| Pharmacological stabilization of intracranial aneurysms in mice: a feasibility study. | |
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MedLine Citation:
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PMID: 22798328 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: An increasing number of unruptured intracranial aneurysms are being detected, partly due to the increased use of brain imaging techniques. Pharmacological stabilization of aneurysms for the prevention of aneurysmal rupture could potentially be an attractive alternative approach to clipping or coiling in patients with unruptured intracranial aneurysms. We have developed a mouse model of intracranial aneurysm that recapitulates key features of intracranial aneurysms. In this model, subarachnoid hemorrhage from aneurysmal rupture causes neurological symptoms that can be easily detected by a simple neurological examination. Using this model, we tested whether anti-inflammatory agents such as tetracycline derivatives, or a selective inhibitor of matrix metalloproteinases-2 and -9 (SB-3CT), can prevent the rupture of intracranial aneurysms. METHODS: Aneurysms were induced by a combination of induced hypertension and a single injection of elastase into the cerebrospinal fluid in mice. Treatment with minocycline, doxycycline, or SB-3CT was started 6 days after aneurysm induction. Aneurysmal rupture was detected by neurological symptoms and confirmed by the presence of intracranial aneurysms with subarachnoid hemorrhage. RESULTS: Minocycline and doxycycline significantly reduced rupture rates (vehicle versus doxycycline=80% versus 35%, P<0.05; vehicle versus minocycline=73% versus 24%, P<0.05) without affecting the overall incidence of aneurysms. However, SB-3CT did not affect the rupture rate (62% versus 55%, P=0.53). CONCLUSIONS: Our data established the feasibility of using a mouse model of intracranial aneurysm to test pharmacological stabilization of aneurysms. Tetracycline derivatives could be potentially effective in preventing aneurysmal rupture. |
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Authors:
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Hiroshi Makino; Yoshiteru Tada; Kosuke Wada; Elena I Liang; Mayland Chang; Shahriar Mobashery; Yasuhisa Kanematsu; Chie Kurihara; Emma Palova; Miyuki Kanematsu; Keiko Kitazato; Tomoki Hashimoto |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-07-12 |
Journal Detail:
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Title: Stroke; a journal of cerebral circulation Volume: 43 ISSN: 1524-4628 ISO Abbreviation: Stroke Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-08-28 Completed Date: 2012-11-05 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0235266 Medline TA: Stroke Country: United States |
Other Details:
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Languages: eng Pagination: 2450-6 Citation Subset: IM |
Affiliation:
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Department of Anesthesia and Perioperative Care, University of California, San Francisco, 1001 Potrero Avenue, No. 3C-38, San Francisco, CA 94110, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aneurysm, Ruptured
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drug therapy,
pathology Animals Blood Pressure / drug effects Disease Models, Animal Doxycycline / therapeutic use Feasibility Studies Gelatinases / metabolism Heterocyclic Compounds, 1-Ring / therapeutic use Intracranial Aneurysm / drug therapy*, pathology Male Matrix Metalloproteinase Inhibitors Mice Mice, Inbred C57BL Minocycline / therapeutic use Neurologic Examination Protease Inhibitors / therapeutic use Subarachnoid Hemorrhage / drug therapy, pathology Sulfones / therapeutic use Survival Analysis Tetracyclines / therapeutic use |
| Grant Support | |
ID/Acronym/Agency:
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P01 NS044155/NS/NINDS NIH HHS; R01 NS055876/NS/NINDS NIH HHS; R01CA122417/CA/NCI NIH HHS; R01NS055876/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Heterocyclic Compounds, 1-Ring; 0/Matrix Metalloproteinase Inhibitors; 0/Protease Inhibitors; 0/SB 3CT compound; 0/Sulfones; 0/Tetracyclines; 10118-90-8/Minocycline; 564-25-0/Doxycycline; EC 3.4.24.-/Gelatinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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