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

Emanuela Esposito,Emanuela Mazzon,Tiziana Genovese,Placido Bramanti,Rosaria Meli,Salvatore Cuzzocrea,Maria Galuppo,Irene Paterniti

doi:10.1186/1471-2202-12-31

Abstract

BackgroundGlutamergic 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.ResultsSpinal 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.ConclusionsBlockade of NMDA by MK801 lends support to the potential importance of NMDA antagonists as therapeutic agents in the treatment of acute spinal cord injury.

Highlights

Glutamergic excitotoxicity has been shown to play a deleterious role in the pathophysiology of spinal cord injury (SCI)
3.1 MK801 treatment reduces the severity of spinal cord trauma The severity of the trauma at the level of the perilesional area, assessed by the presence of edema as well as alteration of the white matter and infiltration of leukocytes, was evaluated 24 h after injury by hematoxylin/ eosin (H&E) staining
Protection against injury was observed in SCI-operated mice that have been treated with MK801at the dose of 2 mg/kg administered i.p. 30 min and 6 hours after trauma (Figure 1c see histological score g)

Summary

Introduction

Glutamergic excitotoxicity has been shown to play a deleterious role in the pathophysiology of spinal cord injury (SCI). Glutamate is involved in fast excitatory transmission and plays important roles in neuronal function such as plasticity and cognitive processes, as well as in toxic events [3]. It is stored in synaptic vesicles and released by calcium (Ca2+)-dependent exocytosis in the white matter of the brain [4]. The overstimulation of glutamate receptors is toxic either to neuron and glial cells and participates in processes culminating in programmed cell death [12,13]

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