Role of prostacyclin in the development of compression trauma-induced spinal cord injury in rats.
We investigated the role of prostacyclin (PGI(2)) 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(1), a stable PGI(2) metabolite, thromboxane B(2) (TXB(2)), a stable metabolite of thromboxane A(2), 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(1) and TXB(2), 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 PGI(2), 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 PGI(2) production in spinal cord tissue might be mainly mediated by COX-1 and PGI(2) might play a critical role in reduction of motor disturbances following SCI by inhibiting neutrophil accumulation through inhibition of TNF production.
Harada
Naoaki
N
Department of Biodefense Medicine, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
Taoka
Yuji
Y
Okajima
Kenji
K
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000031:analogs & derivatives*; D016285:Iloprost / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D020556:Neutrophil Infiltration / Q000187:drug effects*; D009578:Nitrobenzenes / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology*; D013449:Sulfonamides / Q000494:pharmacology; D013904:Thoracic Vertebrae; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D012333:RNA, Messenger; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D011464:Epoprostenol; D016285:Iloprost; D007213:Indomethacin