Endogenous levels of the endocannabinoid anandamide, and the activities of the synthesizing and hydrolyzing enzymes, i.e. N-acylphosphatidylethanolamine-hydrolyzing phospholipase D and fatty acid amide hydrolase, respectively, were determined in the cortex and the striatum of rats subjected to transient middle cerebral artery occlusion. Anandamide content was markedly increased (similar to 3-fold over controls; P < 0.01) in the ischemic striatum after 2 h of middle cerebral artery occlusion, but not in the cortex, and this elevation was paralleled by increased activity of N-acylphosphatidylethanolamine-hydrolyzing phospholipase D (similar to 1.7-fold; P < 0.01), and reduced activity (similar to 0.6-fold; P < 0.01) and expression (similar to 0.7-fold; P < 0.05) of fatty acid amide hydrolase. These effects of middle cerebral artery occlusion were further potentiated by 1 h of reperfusion, whereas anandamide binding to type 1 cannabinoid and type 1 vanilloid receptors was not affected significantly by the ischemic insult. Additionally, the cannabinoid type 1 receptor antagonist SR141716, but not the receptor agonist R-(+)-WIN55,212-2, significantly reduced (33%; P < 0.05) cerebral infarct volume detected 22 h after the beginning of reperfusion. A neuroprotective intraperitoneal dose of 17 beta-estradiol (0.20 mg.kg(-1)) that reduced infarct size by 43% also minimized the effect of brain ischemia on the endocannabinoid system, in an estrogen receptor-dependent manner. In conclusion, we show that the endocannabinoid system is implicated in the pathophysiology of transient middle cerebral artery occlusion-induced brain damage, and that neuroprotection afforded by estrogen is coincident with a re-establishment of anandamide levels in the ischemic striatum through a mechanism that needs to be investigated further.

Amantea, D., Spagnuolo, P., Bari, M., Fezza, F., Mazzei, C., Tassorelli, C., et al. (2007). Modulation of the endocannabinoid system by focal brain ischemia in the rat is involved in neuroprotection afforded by 17 beta-estradiol. THE FEBS JOURNAL, 274(17), 4464-4475 [10.1111/j.1742-4658.2007.05975.x].

Modulation of the endocannabinoid system by focal brain ischemia in the rat is involved in neuroprotection afforded by 17 beta-estradiol

FEZZA, FILOMENA;
2007-01-01

Abstract

Endogenous levels of the endocannabinoid anandamide, and the activities of the synthesizing and hydrolyzing enzymes, i.e. N-acylphosphatidylethanolamine-hydrolyzing phospholipase D and fatty acid amide hydrolase, respectively, were determined in the cortex and the striatum of rats subjected to transient middle cerebral artery occlusion. Anandamide content was markedly increased (similar to 3-fold over controls; P < 0.01) in the ischemic striatum after 2 h of middle cerebral artery occlusion, but not in the cortex, and this elevation was paralleled by increased activity of N-acylphosphatidylethanolamine-hydrolyzing phospholipase D (similar to 1.7-fold; P < 0.01), and reduced activity (similar to 0.6-fold; P < 0.01) and expression (similar to 0.7-fold; P < 0.05) of fatty acid amide hydrolase. These effects of middle cerebral artery occlusion were further potentiated by 1 h of reperfusion, whereas anandamide binding to type 1 cannabinoid and type 1 vanilloid receptors was not affected significantly by the ischemic insult. Additionally, the cannabinoid type 1 receptor antagonist SR141716, but not the receptor agonist R-(+)-WIN55,212-2, significantly reduced (33%; P < 0.05) cerebral infarct volume detected 22 h after the beginning of reperfusion. A neuroprotective intraperitoneal dose of 17 beta-estradiol (0.20 mg.kg(-1)) that reduced infarct size by 43% also minimized the effect of brain ischemia on the endocannabinoid system, in an estrogen receptor-dependent manner. In conclusion, we show that the endocannabinoid system is implicated in the pathophysiology of transient middle cerebral artery occlusion-induced brain damage, and that neuroprotection afforded by estrogen is coincident with a re-establishment of anandamide levels in the ischemic striatum through a mechanism that needs to be investigated further.
2007
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/10 - BIOCHIMICA
English
Endocannabinoids; Estrogen; Middle cerebral artery occlusion; Stroke
Amantea, D., Spagnuolo, P., Bari, M., Fezza, F., Mazzei, C., Tassorelli, C., et al. (2007). Modulation of the endocannabinoid system by focal brain ischemia in the rat is involved in neuroprotection afforded by 17 beta-estradiol. THE FEBS JOURNAL, 274(17), 4464-4475 [10.1111/j.1742-4658.2007.05975.x].
Amantea, D; Spagnuolo, P; Bari, M; Fezza, F; Mazzei, C; Tassorelli, C; Morrone, La; Corasaniti, Mt; Maccarrone, M; Bagetta, G
Articolo su rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/39163
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