title: Hydrogen sulfide-releasing cyclooxygenase inhibitor ATB-346 enhances motor function and reduces cortical lesion volume following traumatic brain injury in mice.
abstract: BACKGROUND
  Traumatic brain injury (TBI) induces secondary injury mechanisms, including dynamic interplay between ischemic, inflammatory and cytotoxic processes. We recently reported that administration of ATB-346 (2-(6-methoxynapthalen- 2-yl)-propionic acid 4-thiocarbamoyl-phenyl ester), a hydrogen sulfide-releasing cyclooxygenase inhibitor, showed marked beneficial effects in an animal model of spinal cord injury, significantly enhancing recovery of motor function and reducing the secondary inflammation and tissue injury.
  
  
  METHODS
  Here we evaluated the neuroprotective potential of ATB-346, a hydrogen sulfide-releasing derivative of naproxen, using the controlled cortical impact (CCI) injury model in mice, one of the most common models of TBI. Moreover, the aim of the present study was to carefully investigate molecular pathways and subtypes of glial cells involved in the protective effect of ATB-346 on inflammatory reaction associated with an experimental model of TBI. In these studies, TBI was induced in mice by CCI and mice were orally administered ATB-346, naproxen (both at 30 μmol/kg) or vehicle (dimethylsulfoxide:1% carboxymethylcellulose [5:95] suspension) one and six hours after brain trauma and once daily for 10 days.
  
  
  RESULTS
  Results revealed that ATB-346 attenuated TBI-induced brain edema, suppressed TBI-induced neural cell death and improved neurological function. ATB-346 also significantly reduced the severity of inflammation and restored neurotrophic factors that characterized the secondary events of TBI.
  
  
  CONCLUSIONS
  These data demonstrate that ATB-346 can be efficacious in a TBI animal model by reducing the secondary inflammation and tissue injury. Therefore, ATB-346 could represent an interesting approach for the management of secondary damage following CNS diseases, counteracting behavioral changes and inflammatory process.
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166, Messina, Italy. campolom@unime.it.
authors.forename: Michela
authors.initials: M
authors.lastname: Campolo
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166, Messina, Italy. eesposito@unime.it.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166, Messina, Italy. aahmad@unime.it.
authors.forename: Akbar
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166, Messina, Italy. dipaolar@unime.it.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166, Messina, Italy. irene.paterniti@unime.it.
authors.forename: Irene
authors.initials: I
authors.lastname: Paterniti
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166, Messina, Italy. cordarom@unime.it.
authors.forename: Marika
authors.initials: M
authors.lastname: Cordaro
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166, Messina, Italy. bruschettag@unime.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bruschetta
authors.affiliation: Inflammation Research Network, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4 N1, Canada. wallacej@ucalgary.ca.
authors.forename: John L
authors.initials: JL
authors.lastname: Wallace
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166, Messina, Italy. salvator@unime.it.|Manchester Biomedical Research Centre, Manchester Royal Infirmary, School of Medicine, University of Manchester, 29 Grafton Street Manchester, M13 9WU, Manchester, UK. salvator@unime.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D051379:Mice; D019957:Motor Skills Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009288:Naproxen / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D009929:Organ Size; D011897:Random Allocation
chemical_list: C550692:2-(6-methoxy-napthalen-2-yl)-propionic acid 4-thiocarbamoyl-phenyl ester; D016861:Cyclooxygenase Inhibitors; D009288:Naproxen; D006862:Hydrogen Sulfide