Overexpression of cyclooxygenase-2 in rabbit basilar artery endothelial cells after subarachnoid hemorrhage.
OBJECTIVE
We investigated the expression in rabbit basilar arteries of cyclooxygenase (COX)-2, which is the inducible isoform of the enzyme of prostaglandin (PG) production, and the concentrations of the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) and representative PGs in the cerebrospinal fluid (CSF) after experimental subarachnoid hemorrhage (SAH).


METHODS
Seven sets of basilar arteries were removed from control rabbits and from rabbits killed 1 and 3 days after induced SAH. The arteries were subjected to identical simultaneous immunolabeling for examination with a confocal microscope. One-half of each artery was stained for the constitutive form COX-1 and the other half for COX-2. CSF was sampled in control animals and at 6 hours, 1 day, and 3 days for assays of TNFalpha, PGE2, and 6-keto-PGF1 (metabolite of PGI2).


RESULTS
COX-1 immunoreactivity in the endothelial layer was similar in the three groups. Weak endothelial COX-2 immunoreactivity was found in arteries of control animals. COX-2 staining was higher in the group killed at 3 days compared with the control group (P < 0.05). The levels of PGE2 and 6-keto-PGF1alpha in the CSF peaked significantly at 6 hours, then decreased at 3 days to the basal level (PGE2) or significantly lower (6-keto-PGF1). TNFalpha was undetectable in control CSF, significantly higher (P < 0.001) at 6 hours, and undetectable at 3 days.


CONCLUSIONS
After SAH, endothelial COX-1 immunoreactivity does not change, whereas overexpression of COX-2 occurs at 3 days. This induction does not seem linked to TNFalpha production, nor is it responsible for early raised levels of PGE2 and PGI2 in the CSF. We suggest that the role of induced COX-2 may be to modify gene expression and hence alter the properties of the vessel wall after SAH.
Tran Dinh
Y R
YR
Centre National de la Recherche Scientifique UPR 646, IFR6, Université Paris 7, France. yves.tran-dinh@lrb.ap-hop-paris.fr
Jomaa
A
A
Callebert
J
J
Reynier-Rebuffel
A M
AM
Tedgui
A
A
Savarit
A
A
Sercombe
R
R
D000818:Animals; D001488:Basilar Artery / Q000201:enzymology*; D002555:Cerebrospinal Fluid / Q000737:chemistry; D051546:Cyclooxygenase 2; D004730:Endothelium, Vascular / Q000166:cytology* / Q000201:enzymology*; D005786:Gene Expression Regulation; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D010544:Peroxidases / Q000096:biosynthesis*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000201:enzymology*; D013997:Time Factors
D007527:Isoenzymes; D010544:Peroxidases; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases