INTRACELLULAR MECHANISMS OF N-ACYLETHANOLAMINE-MEDIATED NEUROPROTECTION IN A RAT MODEL OF STROKE

被引:46
作者
Garg, P. [3 ]
Duncan, R. S. [1 ,2 ]
Kaja, S. [1 ,2 ]
Koulen, P. [1 ,2 ]
机构
[1] Univ Missouri, Dept Basic Med Sci, Kansas City, MO 64108 USA
[2] Univ Missouri, Dept Ophthalmol, Kansas City, MO 64108 USA
[3] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA
关键词
neurodegeneration; neuroprotection; receptors; ischemia; ACYL-ETHANOLAMINE PHOSPHOLIPIDS; FATTY-ACID AMIDES; KAPPA-B; CANNABINOID RECEPTORS; CEREBRAL-ISCHEMIA; MOLECULAR-MECHANISMS; VANILLOID RECEPTORS; NITRIC-OXIDE; P-31; NMR; BRAIN;
D O I
10.1016/j.neuroscience.2009.11.069
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
N-acyl ethanolamines (NAEs) are endogenous lipids that are synthesized in response to tissue injury, including ischemia and stroke, suggesting they may exhibit neuroprotective properties. We hypothesized that NAE 16:0 (palmitoylethanolamine) is neuroprotective against ischemia-reperfusion injury in rats, a widely employed model of stroke, and that neuroprotection is mediated through an intracellular mechanism independent of known NAE receptors. Administration of NAE 16:0 from 30 min before to 2 h after stroke significantly reduced cortical and subcortical infarct volume, and correlated with an improvement of the neurological phenotype, as assessed by the neurological deficit score. We here show that NAE 16:0-mediated neuroprotection was independent of cannabinoid (CB1) and vanilloid (VR1) receptor activation, known NAE receptors on the plasma membrane, as determined by inclusion of specific inhibitors. The inclusion of an NAE uptake inhibitor (AM404), however, completely reversed NAE 16:0-mediated neuroprotection, suggesting that NAE 16:Os effects are through an intracellular mechanism. NAE 16:0 produced a significant reduction in the number of cells undergoing apoptosis and reversed ischemia-induced upregulation of several proteins, including inducible nitric oxide synthase and transcription factor NF kappa B. Our findings suggest that NAE 16:0-mediated neuroprotection is due to the reduction of neuronal apoptosis and inflammation in the brain. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:252 / 262
页数:11
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