Endocannabinoids mediate neuroprotection after transient focal cerebral ischemia

• Published in: Brain research Vol. 1240; pp. 213 - 220
• Main Authors: Schomacher, Markus, Müller, Harald D, Sommer, Clemens, Schwab, Stefan, Schäbitz, Wolf-Rüdiger
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 13.11.2008; Elsevier
• Subjects: Anandamide; Animals; Biological and medical sciences; Brain - drug effects; Brain - pathology; Cannabinoid receptor; Cannabinoid Receptor Modulators - pharmacology; Endocannabinoid; Endocannabinoids; Ischemic Attack, Transient - drug therapy; Ischemic Attack, Transient - pathology; Male; Medical sciences; Neurology; Neuroprotection; Neuroprotective Agents - pharmacology; Palmitoylethanolamide; Rats; Rats, Wistar; Recovery of Function - drug effects; Stroke; Vascular diseases and vascular malformations of the nervous system; Neuroprotection; Stroke; Endocannabinoid; Palmitoylethanolamide; Cannabinoid receptor; Anandamide; Nervous system diseases; Rat; Rodentia; Central nervous system; Cardiovascular disease; Cannabinoid; Cerebral disorder; Encephalon; Vascular disease; Vertebrata; Mammalia; Animal; Central nervous system disease; Brain ischemia; Cerebrovascular disease
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2008.09.019

Abstract The endocannabinoids anandamide (AEA) and palmitoylethanolamide (PEA) act as endogenous protective factors of the brain, using different pathways of neuroprotection against neuronal damage. Although several in vivo and in vitro studies confirmed the neuroprotective efficacy of endocannabinoids, no experimental settings compare and explore the neuroprotective potential of AEA and PEA in an acute stroke model. In this study, we investigated the neuroprotective potential by infarct measurement after high (30 mg/kg body weight) and low dosage administration (10 mg/kg body weight) of the endocannabinoid PEA in 49 male Wistar rats. In additions we studied infarct volumes of 22 male Wistar rats receiving the endocannabinoid AEA with a dosage of 10 mg/kg body weight or placebo. The neurological outcome was assessed 24 h after ischemia. Endocannabinoids were given intraperitoneally 30 min after initiation of transient middle cerebral artery occlusion (tMCAO). Infarct volume was calculated on the basis of 2.3.5-triphenyltetrazolium chloride staining. In the PEA high-dose group a significant total infarct reduction of 35% compared to the control group could be observed. AEA-treated rats presented a total infarct reducing effect of 26% compared to controls. Neurological scores, evaluated 24 h after tMCAO and physiological parameters, obtained 45 and 90 min after onset of ischemia showed no significant differences among the groups. As shown here, the endocannabinoids AEA and PEA achieved a significant neuroprotective effect by reducing size of infarcted tissue after tMCAO. Both endocannabinoids may have the potential to treat acute stroke and exert neuroprotection through a variety of mechanisms.