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

Abstract

We performed serial measurements of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), 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-PGF2alpha 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-PGF2alpha 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-PGF2alpha 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-PGF2alpha 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-PGF2alpha, such as development of inflammation, membrane perturbation and vasoconstriction, we conclude that 8-iso-PGF2alpha may play a role in delayed cerebral vasospasm after SAH.

Are Isofurans and Neuroprostanes Increased After Subarachnoid Hemorrhage and Traumatic Brain Injury?

“…F 2 -IsoPs were also significantly higher in aSAH patients who developed delayed onset cerebral vasospasm (1). Asaeda et al (1) showed that F 2 -IsoPs increased during the period of peak vasospasm and decreased gradually thereafter. The authors suggested that increased CSF F 2 -IsoPs derived from the subarachnoid clot could be one of the causes of delayed cerebral vasospasm after aSAH.…”

The pathophysiology and treatment of delayed cerebral ischaemia following subarachnoid haemorrhage

“…Human data indicates an increase in oxidative stress and lipid peroxidation in serum as well as CSF within 3 days after SAH 115 118 119 120. Furthermore, the increases are more pronounced in patients who developed DCI115 116 and those with poor neurological outcome 119 120. Markers of CSF lipid peroxidation peaked at day 6, suggesting a temporal relationship with DCI 115.…”

“…Generation of free radicals is related to auto-oxidation of haemoglobin in the CSF, altered mitochondrial function, lipid peroxidation, as well as NADPH oxidase function 123. Studies showed that generation of free radicals is important in the pathogenesis of CVS as well as DCI 115 116 119 120 122. Human data indicates an increase in oxidative stress and lipid peroxidation in serum as well as CSF within 3 days after SAH 115 118 119 120.…”

“…Studies showed that generation of free radicals is important in the pathogenesis of CVS as well as DCI 115 116 119 120 122. Human data indicates an increase in oxidative stress and lipid peroxidation in serum as well as CSF within 3 days after SAH 115 118 119 120. Furthermore, the increases are more pronounced in patients who developed DCI115 116 and those with poor neurological outcome 119 120.…”

“…Furthermore, the increases are more pronounced in patients who developed DCI115 116 and those with poor neurological outcome 119 120. Markers of CSF lipid peroxidation peaked at day 6, suggesting a temporal relationship with DCI 115. However, due to the lack of simultaneous clinical correlation it is difficult to judge whether they precipitated of were a consequence of ischaemia.…”