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Open Access Highly Accessed Research article

MK801 attenuates secondary injury in a mouse experimental compression model of spinal cord trauma

Emanuela Esposito12, Irene Paterniti1, Emanuela Mazzon2, Tiziana Genovese1, Maria Galuppo1, Rosaria Meli3, Placido Bramanti2 and Salvatore Cuzzocrea12*

  • * Corresponding author: Salvatore Cuzzocrea salvator@unime.it

  • † Equal contributors

Author affiliations

1 Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy

2 IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy

3 Department of Experimental Pharmacology, University of Naples Federico II, Italy

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Citation and License

BMC Neuroscience 2011, 12:31  doi:10.1186/1471-2202-12-31

Published: 14 April 2011

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.