title: N-Palmitoylethanolamine Prevents the Run-down of Amplitudes in Cortical Spreading Depression Possibly Implicating Proinflammatory Cytokine Release.
abstract: Cortical spreading depression (CSD), a wave of neuronal depolarization in the cerebral cortex following traumatic brain injury or cerebral ischemia, significantly aggravates brain damage. Here, we tested whether N-palmitoylethanolamine (PEA), a substance that effectively reduces lesion volumes and neurological deficits after ischemic stroke, influences CSD. CSD was elicited chemically in adult rats and occurrence, amplitude, duration and propagation velocity of CSD was determined prior to and for 6 hours after intraperitoneal injection of PEA. The chosen systemic administration of PEA stabilized the amplitude of CSD for at least four hours and prevented the run-down of amplitudes that is typically observed and was also seen in untreated controls. The propagation velocity of the CSD waves was unaltered indicating stable neuronal excitability. The stabilization of CSD amplitudes by PEA indicates that inhibition or prevention of CSD does not underlie PEA's profound neuroprotective effect. Rather, PEA likely inhibits proinflammatory cytokine release thereby preventing the run-down of CSD amplitudes. This contribution of PEA to the maintenance of neuronal excitability in healthy tissue during CSD potentially adds to neuroprotection outside a damaged area, while other mechanisms control PEA-mediated neuroprotection in damaged tissue resulting from traumatic brain injury or cerebral ischemia.
authors.affiliation: Institute of Physiology I/Neurophysiology, Jena University Hospital-Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Richter
authors.affiliation: Vision Research Center, Department of Ophthalmology, University of Missouri - Kansas City, School of Medicine, 2411 Holmes St., Kansas City, MO 64108, USA.|Department of Basic Medical Science, University of Missouri - Kansas City, School of Medicine, 2411 Holmes St., Kansas City, MO 64108, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Koulen
authors.affiliation: Vision Research Center, Department of Ophthalmology, University of Missouri - Kansas City, School of Medicine, 2411 Holmes St., Kansas City, MO 64108, USA.|Departments of Ophthalmology and Molecular Pharmacology and Therapeutics, Loyola University Chicago, Stritch School of Medicine, 2160 South First Ave., Maywood, IL 60153, USA.|Edward Hines Jr. VA Hospital, Research Service, 5000 S Fifth Ave., Hines, IL 60141, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Kaja
mesh_terms: D000577:Amides; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000494:pharmacology; D001921:Brain / Q000502:physiology*; D013181:Cortical Spreading Depression / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D004983:Ethanolamines / Q000008:administration & dosage* / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D010169:Palmitic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats
chemical_list: D000577:Amides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004983:Ethanolamines; D010169:Palmitic Acids; C005958:palmidrol