Overexpression of cyclooxygenase-2 in rabbit basilar artery endothelial cells after subarachnoid hemorrhage

OBJECTIVE: We investigated the expression in rabbit basilar arteries of cyc looxygenase (COX)-2, which is the inducible isoform of the enzyme of prosta glandin (PC) production, and the concentrations of the proinflammatory cyto kine tumor necrosis factor alpha (TNF alpha) and representative PGs in the cerebrospinal fluid (CSF) after experimental subarachnoid hemorrhage (SAH). METHODS: Seven sets of basilar arteries were removed from control rabbits a nd from rabbits killed 1 and 3 days after induced SAH. The arteries were su bjected to identical simultaneous immunolabeling for examination with a con focal 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 TNF alpha, PGE(2), and 6-k eto-PGF(1) (metabolite of PGI(2)). RESULTS: COX-1 immunoreactivity in the endothelial layer was similar in the three groups. Weak endothelial COX-2 immunoreactivity was found in arterie s of control animals. COX-2 staining was higher in the group killed at 3 da ys compared with the control group (P < 0.05). The levels of PGE(2) and 6-k eto-PGF(1<alpha>) in the CSF peaked significantly at 6 hours, then decrease d at 3 days to the basal level (PGE(2)) or significantly lower (6-keto-PGF( 1)). TNF alpha was undetectable in control CSF, significantly higher (P < 0 .001) at 6 hours, and undetectable at 3 days. CONCLUSION: After SAH, endothelial COX-1 immunoreactivity does not change, whereas overexpression of COX-2 occurs at 3 days. This induction does not s eem linked to TNF<alpha> production, nor is it responsible for early raised levels of PGE(2) and PGI(2) in the CSF. We suggest that the role of induce d COX-2 may be to modify gene expression and hence alter the properties of the vessel wall after SAH.