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https://hdl.handle.net/2440/5680
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Type: | Journal article |
Title: | The "dark side" of endocannabinoids: A neurotoxic role for anandamide |
Author: | Cernak, I. Vink, R. Natale, J. Stoica, B. Lea, P. Movesesyan, V. Ahmed, F. Knoblach, S. Fricke, S. Faden, A. |
Citation: | Journal of Cerebral Blood Flow and Metabolism, 2004; 24(5):564-578 |
Publisher: | Lippincott Williams & Wilkins |
Issue Date: | 2004 |
ISSN: | 0271-678X 1559-7016 |
Statement of Responsibility: | Ibolja Cernak, Robert Vink, JoAnne Natale, Bogdan Stoica, Paul M Lea IV, Vilen Movsesyan, Farid Ahmed, Susan M Knoblach, Stanley T Fricke and Alan I Faden |
Abstract: | Endocannabinoids, including 2-arachidonoylglycerol and anandamide (N-arachidonoylethanolamine; AEA), have neuroprotective effects in the brain through actions at CB1 receptors. However, AEA also binds to vanilloid (VR1) receptors and induces cell death in several cell lines. Here we show that anandamide causes neuronal cell death in vitro and exacerbates cell loss caused by stretch-induced axonal injury or trophic withdrawal in rat primary neuronal cultures. Administered intracerebroventricularly, AEA causes sustained cerebral edema, as reflected by diffusion-weighted magnetic resonance imaging, regional cell loss, and impairment in long-term cognitive function. These effects are mediated, in part, through VR1 as well as through calpain-dependent mechanisms, but not through CB1 receptors or caspases. Central administration of AEA also significantly upregulates genes involved in pro-inflammatory/microglial-related responses. Thus, anandamide produces neurotoxic effects both in vitro and in vivo through multiple mechanisms independent of the CB1 receptor. |
Keywords: | endocannabinoids anandamide cell death microarray magnetic resonance imaging cognitive deficit |
Rights: | © 2004 International Society for Cerebral Blood Flow & Metabolism |
DOI: | 10.1097/00004647-200405000-00011 |
Published version: | http://www.nature.com/jcbfm/journal/v24/n5/abs/9591559a.html |
Appears in Collections: | Aurora harvest Pathology publications |
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