Intracellular mechanisms of N-acylethanolamine-mediated neuroprotection in a rat model of stroke.

Abstract

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 16:0s 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 NFkappaB. Our findings suggest that NAE 16:0-mediated neuroprotection is due to the reduction of neuronal apoptosis and inflammation in the brain.

• Authors: P Garg, R S Duncan, S Kaja, P Koulen
• Journal: Neuroscience (Neuroscience) Vol. 166 Issue 1 Pg. 252-62 (Mar 10 2010) ISSN: 1873-7544 [Electronic] United States
• PMID: 19963043 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Ethanolamines
• N-acylethanolamines
• NF-kappa B
• Nerve Tissue Proteins
• Neuroprotective Agents
• Nitric Oxide
• Nitric Oxide Synthase Type II

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Brain Ischemia (drug therapy, metabolism, physiopathology)
• Cytoprotection (drug effects, physiology)
• Disease Models, Animal
• Encephalitis (drug therapy, metabolism, physiopathology)
• Ethanolamines (pharmacology)
• Immunohistochemistry
• Infarction, Middle Cerebral Artery (drug therapy, metabolism, physiopathology)
• Male
• NF-kappa B (drug effects, metabolism)
• Nerve Degeneration (drug therapy, physiopathology, prevention & control)
• Nerve Tissue Proteins (drug effects, metabolism)
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley
• Recovery of Function (drug effects, physiology)
• Stroke (drug therapy, metabolism, physiopathology)
• Treatment Outcome