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

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.

Mapping Lipid Alterations in Traumatically Injured Rat Spinal Cord by Desorption Electrospray Ionization Imaging Mass Spectrometry

“…The species resulting from the hydrolysis of phospholipids, due to the production of enzyme PLA 2 during the SCI, can still be detected in the samples one week after the injury. This result slightly differs from the literature where the increase of FFAs and DG is followed by a decline around 10h after the SCI, even if time points later than 24h were not studied 69, 70, 73, 74. However, a recent MALDI mass spectrometry imaging study has revealed the production of lysophosphatidylcholine in the injured ischemic rat brain 48h after the MCA occlusion 95.…”

Ibuprofen Enhances Recovery from Spinal Cord Injury by Limiting Tissue Loss and Stimulating Axonal Growth

“…1a). Interestingly, indomethacin, an NSAID that has been tested in several SCI studies with minimal benefit (Guven et al, 1999;Pantovic et al, 2005;Schwab et al, 2004), does not block Rho signaling in our in vitro studies.…”

Small-molecule-induced Rho-inhibition: NSAIDs after spinal cord injury

“…Conversely, no significant changes in the motor score have been observed at 4 weeks after SCI in indomethacin-treated rats after spinal cord compression (Guth et al 1994). In a rabbit model of spinal cord contusion, animals treated daily with indomethacin starting immediately after injury have been reported to have a better motor score function visible from day 1 to the end of the observation at day 9 after SCI (Pantovic et al 2005). These early treatment effects on motor function have not been observed in the rodent trials published for NSAID treatment after SCI.…”