title: MK801 attenuates secondary injury in a mouse experimental compression model of spinal cord trauma.
abstract: BACKGROUND
  Glutamergic excitotoxicity has been shown to play a deleterious role in the pathophysiology of spinal cord injury (SCI). The aim of this study was to investigate the neuroprotective effect of dizocilpine maleate, MK801 (2 mg/Kg, 30 min and 6 hours after injury) in a mice model of SCI. The spinal cord trauma was induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy.
  
  
  RESULTS
  Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration and apoptosis. In this study we clearly demonstrated that administration of MK801 attenuated all inflammatory parameters. In fact 24 hours after injury, the degree of spinal cord inflammation and tissue injury (evaluated as histological score), infiltration of neutrophils, NF-κB activation, iNOS, cytokines levels (TNF-α and IL-1β), neurotrophin expression were markedly reduced by MK801 treatment. Moreover, in a separate set of experiments, we have demonstrated that MK801 treatment significantly improved the recovery of locomotory function.
  
  
  CONCLUSIONS
  Blockade of NMDA by MK801 lends support to the potential importance of NMDA antagonists as therapeutic agents in the treatment of acute spinal cord injury.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.forename: Irene
authors.initials: I
authors.lastname: Paterniti
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.forename: Maria
authors.initials: M
authors.lastname: Galuppo
authors.forename: Rosaria
authors.initials: R
authors.lastname: Meli
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology*; D013117:Spinal Cord Compression / Q000503:physiopathology* / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D009414:Nerve Growth Factors; D017470:Receptors, Glutamate; D016291:Dizocilpine Maleate