Haptoglobin 2-2 genotype determines chronic vasospasm after experimental subarachnoid hemorrhage

Kaisorn L. Chaichana, Andrew P. Levy, Rachel Miller-Lotan, Sophia Shakur, Rafael J. Tamargo

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND AND PURPOSE - Chronic cerebral arterial vasospasm is the leading cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). Not all cases of SAH, however, develop chronic vasospasm. Inflammation, specifically leukocyte-endothelial cell interactions, appears to be critical in vasospasm development. Haptoglobin (Hp) is a serum protein that limits the extent of inflammation after a hemorrhagic event. An individual's Hp genotype may predict the severity of the inflammatory response during a hemorrhagic event, and consequently modulate the risk for vasospasm. METHODS - Sixty mice (Hp 1-1, n=30; Hp 2-2, n=30) underwent injection of either autologous blood or normal saline solution into the cisterna magna. An additional 30 mice (15 per genotype) served as controls. The extent and manifestations of vasospasm were assessed by measuring lumen patency, quantifying activity levels, and counting the number of vessel-infiltrated macrophages/neutrophils at 24 hours after injection, which corresponds to the time of peak vasospasm in mice. RESULTS - Genetically modified Hp 2-2 mice with SAH had significantly lower basilar artery lumen patencies (mean±SEM; 52.9±1.9% vs 82.3±1.3%; P<0.01), reduced activity levels (0.8±0.3 vs 2.4±0.2; P<0.01), and increased macrophage/neutrophil counts in the subarachnoid space (31.2±6.3 vs 8.8±1.7, P<0.01) as compared with wild-type Hp 1-1 mice. CONCLUSIONS - These findings suggest that the Hp 2-2 genotype is critical for the development of severe vasospasm, which typically occurs 24 hours after SAH in mice.

Original languageEnglish (US)
Pages (from-to)3266-3271
Number of pages6
JournalStroke
Volume38
Issue number12
DOIs
StatePublished - Dec 2007

Keywords

  • Haptoglobin
  • Subarachnoid hemorrhage
  • Vasospasm

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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