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.
Hickey
Robert W
RW
Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. robert.hickey@chp.edu
Adelson
P David
PD
Johnnides
Michael J
MJ
Davis
Dwight S
DS
Yu
Zhisheng
Z
Rose
Marie E
ME
Chang
Yue-Fang
YF
Graham
Steven H
SH
D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D018696:Neuroprotective Agents / Q000378:metabolism; D011720:Pyrazoles / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D016861:Cyclooxygenase Inhibitors; D018696:Neuroprotective Agents; D011720:Pyrazoles; C090859:1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole; D051546:Cyclooxygenase 2; D015232:Dinoprostone