Haptoglobin 2-2 genotype determines chronic vasospasm after experimental subarachnoid hemorrhage.
OBJECTIVE
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.
Chaichana
Kaisorn L
KL
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Levy
Andrew P
AP
Miller-Lotan
Rachel
R
Shakur
Sophia
S
Tamargo
Rafael J
RJ
D000483:Alleles; D000818:Animals; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006242:Haptoglobins / Q000235:genetics*; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000175:diagnosis* / Q000235:genetics*; D013997:Time Factors; D020301:Vasospasm, Intracranial / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics*
D006242:Haptoglobins