TY - JOUR
T1 - N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone reduces severity of experimental spinal cord injury
AU - Genovese, Tiziana
AU - Mazzon, Emanuela
AU - Esposito, Emanuela
AU - Muià, Carmelo
AU - Di Paola, Rosanna
AU - Crisafulli, Concetta
AU - Bramanti, Placido
AU - Cuzzocrea, Salvatore
PY - 2007/3
Y1 - 2007/3
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Caspases
KW - Injury
KW - Spinal cord injury
KW - z-VAD-fmk
UR - http://www.scopus.com/inward/record.url?scp=33847049333&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33847049333&partnerID=8YFLogxK
U2 - 10.1097/01.shk.0000239775.41022.54
DO - 10.1097/01.shk.0000239775.41022.54
M3 - Article
C2 - 17304106
AN - SCOPUS:33847049333
VL - 27
SP - 258
EP - 265
JO - Shock
JF - Shock
SN - 1073-2322
IS - 3
ER -