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ID 110032
Title Alternative
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
Author
Kung, David K. University of Pennsylvania
Kitazato, Keiko T. Tokushima University
Korai, Masaaki Tokushima University
Kurashiki, Yoshitaka Tokushima University
Kinouchi, Tomoya Tokushima University
Hashimoto, Tomoki University of California
Keywords
Animal Models
Cerebral Hemodynamics
Inflammation
Intracranial Aneurysm
Subarachnoid Hemorrhage
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Journal of Cerebral Blood Flow & Metabolism
ISSN
15597016
0271678X
NCID
AA12510484
AA10458430
Publisher
International Society for Cerebral Blood Flow and Metabolism|Sage
Volume
37
Issue
8
Start Page
2795
End Page
2805
Published Date
2016-01-01
Remark
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3005号
Diploma Number
甲医第1309号
Granted Date
2017-03-23
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences