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Role of Bilirubin Oxidation Products in the Pathophysiology of DIND Following SAH

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Cerebral Vasospasm: Neurovascular Events After Subarachnoid Hemorrhage

Part of the book series: Acta Neurochirurgica Supplement ((NEUROCHIRURGICA,volume 115))

Abstract

Despite intensive research efforts, by our own team and many others, the molecules responsible for acute neurological damage following subarachnoid hemorrhage (SAH) and contributing to delayed ischemic neurological deficit (DIND) have not yet been elucidated. While there are a number of candidate mechanisms, including nitric oxide (NO) scavenging, endothelin-1, protein kinase C (PKC) activation, and rho kinase activation, to name but a few, that have been investigated using animal models and human trials, we are, it seems, no closer to discovering the true nature of this complex and enigmatic pathology. Efforts in our laboratory have focused on the chemical milieu present in hemorrhagic cerebrospinal fluid (CSF) following SAH and the interaction of the environment with the molecules generated by SAH and subsequent events, including NO scavenging, immune response, and clot breakdown. We have identified and characterized a group of molecules formed by the oxidative degradation of bilirubin (a clot breakdown product) and known as BOXes (bilirubin oxidation products). We present a synopsis of the characterization of BOXes as found in human SAH patients’ CSF and the multiple signaling pathways by which BOXes act. In summary, BOXes are likely to play an essential role in the etiology of acute brain injury following SAH, as well as DIND.

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Conflicts of Interest Statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Mayfield Neurovascular Research, Mayfield Clinic, Cincinnati, OH, USA

    Gail J. Pyne-Geithman D.Phil

  2. Department of Neurosurgery, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA

    Gail J. Pyne-Geithman D.Phil & Danielle N. Caudell Stamper BSN, RN

  3. Department of Systems Biology and Physiology, University of Cincinnati, Cincinnati, OH, USA

    Sunil G. Nair MBBS

  4. Department of Neurology, University of Cincinnati, Cincinnati, OH, USA

    Sunil G. Nair MBBS & Joseph F. Clark Ph.D.

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  1. Gail J. Pyne-Geithman D.Phil
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  2. Sunil G. Nair MBBS
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  3. Danielle N. Caudell Stamper BSN, RN
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  4. Joseph F. Clark Ph.D.
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Correspondence to Gail J. Pyne-Geithman D.Phil .

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Editors and Affiliations

  1. , Department of Neurosurgery, University of Cincinnati, Stetson, Suite 2200 260, Cincinnati, 45267-0515, Ohio, USA

    Mario Zuccarello

  2. College of Medicine, Department of Neurology, University of Cincinnati, Albert Sabin Way 231MSB room 1, Cincinnati, 46267-0536, Ohio, USA

    Joseph F. Clark

  3. College of Medicine, Dept. of Neurology and Neurosurgery, University of Cincinnati, Albert Sabin Way 231ML0517, Cincinnati, 45267-0517, Ohio, USA

    Gail Pyne-Geithman

  4. College of Medicine, Dept. of Neurosurgery, University of Cincinnati, Stetson St. Suite 260ML0515, Cincinnati, 45219, Ohio, USA

    Norberto Andaluz

  5. College of Medicine, Dept. of Neurosurgery, University of Cincinnati, Stetson, Suite 2200 260, Cincinnati, 45219, Ohio, USA

    Jed A. Hartings

  6. , Dept. of Emergency Medicine, University of Cincinnati, Albert Sabin Way 231ML0769, Cincinnati, 45267-0769, Ohio, USA

    Opeolu M. Adeoye

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Pyne-Geithman, G.J., Nair, S.G., Stamper, D.N.C., Clark, J.F. (2013). Role of Bilirubin Oxidation Products in the Pathophysiology of DIND Following SAH. In: Zuccarello, M., Clark, J., Pyne-Geithman, G., Andaluz, N., Hartings, J., Adeoye, O. (eds) Cerebral Vasospasm: Neurovascular Events After Subarachnoid Hemorrhage. Acta Neurochirurgica Supplement, vol 115. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1192-5_47

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