Cyclooxygenase-2 Induction in Rat Spinal Cord Injury Mediated By Proinflammatory Tumor Necrosis Factor-α and Interleukin-1
It is well established that the spinal cord is subjected to inflammatory reactions in response to traumatic injury. Several investigators found a major reduction of blood flow in the spinal cord after injury, and vasospasm and thrombosis are considered as major causes of the ischemic insult’. Inflammatory responses underlying the secondary processes are initiated and regulated by specific signaling molecules. Among them vasoactive arachidonate metabolites (eicosanoids) play an important role; proaggregatory and vasoconstrictive thromboxane (TX) A2 as well as antiaggregatory and vasodilating prostaglandin (PG) I22. Cyclooxygenase isozymes (COX-1 and COX-2) are key enzymes, and proinflammatory cytokines like tumor necrosis factor (TNF)-a and interleukin (IL)-1 stimulate the eicosanoid synthesis by the induction of COX-2 in various cell types3,4. Recently, COX-2 induction in the central nervous system was demonstrated in response to seizures5and excitotoxin injection.
KeywordsDexamethasone Prostaglandin Glucocorticoid Neurol Indomethacin
Unable to display preview. Download preview PDF.
- 2.S. Moncada, and J.R.Vane, Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2 and prostacyclinPharmacol. Rev.30:293 (1979).Google Scholar
- 4.W.L. Smith, R.M. Gravito, and D.L. DeWitt, Prostaglandin endoperoxide H synthase (cyclooxygenases)-1 and -2J. Biol. Chem.271:33175 (1996).Google Scholar
- 8.T. Nishisho, T. Tonai, Y. Tamura, and T. Ikata, Experimental and clinical studies of eicosanoids in cerebrospinal fluid after spinal cord injury, Neurosurgery 39:560 (1996).Google Scholar
- 9.T. Tonai, Y. Taketani, U. Ueda, T. Nishish, Y. Ohmoto, Y. Sakata, M. Muraguchi, K. Wada, and S. Yamamoto, Possible involvement of interleukin-1 in cyclooxygenase-2 induction after spinal cord injury in rats, J. Neurochem.72:302(1999).Google Scholar
- 11.M.B. Bracken, M.J. Shepard, W.F. Collins, T.R. Holford, W. Young, D.S. Baskin, H.M. Eisenberg, E. Flamm, L. Leo-Summers, J. Maroon, L.F. Marshall, P.L. Perot Jr., J. Piepmeier, V.K.H. Sonntag, F.C. Wagner, J.E. Wilberger, and H.R. Winn, A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the second national acute spinal cord injury study, N. Engl. J. Med. 322:1405 (1990).Google Scholar