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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., Conclusion: 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.

Experiments were performed to test the hypothesis that subarachnoid hemorrhage (SAH) causes functionally relevant perturbations of cyclooxygenase activity in cerebral arteries. Four groups of rabbits were formed: (I) controls; (II) sham injected animals (2 ml physiological solution in the cisterna magna); (III) SAH group (2 ml blood in cisterna magna); (IV) indomethacin group (4 mg/kg i.v. 30 min before sacrifice). Animals of groups II and III were used 3 days after injection. The basilar arteries (BAs) were removed and perfused at a constant flow rate (after electrocoagulation of all branches) in vitro in a 2-ml bath at 37 degrees C. After 45 min equilibration, the arteries were subjected to a fixed protocol: first, in Krebs solution, contraction to increasing extraluminal concentrations of histamine (HA), followed by a single maximal extraluminal concentration of acetylcholine (ACh); then, after 30 min rest, the same tests were repeated in oxyhemoglobin (oxyHb) solution (extraluminal, 10-4 M). Perfusion pressure changes reflected changes in artery resistance. Although oxyHb alone increased pressure, indicating contraction of the arteries, its most important effect was to increase contraction to HA (in groups II, III, and IV but not controls) and to strongly inhibit ACh-induced relaxation in the SAH (-66.3%) and indomethacin (-46.9%) groups (III and IV) but not the control (-27.6%) group. The latter result suggests that a relaxing factor released by ACh in oxyHb solution in the control group was not present in groups III and IV. In conjunction with the results on HA, which is known to normally release prostacyclin (PGI2) from the endothelium, it is concluded that PGI2 was not or little released from arteries of the SAH group when they bathed in oxyHb solution. Alternatively, in the SAH group constrictor prostaglandins were released in response to HA and ACh in place of PGI2., (Copyright 1998 Elsevier Science B.V.)