1. ¹Department of Neurology, University of Cincinnati, Cincinnati, Ohio, USA
2. ²Department of Neurosurgery, University of Cincinnati, Cincinnati, Ohio, USA
3. ³Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA
4. ⁴The Neuroscience Institute, Medical Research Service, Cincinnati, Ohio, USA
5. ⁵Mayfield Clinic, Cincinnati, Ohio, USA

Correspondence: Dr GJ Pyne-Geithman, Department of Neurology, University of Cincinnati, 3125 Eden Avenue, 2324 Vontz Center for Molecular Studies, Cincinnati, OH 45267-0536, USA. E-mail: pynegj@email.uc.edu

Received 23 November 2004; Revised 6 January 2005; Accepted 24 January 2005; Published online 23 March 2005.

Abstract

Delayed cerebral vasospasm after subarachnoid hemorrhage (SAH) remains a significant cause of mortality and morbidity; however, the etiology is, as yet, unknown, despite intensive research efforts. Research in this laboratory indicates that bilirubin and oxidative stress may be responsible by leading to formation of bilirubin oxidation products (BOXes), so we investigated changes in bilirubin concentration and oxidative stress in vitro, and in cerebral spinal fluid (CSF) from SAH patients. Non-SAH CSF, a source of heme oxygenase I (HO-1), and blood were incubated, and in vitro bilirubin production measured. Cerebrospinal fluid from SAH patients was collected, categorized using stimulation of vascular smooth muscle metabolism in vitro, and information obtained regarding occurrence of vasospasm in the patients. Cerebral spinal fluid was analyzed for hemoglobin, total protein and bilirubin, BOXes, malonyldialdehyde and peroxidized lipids (indicators of an oxidizing environment), and HO-1 concentration. The formation of bilirubin in vitro requires that CSF is present, as well as whole, non-anti-coagulated blood. Bilirubin, BOXes, HO-1, and peroxidized lipid content were significantly higher in CSF from SAH patients with vasospasm, compared with nonvasospasm SAH CSF, and correlated with occurrence of vasospasm. We conclude that vasospasm may be more likely in patients with elevated BOXes. The conditions necessary for the formation of BOXes are indeed present in CSF from SAH patients with vasospasm, but not CSF from SAH patients without vasospasm.