Role of Prostacyclin in the Development of Compression Trauma-Induced Spinal Cord Injury in Rats

Abstract

We investigated the role of prostacyclin (PGI₂) in the development of compression trauma–induced spinal cord injury (SCI) in rats. When measured after induction of SCI, tissue levels of 6-keto-PGF_1α, a stable PGI₂ metabolite, thromboxane B₂ (TXB₂), a stable metabolite of thromboxane A₂, myeloperoxidase (MPO) activity, and tumor necrosis factor (TNF) in the injured spinal cord segment were significantly increased, peaking at 2, 3, and 4 h after induction of SCI, respectively. Subcutaneous administration of indomethacin (IM), a non-selective cyclooxygenase (COX) inhibitor, completely inhibited increases in tissue levels of 6-keto-PGF_1α and TXB₂, while administration of NS-398, a selective inhibitor of COX-2, did not affect these increases. Although pretreatment with IM enhanced increases in tissue levels of MPO, TNF, and TNF mRNA and exacerbated both motor disturbances and histological damage in the spinal cord of animals subjected to SCI, pretreatment with NS-398 had no effect on any of these findings. Both iloprost, a stable analog of PGI₂, and leukocyte depletion significantly reversed changes in various variables and exacerbation of motor disturbances induced by IM pretreatment in animals subjected to SCI. These observations strongly suggested that compression trauma–induced increase in PGI₂ production in spinal cord tissue might be mainly mediated by COX-1 and PGI₂ might play a critical role in reduction of motor disturbances following SCI by inhibiting neutrophil accumulation through inhibition of TNF production.