Site-specific elevation of interleukin-1β and matrix metalloproteinase-9 in the Willis circle by hemodynamic changes is associated with rupture in a novel rat cerebral aneurysm model

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.

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。