Pharmacological stabilization of intracranial aneurysms in mice— a feasibility study
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 approa...
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Main Authors: | , , , , , , , , , , , |
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Formato: | Artigo |
Idioma: | Inglês |
Publicado em: |
2012
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Assuntos: | |
Acesso em linha: | https://ncbi.nlm.nih.gov/pmc/articles/PMC3429647/ https://ncbi.nlm.nih.gov/pubmed/22798328 https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1161/STROKEAHA.112.659821 |
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Resumo: | 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 six days after aneurysm induction. Aneurysmal rupture was detected by neurological symptoms and confirmed by the presence of intracranial aneurysm with subarachnoid hemorrhage. RESULTS: Minocycline and doxycycline significantly reduced rupture rates (vehicle vs. doxycycline = 80 vs. 35%, P < 0.05; vehicle vs. minocycline = 73 vs. 24%, P < 0.05) without affecting the overall incidence of aneurysms. However, SB-3CT did not affect the rupture rate (62 vs. 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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