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新規脳動脈瘤ラットモデルにおける血行力学的変化によるウィリス動脈輪内の部位特異的なIL-1βとMMP-9の上昇は破裂に関連する
Rupture related to site-specific MMP-9 elevation
著者
宮本, 健志 徳島大学大学院医科学教育部(医学専攻)
Kung, David K. University of Pennsylvania
Kitazato, Keiko T. Tokushima University
倉敷, 佳孝 Tokushima University
木内, 智也 Tokushima University
Hashimoto, Tomoki University of California
キーワード
Animal Models
Cerebral Hemodynamics
Inflammation
Intracranial Aneurysm
Subarachnoid Hemorrhage
資料タイプ
学位論文
抄録
The pathogenesis of subarachnoid hemorrhage (SAH)remains unclear. No models of cerebral aneurysms elicited solely by surgical procedures and diet have been established.Elsewhere we reported that only few rats in our original rat aneurysm model manifested rupture at the anterior-and posterior Willis circle (AW, PW) and thatmany harbored unruptured aneurysms at the anterior cerebral artery-olfactory artery bifurcation (ACA-OA). This suggests that rupture was site-specific. To test our hypothesis that a site-specific responseto hemodynamic changes is associated with aneurysmal rupture, we modified our original aneurysm model by altering the hemodynamics. During 90-day observation, the incidenceof ruptured aneurysms at the AW and PWwas significantly increasedand the high incidence of unruptured aneurysms at the ACA-OA persisted. This phenomenon was associatedwith an increase in the blood flow volume (BFVo). Notably, the level of matrix metalloproteinase(MMP)-9 associated with interleukin (IL)-1βwas augmented by the increase in the BFVo, suggesting that these molecules exacerbated the vulnerability of the aneurysmal wall. The current study first demonstrates that a site-specificincrease in IL-1β and MMP-9 elicited by hemodynamic changes is associated with rupture. Our novel rat model of rupture may help to developpharmaceutical approaches to prevent rupture.
掲載誌名
Journal of Cerebral Blood Flow & Metabolism
ISSN
15597016
0271678X
cat書誌ID
AA12510484
AA10458430
出版者
International Society for Cerebral Blood Flow and Metabolism|Sage
37
8
開始ページ
2795
終了ページ
2805
発行日
2016-01-01
備考
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨:LID201704111003.pdf
論文本文:LID201704111004.pdf
本論文は, 著者Takeshi Miyamotoの学位論文として提出され, 学位審査・授与の対象となっている。
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3005号
学位記番号
甲医第1309号
学位授与年月日
2017-03-23
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
医学系