N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone reduces severity of experimental spinal cord injury

Tiziana Genovese, Emanuela Mazzon, Emanuela Esposito, Carmelo Muià, Rosanna Di Paola, Concetta Crisafulli, Placido Bramanti, Salvatore Cuzzocrea

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)258-265
Number of pages8
JournalShock
Volume27
Issue number3
DOIs
Publication statusPublished - Mar 2007

Keywords

  • Apoptosis
  • Caspases
  • Injury
  • Spinal cord injury
  • z-VAD-fmk

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology

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