title: Reduction of ischemic brain injury by administration of palmitoylethanolamide after transient middle cerebral artery occlusion in rats.
abstract: Stroke is the third leading cause of death and the leading cause of long-term disability in adults. Current therapeutic strategies for stroke, including thrombolytic drugs, such as tissue plasminogen activator offer great promise for the treatment, but complimentary neuroprotective treatments are likely to provide a better outcome. To counteract the ischemic brain injury in mice, a new therapeutic approach has been employed by using palmitoylethanolamide (PEA). PEA is one of the members of N-acyl-ethanolamine family maintain not only redox balance but also inhibit the mechanisms of secondary injury on ischemic brain injury. Treatment of the middle cerebral artery occlusion (MCAo)-induced animals with PEA reduced edema and brain infractions as evidenced by decreased 2,3,5-triphenyltetrazolium chloride (TTC) staining across brain sections. PEA-mediated improvements in tissues histology shown by reduction of lesion size and improvement in apoptosis level (assayed by Bax and Bcl-2) further support the efficacy of PEA therapy. We demonstrated that PEA treatment blocked infiltration of astrocytes and restored MCAo-mediated reduced expression of PAR, nitrotyrosine, iNOS, chymase, tryptase, growth factors (BDNF and GDNF) and GFAP. PEA also inhibited the MCAo-mediated increased expression of pJNK, NF-κB, and degradation of IκB-α. PEA-treated injured animals improved neurobehavioral functions as evaluated by motor deficits. Based on these findings we propose that PEA would be useful in lowering the risk of damage or improving function in ischemia-reperfusion brain injury-related disorders.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, Messina, Italy.
authors.forename: Akbar
authors.initials: A
authors.lastname: Ahmad
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.forename: Daniela
authors.initials: D
authors.lastname: Impellizzeri
authors.forename: Rosalia
authors.initials: R
authors.lastname: Crupi
authors.forename: Enrico
authors.initials: E
authors.lastname: Velardi
authors.forename: Angela
authors.initials: A
authors.lastname: Marino
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000577:Amides; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology*; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000008:administration & dosage*; D004983:Ethanolamines / Q000008:administration & dosage*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010169:Palmitic Acids / Q000008:administration & dosage*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy; D013778:Tetrazolium Salts; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D000577:Amides; D063388:Endocannabinoids; D004983:Ethanolamines; D005904:Glial Fibrillary Acidic Protein; D048031:JNK Mitogen-Activated Protein Kinases; D018696:Neuroprotective Agents; D052247:Nitric Oxide Synthase Type II; D010169:Palmitic Acids; D017346:Protein Serine-Threonine Kinases; D013778:Tetrazolium Salts; D014409:Tumor Necrosis Factor-alpha; D000097782:NF-kappaB-Inducing Kinase; C005958:palmidrol; C009591:triphenyltetrazolium