Oxidation of bilirubin produces compounds that cause prolonged vasospasm of rat cerebral vessels: A contributor to subarachnoid hemorrhage-induced vasospasm

Joseph F. Clark, Melinda Reilly, Frank R Sharp

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Summary: The authors have previously shown that bilirubin-oxidation products (BOXes) are present in CSF of subarachnoid hemorrhage patients with vasospasm, and that BOXes cause vasoconstriction in vitro. This study determined whether BOXes cause vasospasm in vivo. Identical volumes of either lysed blood or standardized amounts of BOXes were injected into the cisterna magna of adult rats. BOX injections caused 6 of 10 rats to die within 10 minutes, whereas 12 of 12 rats survived for 24 hours after blood injections. The mechanism for this significant (P ≤ 0.01) increase in mortality was unclear. To directly test whether BOXes produced vasospasm, a cranial window technique was used. Application of 20 μL of 10 μmol/L bilirubin had little effect on the vessels. However, application of BOXes produced marked, dose-dependent small artery and arteriole vasospasm that approached a 90% decrease in diameter by 40 minutes after application in some vessels, and persisted for at least 24 hours. To determine if BOX-mediated vasospasm led to cortical injury, histology and immunocytochemistry were performed on animals that survived for 24 hours. There was a BOX-related stress protein response for HSP25 and HSP32 (HO-1) without evidence of infarction. The finding that the BOXes produce vasospasm of cerebral vessels in vivo, in conjunction with BOXes being found in CSF of vasospasm patients, supports our hypothesis that BOXes contribute to or cause cerebral vasospasm after subarachnoid hemorrhage.

Original languageEnglish (US)
Pages (from-to)472-478
Number of pages7
JournalJournal of Cerebral Blood Flow and Metabolism
Volume22
Issue number4
StatePublished - 2002
Externally publishedYes

Keywords

  • Bilirubin
  • Cerebral vasospasm
  • Hemorrhage
  • Oxidative stress
  • Relaxation
  • Vessel diameter

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

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