A non-enzymatic derived arachidonyl peroxide, 8-iso-prostaglandin F2α, in cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage participates in the pathogenesis of delayed cerebral vasospasm

We performed serial measurements of 8-iso-prostaglandin F2α (8-iso-PGF2α), a non-enzymatic derived arachidonyl peroxide, in the cerebrospinal fluid (CSF) of 34 patients with subarachnoid hemorrhage (SAH). Patients were treated with open or endovascular surgery within 48 h of onset. Delayed cerebral vasospasm was verified by the presence of a low-density area on CT scan indicating focal cerebral infarction occurring after symptomatic delayed vasospasm. Concentrations of 8-iso-PGF2α in the CSF of 15 patients exhibiting delayed cerebral vasospasm were compared with those of 19 patients who did not exhibit vasospasm. The concentrations of 8-iso-PGF2α in the CSF of patients showing vasospasm were 42.4 ± 37.1 pg/ml (mean ± S.D., n = 12) on Days 0-2, 66.4 ± 41.0 pg/ml (n = 14) on Days 3-5, 118.5 ± 89.9 pg/ml (n = 15) on Days 6-8, 86.2 ± 70.2 pg/ml (n = 11) on Days 9-11, 48.8 ± 31.8 pg/ml (n = 10) on Days 12-14, 27.8 ± 20.1 pg/ml (n = 7) after Day 20, while the concentrations in patients not showing vasospasm were 24.8 ± 12.0 pg/ml (n = 18) on Days 0-2, 25.7 ± 15.2 pg/ml (n = 19) on Days 3-5, 47.5 ± 52.3 pg/ml (n = 18) on Days 6-8, 56.7 ± 72.0 pg/ml (n = 13) on Days 9-11, 34.2 ± 53.1 pg/ml (n = 15) on Days 12-14, 20.1 ± 18.2 pg/ml (n = 10) after Day 20. CSF concentrations of 8-iso-PGF2α on Days 3-5 and Days 6-8 were significantly higher in patients showing vasospasm as compared to patients not showing vasospasm. CSF levels of 8-iso-PGF2α in patients showing vasospasm gradually increased in the days after onset of SAH and peaked on Days 6-8. Levels returned to normal after Day 20. These values on Days 3-5, Days 6-8, and Days 9-11 were significantly higher than the value after Day 20. Considering these data and the biological activities of 8-iso-PGF2α, such as development of inflammation, membrane perturbation and vasoconstriction, we conclude that 8-iso-PGF2α may play a role in delayed cerebral vasospasm after SAH.