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Role of Bilirubin Oxidation Products in delayed Cerebral Vasospasm after Subarachnoid Hemorrhage‐ an in vitro study
Author(s) -
Nair Sunil G,
Clark Joseph F,
Wurster William L,
PyneGeithman Gail J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1148.11
Subject(s) - subarachnoid hemorrhage , cerebral vasospasm , vasospasm , in vivo , medicine , long term potentiation , cerebrospinal fluid , contraction (grammar) , pathophysiology , bilirubin , in vitro , chemistry , anesthesia , pharmacology , endocrinology , biology , biochemistry , receptor , microbiology and biotechnology
Delayed Cerebral Vasospasm (CV) is a crucial and often fatal complication of Subarachnoid hemorrhage (SAH). The etiology and molecular mechanism of CV is still a mystery. Recent reports have shown that Bilirubin Oxidation Products (BOXes) are present in significantly greater concentrations in the cerebrospinal fluid of patients with SAH who suffer from vasospasm (CSF V ) than in those who do not (CSF C ). Previous studies have shown that BOXes are vasoactive in vivo and potentiate smooth muscle contraction similar to PKC activators and phosphatase inhibitors in vitro. Using tissue bath apparatus, we examined the potentiation of phenylephrine (PE)‐induced force‐generation by various concentrations of BOXes in porcine carotid artery tissue rings. 1.5 – 7 μmol/L BOXes showed significantly increased potentiation of PE‐induced contraction when compared to vehicle. This was also observed with CSF V . We also studied the cytoplasm‐to‐membrane translocation of PKC's α and δ, and Rho in the presence of three different patho‐physiologically relevant concentrations of BOXes (0.2, 2 & 20μmol/L) at two‐points (20 minutes and 3 hours). Translocation of these proteins indicates their activation. Both PKC's and Rho were translocated in a time‐ and dose‐dependent manner by BOXes. Therefore, we postulate that BOXes may be one of the major molecules responsible for the etiology of CV after SAH.