Cyclooxygenase-2 activity following traumatic brain injury in the developing rat.

Cyclooxygenase (COX) is the rate-limiting enzyme in the production of prostaglandins. COX-2, the predominant COX isoform in brain, is induced by synaptic activity. COX-2-generated prostaglandins are important regulators for a range of activities under physiologic conditions. However, under pathologic conditions, COX-2 activity can produce reactive oxygen species and toxic prostaglandin metabolites that can exacerbate brain injury. In this study, we examine the developmental production of COX-2 and test the ability of a COX-2 inhibitor, SC58125, to attenuate traumatic brain injury in developing rats. We show that constitutive COX-2 concentration is low (0.5-fold adult concentration) during the first postnatal week and then increases to 3-fold of adult levels between days 14-60. Controlled cortical impact (CCI) at postnatal day (PND) 17, but not PND 7, caused an additional 3-fold increase in COX-2 content and was associated with an increase in the COX-2 product PGE2. Treatment with the COX-2 inhibitor SC58125 in PND17 rats exposed to CCI attenuated the rise in PGE2 but did not attenuate lesion volume or improve performance in the Morris water maze.