EXPERIMENTAL AND CLINICAL-STUDIES OF EICOSANOIDS IN CEREBROSPINAL-FLUID AFTER SPINAL-CORD INJURY

OBJECTIVE: In an attempt to elucidate a possible role for eicosanoids in the pathogenesis of spinal cord injury (SCI), we measured the conce ntration of leukotriene (LT) C-4, thromboxane B-2, and 6-keto-prostagl andin F-1 alpha in cerebrospinal fluid in both a canine experimental m odel 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, R ESULTS: in the canine model, a significant increase in all eicosanoid levels was found on Days 1 to 7, which subsequently returned to the co ntrol levels. In the clinical study, the highest mean (+/- standard er ror of the mean) concentrations of LTC(4), thromboxane B-2, and 6-keto -prostaglandin F-1 alpha in the acute stage of SCI were 95.9 +/- 10.7, 175.2 +/- 38.2, and 167.5 +/- 39.9 pg/ml, respectively. These concent rations were five to nine times higher than control levels. There was a good correlation between cerebrospinal fluid LTC, levels and the neu rological severity. The time-dependent change in LTC, concentrations i n 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 thos e of the canine model. The eicosanoid concentrations in five patients with SCI were measured more than 6 months after the onset of injury. A lthough all eicosanoid levels had elevated in the acute stage of injur y, they were not elevated and showed the same levels as the controls a t the chronic stage. CONCLUSION: The findings suggest that enhanced ar achidonate metabolism occurs in humans and support the evidence from a nimal experiments that emphasizes the importance of eicosanoids in the secondary processes mediating ischemia and edema.