Regional expression and role of cyclooxygenase-2 following experimental traumatic brain injury.
Prostaglandins, potent mediators of inflammation, are generated from arachidonic acid (AA) via the action of cyclooxygenase-1 and -2 (COX-1 and COX-2). In this study, we report that lateral cortical impact injury in rats significantly increases COX-2 protein levels both in the cortex surrounding the injury site and the ipsilateral hippocampus. COX-2 protein level was elevated as early as 3 h postinjury and persisted for up to 3 days. Increases in immunoreactivity were detected not only in the adjacent cortex and hippocampus, but were also observed in the contralateral cortex and hippocampus, the ipsilateral piriform cortex and the ipsilateral amygdaloid complex. COX-2 immunoreactive cells appear morphologically normal and do not present any of the characteristic features of apoptosis. Double immunostaining experiments using either a neuron-specific or an astroglial-specific marker show that the expression of COX-2 is localized almost exclusively in neuronal cells. Administration of the COX-2 inhibitor 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfona mide (celecoxib, marketed as Celebrex) worsens motor, but not cognitive, performance, suggesting that COX-2 induction following traumatic brain injury may play a protective role.
Dash
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Department of Neurobiology and Anatomy, University of Texas Medical School, Houston 77225, USA. pdash@nba19.med.uth.tmc.edu
Mach
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Moore
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D000679:Amygdala / Q000201:enzymology / Q000293:injuries / Q000473:pathology; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D000068579:Celecoxib; D002540:Cerebral Cortex / Q000201:enzymology* / Q000293:injuries / Q000473:pathology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000201:enzymology* / Q000293:injuries / Q000473:pathology; D007527:Isoenzymes / Q000096:biosynthesis* / Q000494:pharmacology / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009048:Motor Skills / Q000187:drug effects; D009460:Neurologic Examination; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D009833:Olfactory Pathways / Q000201:enzymology / Q000293:injuries / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000494:pharmacology / Q000502:physiology; D011720:Pyrazoles; D051381:Rats; D020318:Rats, Long-Evans; D013449:Sulfonamides / Q000494:pharmacology; D014949:Wounds, Nonpenetrating / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib