Effects of COX-2 and iNOS inhibitors alone or in combination with olfactory ensheathing cell grafts after spinal cord injury.

Abstract

We studied the effects of inhibitors of COX-2 (NS398) and iNOS (aminoguanidine) alone or in combination with olfactory ensheathing cell (OEC) grafts after spinal cord injury in the rat. To assess the role exerted by COX-2 and iNOS after spinal cord injury and an OEC transplant. COX-2 and iNOS exert a detrimental effect after spinal cord injury. In contrast, OECs grafted into the injured spinal cord mediate neuroprotection and also promote the up-regulation of COX-2 and iNOS. Photochemical injury was induced at T8 spinal cord segment. Rats received local injection of OECs (n = 15) or vehicle (DMEM; n = 15). Six subgroups of rats (n = 5 rats each) were given NS398 (DM-NS; OEC-NS), aminoguanidine (DM-AG; OEC-AG), or saline (DM-SS; OEC-SS). Locomotor ability, pain sensibility, tissue sparing, and density of blood vessels were evaluated. Two weeks following injury, motor skills and nociceptive response were significantly higher in DM-NS and DM-AG than in DM-SS rats. The area of preserved spinal cord parenchyma was higher in treated animals than in those given saline. In contrast, functional outcome, tissue sparing, and density of blood vessels were lower in OEC-NS and OEC-AG than in OEC-SS animals. These results suggest that, although COX-2 and iNOS exert a detrimental role after spinal cord injury, they may play an important role in the neuroprotective mechanisms induced by OEC grafts after spinal cord injury.