Heme oxygenase-1 and ferritin are increased in cerebral arteries after subarachnoid hemorrhage in monkeys

Hemoglobin is a key factor in the production of cerebral vasospasm. Metabol ism of hemoglobin involves breakdown of heme by heme oxygenase (HO) and seq uestration of the released iron in ferritin. We determined whether subarach noid hemorrhage induces these proteins in cerebral arteries and, if so, in which cells they are produced. Whether the changes correlated with vasospas m also was investigated. Subarachnoid hemorrhage was created in monkeys, an d vasospasm was assessed by angiography in cohorts of animals killed 3, 7, or 14 days after the hemorrhage. Ferritin and HO-1 messenger ribonucleic ac id (mRNA) and protein were measured by competitive reverse transcription-po lymerase chain reaction and Western blotting in hemorrhage-side and control -side cerebral arteries and brain tissue. The location of these proteins wa s determined by immunohistochemistry. There was significant vasospasm 3 and 7 days but not 14 days after subarachnoid hemorrhage. There were no signif icant changes in mRNA for HO-1 or ferritin in cerebral arteries or brain ti ssue at any time. There was a significant increase in HO-1 and ferritin pro tein in hemorrhage-side compared with control-side cerebral arteries at 3, 7, and 14 days. The increase in HO-1 protein was maximal at 3 days, whereas the increase in ferritin protein was maximal at 7 days. There was no detec table increase in HO-1 or ferritin protein in brain tissue at any time. Imm unohistochemistry localized HO-1 protein and ferritin to cells in the adven titia of the arterial wall. We show that subarachnoid hemorrhage is associa ted with a significant increase in HO-1 and ferritin proteins in cerebral a rteries that begins at least as early as 3 days after the hemorrhage and th at persists for up to 14 days.