Immunomodulatory effects of etanercept in an experimental model of spinal cord injury

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

Research output: Contribution to journalArticlepeer-review

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-α(TNF-α) 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 T 5-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-α and interleukin-1β); 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-α 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.

Original languageEnglish
Pages (from-to)1006-1016
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume316
Issue number3
DOIs
Publication statusPublished - Mar 2006

ASJC Scopus subject areas

  • Pharmacology

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