title: Neuroprotective Effects of Co-UltraPEALut on Secondary Inflammatory Process and Autophagy Involved in Traumatic Brain Injury.
abstract: Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to neuronal damage and behavioral impairment. In the present study, we performed a widely used model of TBI to determine the neuroprotective propriety of palmitoylethanolamide (PEA) and the antioxidant effect of a flavonoid luteolin (Lut), given as a co-ultramicronized compound Co-ultraPEALut. We demonstrated that the treatment with Co-ultraPEALut resulted in a significant improvement of motor and cognitive recovery after controlled cortical impact, as well as markedly reducing lesion volumes. Moreover, our results revealed the ability of Co-ultraPEALut to reduce brain trauma through modulation of nuclear factor-κB activation. In addition, treatment with Co-ultraPEALut significantly enhanced the post-TBI expression of the neuroprotective neurotrophins glial cell line-derived neurotrophic factor compared with vehicle. Co-ultraPEALut at the dose of 1 mg/kg also modulated apoptosis, the release of cytokine and reactive oxygen species, the activation of chymase, tryptase, and nitrotyrosine, and inhibited autophagy. Thus, our data demonstrated that Co-ultraPEALut at a lower dose compared with PEA alone can exert neuroprotective effects and the combination of both could improve their ability to counteract the neurodegeneration and neuroinflammation induced by TBI.
authors.affiliation: 1 Department of Biological and Environmental Sciences, University of Messina , Messina, Italy .
authors.forename: Marika
authors.initials: M
authors.lastname: Cordaro
authors.affiliation: 1 Department of Biological and Environmental Sciences, University of Messina , Messina, Italy .
authors.forename: Daniela
authors.initials: D
authors.lastname: Impellizzeri
authors.affiliation: 1 Department of Biological and Environmental Sciences, University of Messina , Messina, Italy .
authors.forename: Irene
authors.initials: I
authors.lastname: Paterniti
authors.affiliation: 1 Department of Biological and Environmental Sciences, University of Messina , Messina, Italy .
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bruschetta
authors.affiliation: 1 Department of Biological and Environmental Sciences, University of Messina , Messina, Italy .
authors.forename: Rosalba
authors.initials: R
authors.lastname: Siracusa
authors.affiliation: 2 Department of Experimental Pharmacology, University of Naples Federico II , Naples, Italy .
authors.forename: Daniela
authors.initials: D
authors.lastname: De Stefano
authors.affiliation: 1 Department of Biological and Environmental Sciences, University of Messina , Messina, Italy .|3 Manchester Biomedical Research Centre, Manchester Royal Infirmary, School of Medicine, University of Manchester , Manchester, United Kingdom .
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.affiliation: 1 Department of Biological and Environmental Sciences, University of Messina , Messina, Italy .
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D047311:Luteolin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D004338:Drug Combinations; D004983:Ethanolamines; D018696:Neuroprotective Agents; C000610984:co-ultraPEALut; D047311:Luteolin
keywords: autophagy; inflammation; luteolin; neuroprotection; palmitoylethanolamide