Selective inhibition of cyclooxygenase-2 attenuates expression of inflammation-related genes in CNS injury models

Abstract

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.