title: Changes in N-acylethanolamine Pathway Related Metabolites in a Rat Model of Cerebral Ischemia/Reperfusion.
abstract: In mammals, the endocannabinoid signaling pathway provides protective cellular responses to ischemia. Previous work demonstrated increases in long-chainN-acylethanolamines (NAE) in ischemia and suggested a protective role for NAE. Here, a targeted lipidomics approach was used to study comprehensive changes in the molecular composition and quantity of NAE metabolites in a rat model of controlled brain ischemia. Changes of NAE, its precursors,N-acylphosphatidylethanolamines (NAPE), major and minor phospholipids, and free fatty acids (FFA) were quantified in response to ischemia. The effect of intraperitoneal injection ofN-palmitoylethanolamine (NAE 16:0) prior to ischemia on NAE metabolite and phospholipid profiles was measured. While ischemia, in general, resulted in elevated levels ofN-acyl 16:0 and18:0 NAE, NAPE, and FFA species, pretreatment with NAE 16:0 reduced infarct volume, neurological behavioral deficits in rats, and FFA content in ischemic tissues. Pretreatment with NAE 16:0 did not affect the profiles of other NAE metabolites. These studies demonstrate the utility of a targeted lipidomics approach to measure complex and concomitant metabolic changes in response to ischemia. They suggest that the neuroprotective effects of exogenous NAE 16:0 and the reduction in inflammatory damage may be mediated by factors other than gross changes in brain NAE levels, such as modulation of transcriptional responses.
authors.affiliation: University of North Texas, Center for Plant Lipid Research, Department of Biological Sciences, Denton, TX 76203.
authors.forename: Aruna
authors.initials: A
authors.lastname: Kilaru
authors.affiliation: Kansas State University, Kansas Lipidomics Research Center, Division of Biology, Manhattan, KS 66506.
authors.forename: Pamela
authors.initials: P
authors.lastname: Tamura
authors.affiliation: University of Missouri - Kansas City, School of Medicine, Vision Research Center, Kansas City, MO 64108 ; University of Missouri - Kansas City, School of Medicine, Departments of Basic Medical Science and Ophthalmology, Kansas City, MO 64108.
authors.forename: Puja
authors.initials: P
authors.lastname: Garg
authors.affiliation: Kansas State University, Kansas Lipidomics Research Center, Division of Biology, Manhattan, KS 66506.
authors.forename: Giorgis
authors.initials: G
authors.lastname: Isaac
authors.affiliation: University of North Texas, Center for Plant Lipid Research, Department of Biological Sciences, Denton, TX 76203.
authors.forename: David
authors.initials: D
authors.lastname: Baxter
authors.affiliation: University of Missouri - Kansas City, School of Medicine, Vision Research Center, Kansas City, MO 64108 ; University of Missouri - Kansas City, School of Medicine, Departments of Basic Medical Science and Ophthalmology, Kansas City, MO 64108.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Duncan
authors.affiliation: Kansas State University, Kansas Lipidomics Research Center, Division of Biology, Manhattan, KS 66506.
authors.forename: Ruth
authors.initials: R
authors.lastname: Welti
authors.affiliation: University of North Texas, Center for Plant Lipid Research, Department of Biological Sciences, Denton, TX 76203 ; University of Missouri - Kansas City, School of Medicine, Vision Research Center, Kansas City, MO 64108 ; University of Missouri - Kansas City, School of Medicine, Departments of Basic Medical Science and Ophthalmology, Kansas City, MO 64108.
authors.forename: Peter
authors.initials: P
authors.lastname: Koulen
authors.affiliation: University of North Texas, Center for Plant Lipid Research, Department of Biological Sciences, Denton, TX 76203.
authors.forename: Kent D
authors.initials: KD
authors.lastname: Chapman
authors.affiliation: University of North Texas, Center for Plant Lipid Research, Department of Biological Sciences, Denton, TX 76203.
authors.forename: Barney J
authors.initials: BJ
authors.lastname: Venables
keywords: N-acylphosphatidylethanolamine; N-palmitoylethanolamine; free fatty acid; lipid signaling; mass spectrometry; phospholipids