Role of cyclooxygenase 2 in acute spinal cord injury

Cyclooxygenase, or prostaglandin G/H synthase, is the rate-limiting step in the production of prostaglandins. A new isoform, cyclooxygenase-2 (COX-2), has been cloned that is induced during inflammation in leukocytes and by s ynaptic activity in neurons. The objectives of this study are to determine the nature of COX-2 expression in normal and traumatized rat spinal cord, a nd to determine the effects of selective COX-2 inhibition on functional rec overy following spinal cord injury. Using a weight-drop model of spinal cor d injury, COX-2 mRNA expression was studied with in situ hybridization, COX -2 protein expression was examined by immunohistochemistry and Western anal ysis. Finally, using the highly selective COX-2 inhibitor, 1-[(4-methylsufo nyl)phenyl]-3-tri-fluro-methyl-5-[(4-fluro)phenyl]prazole (SC58125), the ef fect of COX-2 inhibition on functional outcome following a spinal cord inju ry was determined. COX-2 was expressed in the normal adult rat spinal cord. COX-2 mRNA and protein production were increased following injury with inc reases in COX-2 mRNA production detectable at 2 h following injury. Increas ed levels of COX-2 protein were detectable for at least 48 h following trau matic spinal cord injury. Selective inhibition of COX-2 activity with SC581 25 resulted in improved mean Basso, Beattie, and Bresnahan scores in animal s with 12.5- and 25-g/cm spinal cord injuries; however, the effect was sign ificant only for the 12.5-g/cm injury group (p = 0.0001 vs. p = 0.0643 in t he 25-g/cm group). These data demonstrate that COX-2 mRNA and protein expre ssion are induced by spinal cord injury, and that selective inhibition of C OX-2 improves functional outcome following experimental spinal cord injury.