Experimental and Clinical Studies of Eicosanoids in Cerebrospinal Fluid after Spinal Cord Injury

Abstract

OBJECTIVE: In an attempt to elucidate a possible role for eicosanoids in the pathogenesis of spinal cord injury (SCI), we measured the concentration of leukotriene (LT) C4, thromboxane B2, and 6-keto-prostaglandin F1α in cerebrospinal fluid in both a canine experimental model and 11 patients with SCIs. METHODS: The eicosanoid concentration in cerebrospinal fluid was measured by radioimmunoassay. Neurological severity was assessed according to the grading system of Frankel et al. (11). Control samples were obtained from 20 patients without SCIs. RESULTS: In the canine model, a significant increase in all eicosanoid levels was found on Days 1 to 7, which subsequently returned to the control levels. In the clinical study, the highest mean (± standard error of the mean) concentrations of LTC4, thromboxane B2, and 6-keto-prostaglandin F1α in the acute stage of SCI were 95.9 ± 10.7, 175.2± 38.2, and 167.5 ± 39.9 pg/ml, respectively. These concentrations were five to nine times higher than control levels. There was a good correlation between cerebrospinal fluid LTC4 levels and the neurological severity. The time-dependent change in LTC4 concentrations in seven patients with SCIs was similar to that observed in the canine model. In addition, the highest mean concentrations of the eicosanoids measured in patients with complete paralysis was also similar to those of the canine model. The eicosanoid concentrations in five patients with SCI were measured more than 6 months after the onset of injury. Although all eicosanoid levels had elevated in the acute stage of injury, they were not elevated and showed the same levels as the controls at the chronic stage. CONCLUSION: The findings suggest that enhanced arachidonate metabolism occurs in humans and support the evidence from animal experiments that emphasizes the importance of eicosanoids in the secondary processes mediating ischemia and edema.