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: Michael T Froehler, Ali Kooshkabadi, Rachel Miller-Lotan, Shany Blum, Slava Sher, Andrew Levy, Rafael J Tamargo
• Journal: Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia (J Clin Neurosci) Vol. 17 Issue 9 Pg. 1169-72 (Sep 2010) ISSN: 1532-2653 [Electronic] Scotland
• PMID: 20541941 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Haptoglobins
• Glutathione Peroxidase

Topics

• Animals
• Glutathione Peroxidase (pharmacology, therapeutic use)
• Haptoglobins (genetics)
• Mice
• Mice, Transgenic
• Molecular Mimicry
• Subarachnoid Hemorrhage (complications, drug therapy, genetics)
• Vasoconstriction (drug effects, physiology)
• Vasospasm, Intracranial (etiology, genetics, prevention & control)