Modulation of inflammatory response after spinal cord trauma with deferoxamine, an iron chelator

Abstract

The standard iron-chelator deferoxamine is known to reduce neurological deficits. The aim of the present study was to evaluate the contribution of deferoxamine in the secondary damage in experimental spinal cord injury (SCI) in mice, induced by the application of vascular clips to the dura via a four-level T5–T8 laminectomy. SCI resulted in production of inflammatory mediators, tissue damage and apoptosis. Deferoxamine treatment 30 min before and 1 and 6 h after the SCI significantly reduced: (1) GFAP immunoreactivity, (2) neutrophil infiltration, (3) NF-κB activation, (4) iNOS expression, (5) nitrotyrosine and MDA formation, (6) DNA damage (methyl green pyronin staining and PAR formation and (7) apoptosis (TUNEL staining, FasL, Bax and Bcl-2 expression, S-100 expression). Moreover, deferoxamine significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, the results clearly demonstrate that deferoxamine treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma.

Keywords::

• SCI
• inflammatory mediators
• tissue damage
• apoptosis

Acknowledgements

We thank Carmelo La Spada for excellent technical assistance during this study, Caterina Cutrona for secretarial assistance and Valentina Malvagni for editorial assistance with the paper.

Declaration of interest: This study was supported by a grant from IRCCS Centro Neurolesi ‘Bonino-Pulejo’, Messina, Italy (SC). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This paper was first published online on Early online on 07 April 2010.