title: 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.
abstract: The pathogenesis of subarachnoid hemorrhage 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 and that many harbored unruptured aneurysms at the anterior cerebral artery-olfactory artery bifurcation. This suggests that rupture was site-specific. To test our hypothesis that a site-specific response to hemodynamic changes is associated with aneurysmal rupture, we modified our original aneurysm model by altering the hemodynamics. During 90-day observation, the incidence of ruptured aneurysms at the anterior and posterior Willis circle was significantly increased and the high incidence of unruptured aneurysms at the anterior cerebral artery-olfactory artery persisted. This phenomenon was associated with an increase in the blood flow volume. Notably, the level of matrix metalloproteinase-9 associated with interleukin-1β was augmented by the increase in the blood flow volume, suggesting that these molecules exacerbated the vulnerability of the aneurysmal wall. The current study first demonstrates that a site-specific increase in interleukin-1β and matrix metalloproteinase-9 elicited by hemodynamic changes is associated with rupture. Our novel rat model of rupture may help to develop pharmaceutical approaches to prevent rupture.
authors: 1 Department of Neurosurgery, Tokushima University Graduate School, Tokushima, Japan.
authors: Takeshi
authors: T
authors: Miyamoto
authors: 2 Department of Neurosurgery, University of Pennsylvania, Philadelphia, USA.
authors: David K
authors: DK
authors: Kung
authors: 1 Department of Neurosurgery, Tokushima University Graduate School, Tokushima, Japan.
authors: Keiko T
authors: KT
authors: Kitazato
authors: 1 Department of Neurosurgery, Tokushima University Graduate School, Tokushima, Japan.
authors: Kenji
authors: K
authors: Yagi
authors: 1 Department of Neurosurgery, Tokushima University Graduate School, Tokushima, Japan.
authors: Kenji
authors: K
authors: Shimada
authors: 1 Department of Neurosurgery, Tokushima University Graduate School, Tokushima, Japan.
authors: Yoshiteru
authors: Y
authors: Tada
authors: 1 Department of Neurosurgery, Tokushima University Graduate School, Tokushima, Japan.
authors: Masaaki
authors: M
authors: Korai
authors: 1 Department of Neurosurgery, Tokushima University Graduate School, Tokushima, Japan.
authors: Yoshitaka
authors: Y
authors: Kurashiki
authors: 1 Department of Neurosurgery, Tokushima University Graduate School, Tokushima, Japan.
authors: Tomoya
authors: T
authors: Kinouchi
authors: 1 Department of Neurosurgery, Tokushima University Graduate School, Tokushima, Japan.
authors: Yasuhisa
authors: Y
authors: Kanematsu
authors: 1 Department of Neurosurgery, Tokushima University Graduate School, Tokushima, Japan.
authors: Junichiro
authors: J
authors: Satomi
authors: 3 Department of Anesthesia and Perioperative Care, University of California, San Francisco, USA.
authors: Tomoki
authors: T
authors: Hashimoto
authors: 1 Department of Neurosurgery, Tokushima University Graduate School, Tokushima, Japan.
authors: Shinji
authors: S
authors: Nagahiro
mesh_terms: D017542:Aneurysm, Ruptured / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D002560:Cerebrovascular Circulation / Q000502:physiology; D002941:Circle of Willis / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D006439:Hemodynamics / Q000502:physiology*; D053583:Interleukin-1beta / Q000378:metabolism*; D002532:Intracranial Aneurysm / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D053583:Interleukin-1beta; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: Animal models; cerebral hemodynamics; inflammation; intracranial aneurysm; subarachnoid hemorrhage