Effect of 17β-estradiol on signal transduction pathways and secondary damage in experimental spinal cord trauma

Salvatore Cuzzocrea, Tiziana Genovese, Emanuela Mazzon, Emanuela Esposito, Rosanna Di Paola, Carmelo Muià, Concetta Crisafulli, Angelo Peli, Placido Bramanti, Irshad H. Chaudry

Research output: Contribution to journalArticle

Abstract

Because studies have shown that 17β-estradiol (E2) produces anti-inflammatory effects after various adverse circulatory conditions, we examined whether administration of E2 before spinal cord injury (SCI) has any salutary effects in reducing SCI. Spinal cord injury was induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. To gain a better insight into the mechanism of action of the anti-inflammatory effects of E2, the following end points of the inflammatory process were evaluated: (1) spinal cord inflammation and tissue injury (histological score); (2) neutrophil infiltration (myeloperoxidase activity); (3) expression of iNOS, nitrotyrosine, and COX-2; (4) apoptosis (terminal deoxynucleotidyltransferase-mediated UTP end labeling staining and Bax and Bcl-2 expression); and (5) tissue TNF-α, IL-6, IL-1β, and monocyte chemoattractant protein 1 levels. In another set of experiments, the pretreatment or posttreatment with E2 significantly ameliorates the recovery of limb function (evaluated by motor recovery score). To elucidate whether the protective effects of E2 were mediated via the estrogen receptors, we investigated the effect of an estrogen receptor antagonist, ICI 182,780, on the protective effects of E2. ICI 182,780 (500 μg/kg, s.c., 1 h before treatment with E2) significantly antagonized the effect of the E2 and abolished the protective effect against SCI. Taken together, our results clearly demonstrate that administration of E2 before SCI reduces the development of inflammation and tissue injury associated with spinal cord trauma.

Original languageEnglish
Pages (from-to)362-371
Number of pages10
JournalShock
Volume29
Issue number3
DOIs
Publication statusPublished - Mar 2008

Keywords

  • Apoptosis
  • Inflammation
  • SCI
  • Tissue injury

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology

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    Cuzzocrea, S., Genovese, T., Mazzon, E., Esposito, E., Di Paola, R., Muià, C., Crisafulli, C., Peli, A., Bramanti, P., & Chaudry, I. H. (2008). Effect of 17β-estradiol on signal transduction pathways and secondary damage in experimental spinal cord trauma. Shock, 29(3), 362-371. https://doi.org/10.1097/SHK.0b013e31814545dc