Rho kinase (ROK) may play an important role in regulating 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-T8 laminectomy in mice. Fasudil was administered in mice (10 mg/kg i.p.) 1 h and 6 h after the trauma. The treatment with fasudil significantly decreased (1) histological damage, (2) motor recovery, 3) nuclear factor (NF)-κB expression, (4) pro-inflammatory cytokines production such as Tumor Necrosis Factor (TNF-α) and Interleuchin-1β] (IL-1β]), (5) neutrophil infiltration, (6) nitrotyrosine and poly-ADP-ribose (PAR) formation, (7) Glial fibrillary acidic protein (GFAP) expression, (8) apoptosis (TUNEL staining, FAS ligand expression, Bax and Bcl-2 expression), (9) MAP Kinase activation (P-ERK and P-JNK 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.
- Received December 22, 2011.
- Revision received June 22, 2012.
- Accepted June 22, 2012.
- The American Society for Pharmacology and Experimental Therapeutics