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N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone reduces severity of experimental spinal cord injury.
Shock. 2007 Mar; 27(3):258-65.S

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.

Authors+Show Affiliations

Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17304106

Citation

Genovese, Tiziana, et al. "N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone Reduces Severity of Experimental Spinal Cord Injury." Shock (Augusta, Ga.), vol. 27, no. 3, 2007, pp. 258-65.
Genovese T, Mazzon E, Esposito E, et al. N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone reduces severity of experimental spinal cord injury. Shock. 2007;27(3):258-65.
Genovese, T., Mazzon, E., Esposito, E., Muià, C., Di Paola, R., Crisafulli, C., Bramanti, P., & Cuzzocrea, S. (2007). N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone reduces severity of experimental spinal cord injury. Shock (Augusta, Ga.), 27(3), 258-65.
Genovese T, et al. N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone Reduces Severity of Experimental Spinal Cord Injury. Shock. 2007;27(3):258-65. PubMed PMID: 17304106.
* Article titles in AMA citation format should be in sentence-case
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 - 2007/2/17/pubmed PY - 2007/7/21/medline PY - 2007/2/17/entrez SP - 258 EP - 65 JF - Shock (Augusta, Ga.) JO - Shock VL - 27 IS - 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. SN - 1073-2322 UR - https://www.unboundmedicine.com/medline/citation/17304106/N_benzyloxycarbonyl_Val_Ala_Asp_fluoromethylketone_reduces_severity_of_experimental_spinal_cord_injury_ L2 - https://doi.org/10.1097/01.shk.0000239775.41022.54 DB - PRIME DP - Unbound Medicine ER -