Vasospasm after subarachnoid hemorrhage in haptoglobin 2-2 mice can be prevented with a glutathione peroxidase mimetic

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 SAN in Hp-2 mice. We found that SAN 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 SAN in Hp-2 mice can be prevented with SYI-2074, suggesting that oxidative stress contributes significantly to vasospasm. (C) 2010 Elsevier Ltd. All rights reserved.