2010 Fiscal Year Final Research Report
molecular mechanisms in the formation and rupture of cerebral aneurysm and impact of drug treatment
| Project/Area Number |
21390412
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | The University of Tokushima |
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Principal Investigator |
NAGAHIRO Shinji The University of Tokushima, 大学院・ヘルスバイオサイエンス研究部, 教授 (60145315)
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| Co-Investigator(Kenkyū-buntansha) |
SATA Masataka 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (80345214)
SATOMI Junichiro 徳島大学, 病院, 講師 (10304510)
KANEMATSU Yasuhisa 徳島大学, 病院, 助教 (90363142)
YAGI Kenji 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (80551837)
TADA Yoshiteru 徳島大学, 病院, 助教 (30547964)
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| Project Period (FY) |
2009 – 2010
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| Keywords | 脳動脈瘤 / タイトジャンクション蛋白 / mineral corticoid receptor / phosphodiesterase / 血管内皮障害 / angiotensin II / エストロゲン / 炎症 |
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| Research Abstract |
The pathogensis of cerebral aneursysm is multifactorial. To elucidate on how to generate, grow, and rupture, we establish a reproducible aneurysmal model in estrogen deficient female rats. Using this model, we first demonstrated that the reduction of tight junction protein induced by oxidative stress and inflammatory led to the degradation of endothelial gap, thereby facilitating the infiltration of macrophages into the aneurysmal wall. The increase in macrophage promotes inflammation, directed to vice cycle, resulting in the growth and rupture of cerebral aneurysm. To assess whether some drugs are possible to inhibit the formation and growth of cerebral aneurysms, we used an angiotensin typeI receptor a blockade,phosphodiesterase 4 inhibitor, 17・estradiol in hormonal replacement therapy and a mineralcorticoid receptor antagonist.These drugs were effective to prevent the formation of cerebral aneurysms and the mechanism underlying the effects by these drugs associated with anti-oxidative and anti-inflammatory. On the other hand, statins exerted diverse effects; beneficial and deleterious effects. Notably, a high dose satin and a lipophilic statin induced rupture. Furthermore, we found new evidence that the combination of estrogen deficiency and high salt intake is exclusively associated with the formation of cerebral aneurysm. In the further study, we will verify the relationship between high salt intake and cerebral aneurysms.
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