Abstract |
The aim of this study was to investigate the effects of N- benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketones ( z-VAD-fmk) on the degree of experimental spinal cord trauma induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration, production of a range of inflammatory mediators, tissue damage, and apoptosis. Treatment of the mice with z-VAD-fmk, a potent broad specific caspase inhibitor, significantly reduced the degree of (1) spinal cord inflammation and tissue injury (histological score), (2) neutrophil infiltration ( myeloperoxidase activity), (3) nitrotyrosine formation, and (4) apoptosis (TUNEL staining and Bax and Bcl-2 expression). In a separate set of experiments, z-VAD-fmk significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with z-VAD-fmk reduces the development of inflammation and tissue injury associated with spinal cord trauma.
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Authors | Tiziana Genovese, Emanuela Mazzon, Emanuela Esposito, Carmelo Muià, Rosanna Di Paola, Concetta Crisafulli, Placido Bramanti, Salvatore Cuzzocrea |
Journal | Shock (Augusta, Ga.)
(Shock)
Vol. 27
Issue 3
Pg. 258-65
(Mar 2007)
ISSN: 1073-2322 [Print] United States |
PMID | 17304106
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amino Acid Chloromethyl Ketones
- Neuroprotective Agents
- Proto-Oncogene Proteins c-bcl-2
- bcl-2-Associated X Protein
- benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
- Peroxidase
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Topics |
- Amino Acid Chloromethyl Ketones
(pharmacology)
- Animals
- Apoptosis
- Blotting, Western
- Humans
- In Situ Nick-End Labeling
- Inflammation
- Male
- Mice
- Neuroprotective Agents
(pharmacology)
- Neutrophils
(metabolism)
- Peroxidase
(metabolism)
- Proto-Oncogene Proteins c-bcl-2
(metabolism)
- Spinal Cord Injuries
(drug therapy)
- bcl-2-Associated X Protein
(metabolism)
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