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Combination of dexamethasone and etanercept reduces secondary damage in experimental spinal cord trauma.
Neuroscience. 2007 Nov 30; 150(1):168-81.N

Abstract

The aim of our study was to evaluate the therapeutic efficacy of combination therapy with etanercept and dexamethasone (DEX) in vivo in experimental murine 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 followed by recruitment of other inflammatory cells, production of inflammation mediators, tissue damage, apoptosis and disease. Treatment of the mice with etanercept (1.25 mg/kg) and DEX (0.025 mg/kg) when administered as a combination therapy but not as a single treatment significantly reduced the degree of (1) spinal cord inflammation and tissue injury (histological score), (2) infiltration of neutrophils (MPO evaluation), (3) inducible nitric oxide synthase, nitrotyrosine, and cytokines expression (tumor necrosis factor-alpha and interleukin-1 beta), (4) and apoptosis (Terminal deoxynucleotidyltransferase-mediated UTP end labeling staining, Fas-ligand expression and Bax and Bcl-2 expression). In a separate set of experiments we have also clearly demonstrated that the combination therapy significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate for the first time that strategies targeting multiple proinflammatory pathways may be more effective than a single effector molecule for the treatment of spinal cord trauma.

Authors+Show Affiliations

Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Torre Biologica, Policlinico Universitario Via C. Valeria, Gazzi, 98100 Messina, Italy.No affiliation info availableNo affiliation info availableNo 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

Language

eng

PubMed ID

17945432

Citation

Genovese, T, et al. "Combination of Dexamethasone and Etanercept Reduces Secondary Damage in Experimental Spinal Cord Trauma." Neuroscience, vol. 150, no. 1, 2007, pp. 168-81.
Genovese T, Mazzon E, Crisafulli C, et al. Combination of dexamethasone and etanercept reduces secondary damage in experimental spinal cord trauma. Neuroscience. 2007;150(1):168-81.
Genovese, T., Mazzon, E., Crisafulli, C., Esposito, E., Di Paola, R., Muià, C., Di Bella, P., Meli, R., Bramanti, P., & Cuzzocrea, S. (2007). Combination of dexamethasone and etanercept reduces secondary damage in experimental spinal cord trauma. Neuroscience, 150(1), 168-81.
Genovese T, et al. Combination of Dexamethasone and Etanercept Reduces Secondary Damage in Experimental Spinal Cord Trauma. Neuroscience. 2007 Nov 30;150(1):168-81. PubMed PMID: 17945432.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combination of dexamethasone and etanercept reduces secondary damage in experimental spinal cord trauma. AU - Genovese,T, AU - Mazzon,E, AU - Crisafulli,C, AU - Esposito,E, AU - Di Paola,R, AU - Muià,C, AU - Di Bella,P, AU - Meli,R, AU - Bramanti,P, AU - Cuzzocrea,S, Y1 - 2007/08/02/ PY - 2007/05/24/received PY - 2007/06/11/revised PY - 2007/07/20/accepted PY - 2007/10/20/pubmed PY - 2008/3/29/medline PY - 2007/10/20/entrez SP - 168 EP - 81 JF - Neuroscience JO - Neuroscience VL - 150 IS - 1 N2 - The aim of our study was to evaluate the therapeutic efficacy of combination therapy with etanercept and dexamethasone (DEX) in vivo in experimental murine 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 followed by recruitment of other inflammatory cells, production of inflammation mediators, tissue damage, apoptosis and disease. Treatment of the mice with etanercept (1.25 mg/kg) and DEX (0.025 mg/kg) when administered as a combination therapy but not as a single treatment significantly reduced the degree of (1) spinal cord inflammation and tissue injury (histological score), (2) infiltration of neutrophils (MPO evaluation), (3) inducible nitric oxide synthase, nitrotyrosine, and cytokines expression (tumor necrosis factor-alpha and interleukin-1 beta), (4) and apoptosis (Terminal deoxynucleotidyltransferase-mediated UTP end labeling staining, Fas-ligand expression and Bax and Bcl-2 expression). In a separate set of experiments we have also clearly demonstrated that the combination therapy significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate for the first time that strategies targeting multiple proinflammatory pathways may be more effective than a single effector molecule for the treatment of spinal cord trauma. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/17945432/Combination_of_dexamethasone_and_etanercept_reduces_secondary_damage_in_experimental_spinal_cord_trauma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(07)00815-9 DB - PRIME DP - Unbound Medicine ER -