Selective cyclooxygenase 2 inhibition lowers spinal cord prostaglandin concentrations after injury.
BACKGROUND
Prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) concentrations are elevated in the injured spinal cord for hours to days after injury. Treatment of animals with a selective cyclooxygenase-2 (COX-2) inhibitor has been shown to improve functional outcome in an animal model.


OBJECTIVE
We sought to characterize the effects of COX-2 inhibition on prostaglandin concentrations in the spinal cord after injury.


METHODS
A drug study was performed using 76 male Long Evans rats.


METHODS
PGE2 and TxB2 concentrations were measured by enzyme immune assay.


METHODS
Fifty-six rats were subject to spinal cord injury, and 4 rats served as sham controls. Twenty eight rats received 3 mg/kg of celebocid by means of an orogastric tube within 20 minutes after injury, and 28 received vehicle alone. The animals were sacrificed at time points between 2 and 72 hours after injury, and PGE2 and TxB2 levels were measured. A second study was performed using transcardiac saline perfusion in order to reduce intragroup variance in measured PGE2 and TxB2 levels. Sixteen animals underwent spinal cord injury. Animals were sacrificed at 4 and 24 hours after injury, and PGE2 and TxB2 levels were measured.


RESULTS
PGE2 and TxB2 concentrations were elevated after injury in all animals. Administration of celebocid resulted in a delayed reduction of PGE2 and TxB2 concentrations in the initial drug study. These results were not statistically significant. Transcardiac perfusion with normal saline reduced the intragroup variance. Using this technique, administration of celebocid resulted in a statistically significant reduction in PGE2 and TxB2 concentrations in the injured cord segment 4 and 24 hours after injury.


CONCLUSIONS
Administration of a selective COX-2 inhibitor after injury results in a decrease of PGE2 and TxB2 concentrations in the injured spinal cord. Transcardiac perfusion after sacrifice reduces measured variance, probably through reducing the contribution of blood-borne prostaglandins.
Resnick
D K
DK
Department of Neurological Surgery, University of Wisconsin School of Medicine, K4/834 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792, USA. Resnick@neurosurg.wisc.edu
Nguyen
P
P
Cechvala
C F
CF
D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004195:Disease Models, Animal; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases; D051381:Rats; D020318:Rats, Long-Evans; D013116:Spinal Cord / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013929:Thromboxane B2; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone