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Immunomodulatory effects of etanercept in an experimental model of spinal cord injury.
J Pharmacol Exp Ther. 2006 Mar; 316(3):1006-16.JP

Abstract

Etanercept is a tumor necrosis factor antagonist with anti-inflammatory effects. The aim of our study was to evaluate for the first time the therapeutic efficacy of in vivo inhibition of tumor necrosis factor-alpha (TNF-alpha) in experimental model of spinal cord trauma, which was 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, and cytokine production that it is followed by recruitment of other inflammatory cells, such as production of a range of inflammation mediators, tissue damage, apoptosis, and disease. Treatment of the mice with etanercept significantly reduced the degree of 1) spinal cord inflammation and tissue injury (histological score); 2) neutrophil infiltration (myeloperoxidase evaluation); 3) inducible nitric-oxide synthase, nitrotyrosine, cyclooxygenase-2, and cytokines expression (TNF-alpha and interleukin-1beta); and 4) apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and Bax and Bcl-2 expression). In a separate set of experiment, we have also clearly demonstrated that TNF-alpha inhibitor significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with etanercept reduces the development of inflammation and tissue injury events associated with spinal cord trauma.

Authors+Show Affiliations

Genovese T
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina Italy.
Mazzon E
No affiliation info available
Crisafulli C
No affiliation info available
Di Paola R
No affiliation info available
Muià C
No affiliation info available
Bramanti P
No affiliation info available
Cuzzocrea S
No affiliation info available

MeSH

AnimalsApoptosisBlotting, WesternCyclooxygenase 2EtanidazoleImmunologic FactorsInterleukin-1MaleMiceNeutrophil InfiltrationNitric Oxide Synthase Type IIProto-Oncogene Proteins c-bcl-2Spinal Cord InjuriesTumor Necrosis Factor-alphaTyrosinebcl-2-Associated X Protein

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16303916

Citation

Genovese, Tiziana, et al. "Immunomodulatory Effects of Etanercept in an Experimental Model of Spinal Cord Injury." The Journal of Pharmacology and Experimental Therapeutics, vol. 316, no. 3, 2006, pp. 1006-16.
Genovese T, Mazzon E, Crisafulli C, et al. Immunomodulatory effects of etanercept in an experimental model of spinal cord injury. J Pharmacol Exp Ther. 2006;316(3):1006-16.
Genovese, T., Mazzon, E., Crisafulli, C., Di Paola, R., Muià, C., Bramanti, P., & Cuzzocrea, S. (2006). Immunomodulatory effects of etanercept in an experimental model of spinal cord injury. The Journal of Pharmacology and Experimental Therapeutics, 316(3), 1006-16.
Genovese T, et al. Immunomodulatory Effects of Etanercept in an Experimental Model of Spinal Cord Injury. J Pharmacol Exp Ther. 2006;316(3):1006-16. PubMed PMID: 16303916.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunomodulatory effects of etanercept in an experimental model of spinal cord injury. AU - Genovese,Tiziana, AU - Mazzon,Emanuela, AU - Crisafulli,Concetta, AU - Di Paola,Rosanna, AU - Muià,Carmelo, AU - Bramanti,Placido, AU - Cuzzocrea,Salvatore, Y1 - 2005/11/22/ PY - 2005/11/24/pubmed PY - 2006/4/14/medline PY - 2005/11/24/entrez SP - 1006 EP - 16 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 316 IS - 3 N2 - Etanercept is a tumor necrosis factor antagonist with anti-inflammatory effects. The aim of our study was to evaluate for the first time the therapeutic efficacy of in vivo inhibition of tumor necrosis factor-alpha (TNF-alpha) in experimental model of spinal cord trauma, which was 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, and cytokine production that it is followed by recruitment of other inflammatory cells, such as production of a range of inflammation mediators, tissue damage, apoptosis, and disease. Treatment of the mice with etanercept significantly reduced the degree of 1) spinal cord inflammation and tissue injury (histological score); 2) neutrophil infiltration (myeloperoxidase evaluation); 3) inducible nitric-oxide synthase, nitrotyrosine, cyclooxygenase-2, and cytokines expression (TNF-alpha and interleukin-1beta); and 4) apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and Bax and Bcl-2 expression). In a separate set of experiment, we have also clearly demonstrated that TNF-alpha inhibitor significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with etanercept reduces the development of inflammation and tissue injury events associated with spinal cord trauma. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/16303916/Immunomodulatory_effects_of_etanercept_in_an_experimental_model_of_spinal_cord_injury_ DB - PRIME DP - Unbound Medicine ER -