Endocannabinoid response in acute ischemic stroke: elevated 2-arachidonoylglycerol

Abstract

Background and purpose: Endocannabinoids are hypothesized to have anti-inflammatory and neuroprotective properties and hold therapeutic potential in the acute phase response mechanisms during acute cerebral ischemia and closed head injury. We set to describe the plasma levels of endocannabinoids and related ethanolamides during acute and subacute phases of cerebral ischemia. Methods: We conducted a prospective observational study of plasma endocannabinoid levels in patients with acute ischemic stroke or transient ischemic attack. Two blood samples were collected: T1 (<12 hours from symptom onset) and T2 (>24 hours from symptom onset). N-arachidonoylethanolamine (AEA), 2-arachidonoylglycerol (2-AG), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) were quantified by liquid chromatography mass spectrometry. Results: Twenty-three patients met inclusion criteria. Median (interquartile range): Age - 76 years (60-81); body mass index - 25.6 (23.6-30.4); National Institutes of Health Stroke Scale score- 5(3-13); infarct volume - 1.4 cm3 (0.5-8.6). Higher 2-AG levels at T1 were correlated with smaller infarct volumes (Spearman rho=-0.48, p=0.0206). Levels of 2-AG were elevated at T2 compared to T1 in 48% of patients (median difference - 310.3nM, 95% CI 194.1-497.3; p=0.001); AEA, PEA and OEA did not differ between T1 and T2, p>0.05. Patients with elevated 2-AG at T2 had larger infarct volumes, p=0.0178, lower frequency of embolectomy performed, p=0.0373, but no difference in neurological disability 90 days after the ischemic event compared to patients without 2-AG elevation. Conclusion: 2-AG increases significantly in early phases of ischemic stroke. The final mechanistic role of 2-AG in acute ischemic stroke is to be determined in further studies.