Protective effects of cold spinoplegia with fasudil against ischemic spinal cord injury in rabbits

J Vasc Surg. 2010 Feb;51(2):445-52. doi: 10.1016/j.jvs.2009.10.081.

Abstract

Objective: Paraplegia remains a serious complication after surgical repair of thoracoabdominal aortic aneurysms. The aim of this study was to evaluate the neuroprotective efficacy of fasudil, a Rho kinase (ROCK) inhibitor, by reducing the number of infiltrating cells in the ventral horn and increasing the induction of eNOS against ischemic spinal cord injury in rabbits.

Methods: Eighteen Japanese white rabbits were divided into three groups: saline (group 1, n = 7, 4 degrees C) and fasudil (group 2, n = 6, 4 degrees C) were immediately infused into the isolated segmental lumbar arteries over 30 seconds after aortic clamping. Group 3 (n = 5) was the sham-operated group. Hind limb function was evaluated 4 and 8 hours, and 1 and 2 days after 15 minutes of transient ischemia. Cell damage was analyzed by hematoxylin and eosin staining and temporal profiles of endothelial nitric oxide synthase immunoreactivity were performed. The number of intact motor neuron cells and infiltrating cells in the ventral horn were compared.

Results: Two days after reperfusion, group 2 and group 3 showed better neurologic function, a greater number of intact motor neuron cells, and a smaller number of infiltrating cells in the ventral horn than group 1. The induction of endothelial nitric oxide synthase (eNOS) was prolonged up to 2 days after reperfusion in group 2.

Conclusion: These results indicate that fasudil has neuroprotective effects against ischemic spinal cord injury in rabbits by reducing the number of infiltrating cells in the ventral horn and prolonging the expression of eNOS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / administration & dosage
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Animals
  • Anterior Horn Cells / drug effects*
  • Anterior Horn Cells / enzymology
  • Anterior Horn Cells / pathology
  • Aorta / surgery
  • Constriction
  • Disease Models, Animal
  • Enzyme Induction
  • Hypothermia, Induced*
  • Immunohistochemistry
  • Infusions, Intra-Arterial
  • Male
  • Motor Activity / drug effects
  • Neurologic Examination
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Nitric Oxide Synthase Type III / biosynthesis
  • Paraplegia / enzymology
  • Paraplegia / prevention & control
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacology*
  • Rabbits
  • Spinal Cord Injuries / enzymology
  • Spinal Cord Injuries / physiopathology
  • Spinal Cord Injuries / prevention & control*
  • Spinal Cord Ischemia / enzymology
  • Spinal Cord Ischemia / physiopathology
  • Spinal Cord Ischemia / prevention & control*
  • Time Factors
  • rho-Associated Kinases / antagonists & inhibitors*
  • rho-Associated Kinases / metabolism

Substances

  • Neuroprotective Agents
  • Protein Kinase Inhibitors
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Nitric Oxide Synthase Type III
  • rho-Associated Kinases
  • fasudil