Document Detail


Cerebral aneurysm formation in nitric oxide synthase-3 knockout mice.
MedLine Citation:
PMID:  17691969     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We sought to evaluate the influence of specific vasoactive gene knockouts on the process of intracranial aneurysm formation in mice. Thirty wild type, 7 nitric oxide synthase (NOS)-2 knockout, 6 NOS-3 knockout, and 8 plasminogen activator inhibitor (PAI)-1 knockout female mice underwent left common carotid artery ligation at 2 to 6 months of age. After a survival period (average 20.4 months +/- 1.5 months), the brains were perfusion fixed with 10% buffered formalin for 10 minutes and then perfused with India ink. Brain and intact cerebral circulation were surgically removed and further fixed in 10% buffered formalin for 4 additional days. The basal cerebral circulation of each brain was examined for the presence of intracranial aneurysms under a surgical microscope (3x-21x). Suspected aneurysms were further dissected for histological analysis. Specimens were embedded in epoxy resin, cut into 0.5 and 1.0 micron sections, and stained with Toluidine blue. A neuropathologist blinded to genotype and surgical microscopy results examined the slides for evidence of aneurysmal pathology. Two intracranial aneurysms in 2 NOS-3 knockout mice were confirmed by histology. No intracranial aneurysms were confirmed in any wild type, NOS-2 knockout, or PAI-1 knockout mice. Histological analysis of aneurysms revealed loss of elastica, subendothelial collagen deposition, and perivascular lymphocytic infiltration. Our results suggest that NOS-3 knockout, but not PAI-1 or NOS-2 knockout, predisposes to the formation of intracranial aneurysms in mice subjected to unilateral carotid artery ligation. Due to small sample sizes however, selection bias cannot be excluded and further investigation is necessary to confirm our results.
Authors:
Todd Abruzzo; Ady Kendler; Robert Apkarian; Michael Workman; Jane C Khoury; Harry J Cloft
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Current neurovascular research     Volume:  4     ISSN:  1567-2026     ISO Abbreviation:  -     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-08-13     Completed Date:  2007-10-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  101208439     Medline TA:  Curr Neurovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  161-9     Citation Subset:  IM    
Affiliation:
The Neuroscience Institute: Section of Interventional and Endovascular Surgical Neuroradiology, Department of Neurosurgery, University of Cincinnati Colleges of Medicine and Engineering, Cincinnati, Ohio, USA. abruzzta@healthall.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Female
Intracranial Aneurysm / genetics*,  pathology*
Mice
Mice, Knockout
Nitric Oxide Synthase Type II / deficiency*
Nitric Oxide Synthase Type III
Plasminogen Activator Inhibitor 1 / deficiency
Chemical
Reg. No./Substance:
0/Plasminogen Activator Inhibitor 1; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, mouse

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