Document Detail

Pharmacological stabilization of intracranial aneurysms in mice: a feasibility study.
MedLine Citation:
PMID:  22798328     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-12
Journal Detail:
Title:  Stroke; a journal of cerebral circulation     Volume:  43     ISSN:  1524-4628     ISO Abbreviation:  Stroke     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-28     Completed Date:  2012-11-05     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  0235266     Medline TA:  Stroke     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2450-6     Citation Subset:  IM    
Department of Anesthesia and Perioperative Care, University of California, San Francisco, 1001 Potrero Avenue, No. 3C-38, San Francisco, CA 94110, USA.
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MeSH Terms
Aneurysm, Ruptured / drug therapy,  pathology
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
Matrix Metalloproteinase Inhibitors
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
Reg. No./Substance:
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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