Effect of fasudil, a selective inhibitor of rho kinase activity, in the secondary injury associated with the experimental model of spinal cord trauma

Daniela Impellizzeri, Emanuela Mazzon, Irene Paterniti, Emanuela Esposito, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

Abstract

Rho kinase (ROK) may play an important role in regulating the biological events of cells, including proliferation, differentiation, and survival/death. Blockade of ROK promotes axonal regeneration and neuron survival in vivo and in vitro, thereby exhibiting potential clinical applications in spinal cord damage and stroke. The aim of this experimental study was to determine the role of ROK signaling pathways in the inflammatory response, in particular in the secondary injury associated with the experimental model of spinal cord trauma. The injury was induced by application of vascular clips to the dura via a four-level T5 to T8 laminectomy in mice. Fasudil was administered in mice (10 mg/kg i.p.) 1 and 6 h after the trauma. The treatment with fasudil significantly decreased 1) histological damage; 2) motor recovery; 3) nuclear factor-κB (NF-κB) expression; 4) ROK activity; 5) inflammasome activation (caspase-1 and NOD-like receptor family, pyrin domain-containing 3 expression); 6) production of proinflammatory cytokine such as tumor necrosis factor and interleukin-1β (IL-1β); 7) neutrophil infiltration; 8) nitrotyrosine and poly-ADP-ribose formation; 9) glial fibrillary acidic protein expression; 10) apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, FAS ligand expression, and Bax and Bcl-2 expression); and 11) mitogen-activated protein kinase activation (phospho-extracellular signal-regulated kinase and phospho-c-Jun NH2-terminal kinase expression). Our results indicate that inhibition of ROK by fasudil may represent a useful therapeutic perspective in the treatment of inflammation associated with spinal cord trauma.

Original languageEnglish
Pages (from-to)21-33
Number of pages13
JournalJournal of Pharmacology and Experimental Therapeutics
Volume343
Issue number1
DOIs
Publication statusPublished - Oct 2012

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ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

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