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A Murine Model of Carotid Aneurysm Formation
Published on: September 9, 2025
Cerebral aneurysm formation in nitric oxide synthase-3 knockout mice
Todd Abruzzo1, Ady Kendler, Robert Apkarian
1The 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
Current Neurovascular Research
|August 19, 2007
Summary
Nitric oxide synthase-3 (NOS-3) knockout mice showed increased intracranial aneurysm formation after carotid artery ligation. Other gene knockouts, including nitric oxide synthase-2 (NOS-2) and plasminogen activator inhibitor-1 (PAI-1), did not show this predisposition.
Area of Science:
- Vascular Biology
- Genetics
- Neurology
Background:
- Intracranial aneurysms (IAs) are a significant cause of cerebrovascular disease.
- The genetic and molecular mechanisms underlying IA formation are not fully understood.
- Vasoactive pathways, particularly those involving nitric oxide, are implicated in vascular health.
Purpose of the Study:
- To investigate the role of specific vasoactive gene knockouts in the development of intracranial aneurysms.
- To determine if nitric oxide synthase (NOS)-2, NOS-3, or plasminogen activator inhibitor (PAI)-1 gene deficiencies influence IA formation in a mouse model.
Main Methods:
- Female mice with knockout genes for NOS-2, NOS-3, or PAI-1, along with wild-type controls, underwent left common carotid artery ligation.
- Brains were harvested after an average survival of 20.4 months, perfused with India ink, and examined for IAs.
- Histological analysis of suspected aneurysms was performed by a blinded neuropathologist.
Main Results:
- Two intracranial aneurysms were confirmed in NOS-3 knockout mice.
- No intracranial aneurysms were found in wild-type, NOS-2 knockout, or PAI-1 knockout mice.
- Histology of confirmed aneurysms revealed elastica loss, collagen deposition, and lymphocytic infiltration.
Conclusions:
- NOS-3 knockout, but not NOS-2 or PAI-1 knockout, appears to predispose mice to intracranial aneurysm formation following carotid artery ligation.
- Further research is needed to confirm these findings due to small sample sizes and potential selection bias.
