Effect of indomethacin on motor activity and spinal cord free fatty acid content after experimental spinal cord injury in rabbits

Spinal Cord. 2005 Sep;43(9):519-26. doi: 10.1038/sj.sc.3101763.

Abstract

Study design: Determination of functional and biochemical parameters as well as the effect of specific therapies on these parameters, in the experimental model of neurotrauma in rabbits.

Objective: To assess the effect of indomethacin (0.1-3.0 mg/kg for 9 days), a potent inhibitor of endogenous prostaglandin synthesis, on the motor activity and on the spinal cord tissue concentration of free palmitic, stearic, oleic, arachidonic and docosahexaenoic acids in an experimental model of a spinal cord injury in rabbits.

Setting: Faculty of Medicine, University of Rijeka, Croatia.

Methods: The animals were randomly divided into nine experimental groups, four sham and/or vehicle-treated and five indomethacin-treated (including one sham-operated and four injured groups). Laminectomy was followed by contusion of the spinal cord, using a modification of the technique of Albin. Motor activity was controlled daily during the course of the next nine postoperation days and scored using Tarlov's system. Spinal cord samples from the impact injury site were taken and frozen in liquid nitrogen. Total lipids were isolated and purified by a modification of the method of Folch. Free fatty acids (FFAs) were separated from the total lipid extract by preparative thin-layer chromatography, converted to the corresponding methyl esters and identified using gas chromatography, using nonadecanoic acid as the internal standard.

Results: The concentrations of all analysed free fatty acids were increased in the spinal cord after neurotrauma, in comparison to control tissues. Treatment of injured rabbits with indomethacin resulted in a significant decrease in spinal cord FFAs and exerted a positive effect on neurotrauma-induced motor impairment.

Conclusion: These results indicate a mechanism whereby indomethacin protects rabbits from the sequellae of neuronal damage caused by trauma, and suggests that it may be beneficial in the therapy of neurotrauma.

Sponsorship: This work was supported by the Croatian Ministry of Science and Technology (project 062019).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Fatty Acids, Nonesterified / metabolism*
  • Indomethacin / therapeutic use*
  • Motor Activity / drug effects*
  • Paraplegia / etiology
  • Paraplegia / physiopathology*
  • Paraplegia / prevention & control*
  • Rabbits
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism*
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / physiopathology*
  • Treatment Outcome

Substances

  • Fatty Acids, Nonesterified
  • Indomethacin