Selective Inhibition of Cyclooxygenase-2 Attenuates Expression of Inflammation-Related Genes in Cns Injury

  • M. Kerry O’Banion
  • Stephanos Kyrkanides
  • John A. Olschowka
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 507)


Injury to the brain, whether arising from trauma, stroke, or infection, elicits a tissue response characterized by glial cell activation and production of inflammation-related gene products. A similar response occurs in Alzheimer’s disease, where deposits of amyloid-beta are associated with activated glia and a wide variety of inflammatory products have been detected (Neuroinflammation Working Group, 2000). The widespread use of glucocorticoids in spinal cord injury and epidemiological evidence that nonsteroidal anti-inflammatory drugs may be beneficial in Alzheimer’s disease indicate that therapies targeting inflammatory processes may be useful in treatment of central nervous system (CNS) injury and disease. Cyclooxygenase-2 (COX-2) plays a major role in peripheral inflammatory processes (Dubois et al., 1998). Tissue culture studies show that astrocytes and microglia have the capacity to express COX-2 in response to proinflammatory cytokines (O’Banion et al., 1996; O’Banion, 1999). However, little is known about the contribution of COX-2 to inflammatory processes in the CNS.


Traumatic Brain Injury Central Nervous System Injury Glial Activation Tissue Culture Study Glial Cell Activation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Balasingam, V., Dickson, K., Brade, A. and Yong, V.W., 1996, Astrocyte reactivity in neonatal mice: apparent dependence on the presence of reactive microglia/macrophages, Glia 18:11.PubMedCrossRefGoogle Scholar
  2. 2.
    Borriello, F. and Lederer, J., 1995, Construction of RT-PCR mimics, Biotechniques 19:580.PubMedGoogle Scholar
  3. 3.
    Dash, P.K., Mach, S.A. and Moore, A.N., 2000, Regional expression and role of cyclooxgyenase-2 following experimental traumatic brain injury, J. Neurotrauma 17:69.PubMedCrossRefGoogle Scholar
  4. 4.
    Dubois, R.N., Abramson, S.B., Crofford, L., Gupta, R.A., Simon, L.S., van de Putte, L.B.A. and Lipsky, P.E., 1998, Cyclooxygenase in biology and disease, FASEB J. 12:1063.PubMedGoogle Scholar
  5. 5.
    Futaki, N., Takahashi, S., Yokoyama, M., Arai, I., Higuchi, S. and Otomo, S., 1994, NS-398, a new anti-inflammatory agent, selectively inhibits prostaglandin G/H synthase/cyclooxygenase (COX-2) activity in vitro, Prostaglandins 47:55.PubMedCrossRefGoogle Scholar
  6. 6.
    Gilroy, D.W., Colville-Nash, P.R., Willis, D., Chivers, J., Paul-Clarke, M.J. and Willoughby, D.A., 1999, Inducible cyclooxygenase may have anti-inflammatory properties, Nature Med. 5:698.PubMedCrossRefGoogle Scholar
  7. 7.
    Kyrkanides, S., Olschowka, J.A., Williams, J.P., Hansen, J.T. and O’Banion, M.K., 1999, TNFa and IL-lß mediate intercellular adhesion molecule-1 induction via microglia-astrocyte interaction in CNS injury, J. Neuroimmunol. 95:95.PubMedCrossRefGoogle Scholar
  8. 8.
    Mathewson, A.J. and Berry, M., 1985, Observations on the astrocytic response to a cerebral stab wound in adult rats, Brain Res. 327:61.PubMedCrossRefGoogle Scholar
  9. 9.
    Neuroinflammation Working Group, 2000, Inflammation and Alzheimer’s Disease, Neurobiol. Aging In Press.Google Scholar
  10. 10.
    Nogawa, S., Zhang, F., Ross, M.E. and Iadecola, C., 1997, Cyclooxygenase-2 gene expression in neurons contributes to ischemic brain damage, J. Neurosci. 17:2746.PubMedGoogle Scholar
  11. 11.
    Norton, W.T., Aquino, D.A., Hozumi, I., Chiu, F.-C. and Brosnan, C.F., 1992, Quantitative aspects of reactive gliosis: a review, Neurochem. Res. 17:877.PubMedCrossRefGoogle Scholar
  12. 12.
    O’Banion, M.K., 1999, Cyclooxygenase-2: molecular biology, pharmacology, and neurobiology, Crit. Rev. Neurobiol. 13:45.PubMedGoogle Scholar
  13. 13.
    O’Banion, M.K., Dusel, J.C., Chang, J.W., Kaplan, M.D. and Coleman, P.D., 1996, Interleukin-lß induces prostaglandin G/H synthase-2 (cyclooxygenase-2) in primary murine astrocyte cultures, J. Neurochem. 66:2532.PubMedCrossRefGoogle Scholar
  14. 14.
    Olschowka, J.A., Kyrkanides, S., Harvey, B.K., O’Banion, M.K., Williams, J.P., Rubin, P. and Hansen, J.T., 1997, ICAM-1 induction in the mouse CNS following irradiation, Brain Behay. Immunol. 11:273.CrossRefGoogle Scholar
  15. 15.
    Peri, K.G., Hardy, P., Li, D.Y., Varma, D.R. and Chemtob, S., 1995, Prostaglandin G/H synthase-2 is a major contributor of brain prostaglandins in the newborn, J. Biol. Chem. 270:24615.PubMedCrossRefGoogle Scholar
  16. 16.
    Perry, V.H., Hume, D.A. and Gordon, S., 1985, Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain, Neuroscience 15:313.PubMedCrossRefGoogle Scholar
  17. 17.
    Topp, K.S., Faddis, B.T. and Vijayan, V.K., 1989, Trauma-induced proliferation of astrocytes in the brains of young and aged rats, Glia 2:201.PubMedCrossRefGoogle Scholar
  18. 18.
    Yamagata, K., Andreasson, K.I., Kaufmann, W.I., Barnes, C.A. and Worley, P.F., 1993, Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids, Neuron 11:371.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • M. Kerry O’Banion
    • 1
    • 2
  • Stephanos Kyrkanides
    • 2
    • 3
  • John A. Olschowka
    • 2
  1. 1.Department of NeurologyUniversity of Rochester School of Medicine and DentistryRochesterUSA
  2. 2.Department of Neurobiology & AnatomyUniversity of Rochester School of Medicine and DentistryRochesterUSA
  3. 3.Eastman Department of DentistryUniversity of Rochester School of Medicine and DentistryRochesterUSA

Personalised recommendations