Research Article
Aruna Kilaru, Pamela Tamura
Abstract
In mammals, the endocannabinoid signaling pathway provides protective cellular responses to ischemia. Previous work demonstrated increases in long-chain N-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 of N-palmitoylethanolamine (NAE 16:0) prior to ischemia on NAE metabolite and phospholipid profiles was measured. While ischemia, in general, resulted in elevated levels of N-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.