Modulation of inflammatory response after spinal cord trauma with deferoxamine, an iron chelator.
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-kappaB 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.
Paterniti
Irene
I
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, Gazzi, Messina, Italy.
Mazzon
Emanuela
E
Emanuela
Esposito
E
Paola
Rosanna Di
RD
Galuppo
Maria
M
Bramanti
Placido
P
Cuzzocrea
Salvatore
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D003676:Deferoxamine / Q000627:therapeutic use*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
D018836:Inflammation Mediators; D007502:Iron Chelating Agents; D003676:Deferoxamine