title: Vasospasm after subarachnoid hemorrhage in haptoglobin 2-2 mice can be prevented with a glutathione peroxidase mimetic.
abstract: Vasospasm after subarachnoid hemorrhage (SAH) is attributable to inflammation and oxidative stress associated with extracellular hemoglobin (Hb). Haptoglobin (Hp) binds free Hb and the Hp-Hb complex is cleared by macrophages, and the Hp-2 isoform of Hp is associated with more oxidative stress and more severe vasospasm. We hypothesized that treatment with an anti-oxidant, the glutathione peroxidase mimetic SYI-2074, would reduce vasospasm after SAH in Hp-2 mice. We found that SAH induced significant vasospasm in Hp-2 mice (lumen patency reduced to 65.9%), but no vasospasm was seen in mice that received SYI-2074 after SAH (lumen patency of 98.7%). We conclude that vasospasm after SAH in Hp-2 mice can be prevented with SYI-2074, suggesting that oxidative stress contributes significantly to vasospasm.
authors.affiliation: Interventional Neuroradiology, University of California Los Angeles, 757 Westwood Plaza, Ste 2129, Los Angeles, CA 90095, USA. mfroehler@mednet.ucla.edu
authors.forename: Michael T
authors.initials: MT
authors.lastname: Froehler
authors.forename: Ali
authors.initials: A
authors.lastname: Kooshkabadi
authors.forename: Rachel
authors.initials: R
authors.lastname: Miller-Lotan
authors.forename: Shany
authors.initials: S
authors.lastname: Blum
authors.forename: Slava
authors.initials: S
authors.lastname: Sher
authors.forename: Andrew
authors.initials: A
authors.lastname: Levy
authors.forename: Rafael J
authors.initials: RJ
authors.lastname: Tamargo
mesh_terms: D000818:Animals; D005979:Glutathione Peroxidase / Q000494:pharmacology / Q000627:therapeutic use*; D006242:Haptoglobins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D018716:Molecular Mimicry; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*
chemical_list: D006242:Haptoglobins; D005979:Glutathione Peroxidase