry. Statistical analysis was performed with SPSS 12.0, using Mann-Whitney U test and Spearman correlation analysis.
Results: 1)The T0 levels of AEA, but not 2-AG and PEA, were significantly higher in stroke patients compared to control subjects. 2) There was a correlation between BMI, cholesterol, glucose and triglyceride plasmatic levels and 2-AG, but not AEA, levels. 3) Stroke patients showed a significant inverse correlation between T0 AEA levels and FMS score: the higher the AEA levels, the worse the neurological arm impairment. PEA T0 levels showed a significant direct correlation with NIHSS score. Finally, a positive correlation trend was found between T0 AEA levels and stroke volume at 48-hours follow-up brain CT scans.
Conclusions: This is the first demonstration of elevated peripheral AEA levels in stroke patients; moreover, like in previous murine studies, there seems to be a significant relationship between AEA levels and neurological impairment at 6 hours since stroke onset.
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