Abstract WP76: Shear Stress Sensing on the Endothelium Initiates Chronic Inflammation of the Arterial Wall During Cerebral Aneurysm Formation: Potential Novel Therapy for Cerebral Aneurysms With Paroxetine

Stroke ◽  
2018 ◽  
Vol 49 (Suppl_1) ◽  
Author(s):  
Shunichi Fukuda ◽  
Miyuki Fukuda ◽  
Joji Ando ◽  
Kimiko Yamamoto ◽  
Tetsuya Tsukahara ◽  
...  
Keyword(s):  
Shear Stress ◽  
Cerebral Aneurysm ◽  
Chronic Inflammation ◽  
Arterial Wall ◽  
Cerebral Aneurysms ◽  
Novel Therapy ◽  
Formation Potential ◽  
Aneurysm Formation ◽  
Stress Sensing

scholarly journals Disruption of P2X4 purinoceptor and suppression of the inflammation associated with cerebral aneurysm formation

2019 ◽  
pp. 1-13 ◽  
Author(s):  
Miyuki Fukuda ◽  
Shunichi Fukuda ◽  
Joji Ando ◽  
Kimiko Yamamoto ◽  
Naohiro Yonemoto ◽  
...  
Keyword(s):  
Shear Stress ◽  
Cerebral Aneurysm ◽  
Arterial Wall ◽  
Quantitative Polymerase Chain Reaction ◽  
Cerebral Aneurysms ◽  
Artery Ligation ◽  
Hemodynamic Stress ◽  
Aneurysm Formation ◽  
Aneurysm Development ◽  
Cox 2

OBJECTIVEThere are no effective therapeutic drugs for cerebral aneurysms, partly because the pathogenesis remains unresolved. Chronic inflammation of the cerebral arterial wall plays an important role in aneurysm formation, but it is not clear what triggers the inflammation. The authors have observed that vascular endothelial P2X4 purinoceptor is involved in flow-sensitive mechanisms that regulate vascular remodeling. They have thus hypothesized that shear stress–associated hemodynamic stress on the endothelium causes the inflammatory process in the cerebral aneurysm development.METHODSTo test their hypothesis, the authors examined the role of P2X4 in cerebral aneurysm development by using P2X4−/− mice and rats that were treated with a P2X4 inhibitor, paroxetine, and subjected to aneurysm-inducing surgery. Cerebral aneurysms were induced by unilateral carotid artery ligation and renovascular hypertension.RESULTSThe frequency of aneurysm induction evaluated by light microscopy was significantly lower in the P2X4−/− mice (p = 0.0488) and in the paroxetine-treated male (p = 0.0253) and female (p = 0.0204) rats compared to control mice and rats, respectively. In addition, application of paroxetine from 2 weeks after surgery led to a significant reduction in aneurysm size in the rats euthanized 3 weeks after aneurysm-inducing surgery (p = 0.0145), indicating that paroxetine suppressed enlargement of formed aneurysms. The mRNA and protein expression levels of known inflammatory contributors to aneurysm formation (monocyte chemoattractant protein–1 [MCP-1], interleukin-1β [IL-1β], tumor necrosis factor–α [TNFα], inducible nitric oxide synthase [iNOS], and cyclooxygenase-2 [COX-2]) were all significantly elevated in the rats that underwent the aneurysm-inducing surgery compared to the nonsurgical group, and the values in the surgical group were all significantly decreased by paroxetine administration according to quantitative polymerase chain reaction techniques and Western blotting. Although immunolabeling densities for COX-2, iNOS, and MCP-1 were not readily observed in the nonsurgical mouse groups, such densities were clearly seen in the arterial wall of P2X4+/+ mice after aneurysm-inducing surgery. In contrast, in the P2X4−/− mice after the surgery, immunolabeling of COX-2 and iNOS was not observed in the arterial wall, whereas that of MCP-1 was readily observed in the adventitia, but not the intima.CONCLUSIONSThese data suggest that P2X4 is required for the inflammation that contributes to both cerebral aneurysm formation and growth. Enhanced shear stress–associated hemodynamic stress on the vascular endothelium may trigger cerebral aneurysm development. Paroxetine may have potential for the clinical treatment of cerebral aneurysms, given that this agent exhibits efficacy as a clinical antidepressant.

scholarly journals Excessive shear stress sensing on the arterial endothelium initiates cerebral aneurysm formation

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Miyuki Fukuda ◽  
Shunichi Fukuda ◽  
Joji Ando ◽  
Kimiko Yamamoto ◽  
Yuki Ito ◽  
...  
Keyword(s):  
Shear Stress ◽  
Cerebral Aneurysm ◽  
Aneurysm Formation ◽  
Stress Sensing ◽  
Arterial Endothelium

Histologically verified cerebral aneurysm formation secondary to embolism from cardiac myxoma

1995 ◽  
Vol 83 (1) ◽  
pp. 170-173 ◽  
Author(s):  
Kazuhide Furuya ◽  
Tomio Sasaki ◽  
Yuhei Yoshimoto ◽  
Yoshifumi Okada ◽  
Takamitsu Fujimaki ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cardiac Tumor ◽  
Arterial Wall ◽  
Cardiac Myxoma ◽  
Cerebral Aneurysms ◽  
Surgical Removal ◽  
Arterial Aneurysm ◽  
Content Type ◽  
Aneurysm Formation ◽  
Aneurysm Wall

✓ Multiple aneurysm formation secondary to an embolism from the cardiac myxoma is a well-known phenomenon. The cerebral arterial aneurysm formation process involved remains to be elucidated, although occupation of the arterial wall by tumor cells has been proven histologically. The authors present the case of a patient in whom tumor cells in the aneurysm wall were demonstrated and penetration of viable myxoma cells into the wall was also observed 19 months after surgical removal of the cardiac tumor. Such findings have never before been verified histologically. In light of the histological findings, the authors discuss the therapeutic problems associated with cerebral aneurysms resulting from cardiac myxoma.

Abstract TP78: Down-regulation Of Vascular Na+/k+ ATPase In Oophorectomized Rats Feeding A High Salt Diet Is Associated With The Cerebral Aneurysm Formation

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Nobuhisa Matsushita ◽  
Yoshiteru Tada ◽  
Kenji Yagi ◽  
Keiko T Kitazato ◽  
Kenji Shimada ◽  
...  
Keyword(s):  
Cerebral Aneurysm ◽  
Efflux Pump ◽  
Cerebral Aneurysms ◽  
The Body ◽  
High Salt ◽  
Artery Ligation ◽  
High Salt Diet ◽  
Salt Diet ◽  
Aneurysm Formation ◽  
Water Ratio

Background and Purpose— Hypertension is thought to be associated with a high incidence of stroke. However, not all patients with unruptured cerebral aneurysms are hypertensive. In the DOCA-salt rats the increase in body water-free Na+ storage associated with hypertension is suggested. We hypothesized that in oophorectomized rats fed a high salt diet, body water-free Na+ accumulation may be increased, leading to the formation of cerebral aneurysms. To address the relationship between the increase in the body Na+-to-water ratio that characterizes water-free Na+ accumulation and the formation of cerebral aneurysms, we focused on vascular Na efflux pump Na+/K+ ATPase. Methods— Thirteen-week old female Sprague-Dawley rats subjected to carotid artery ligation were fed a high-salt diet and divided into 3 groups; a group without- (HSD) and another with bilateral oophorectomy (HSD/OVX) and a 3rd group that underwent additional renal artery ligation (HSD/OVX/RL) to induce hypertension. Results— Compared to HSD rats, the incidence of cerebral aneurysms and the body Na+-to-water ratio were significantly higher in HSD/OVX- and HSD/OVX/RL rats independent of hypertension. In their aneurysmal wall, ATP1α2, a subtype of Na+/K+-ATPase were down-regulated and renin-angiotensin system- and inflammation related molecules were up-regulated. In HSD/OVX/RL rats treatment with low dose olmesartan up-regulated ATP1α2 without affecting blood pressure and reduced the body Na+-to-water ratio and the incidence of cerebral aneurysm formation. Conclusions— These results suggest that a reduction in the vascular Na efflux pump during excessive salt intake in oophorectomized rats may be associated with the increase in water-free Na+ accumulation directing to cerebral aneurysm formation.

Modeling the Geometry, Hemodynamics and Tissue Mechanics of Cerebral Aneurysms

2004 ◽  
Author(s):  
Baoshun Ma ◽  
Robert Harbaugh ◽  
Jia Lu ◽  
Madhavan Raghavan
Keyword(s):  
Shear Stress ◽  
Mechanical Stress ◽  
Cerebral Aneurysm ◽  
Residence Time ◽  
Cerebral Aneurysms ◽  
Lesion Size ◽  
Tissue Mechanics ◽  
Particle Residence Time ◽  
Aneurysm Wall ◽  
Geometric Size

The relationship between cerebral aneurysm geometry and biomechanics was investigated. Human cerebral aneurysm geometry was reconstructed from computed tomography angiography (CTA) and refined. Various indices of global geometric (size and shape) features were computed based on differential and computational geometry techniques. Computational fluid dynamics (CFD) simulations were performed to model both steady and pulsatile blood flow in the aneurysm and surrounding vasculature. Hemodynamic indices such as wall shear stress, pressure and particle residence time were obtained. Nonlinear finite element method (FEM) and a reported finite strain constitutive model were employed to estimate the distribution of mechanical stress in the aneurysm wall under static pressure. Shear stress, sac pressure and mechanical stress correlated better with lesion shape while particle residence time correlated better with lesion size.

scholarly journals Role of diet-related factors in cerebral aneurysm formation and rupture

2019 ◽  
pp. 119-126
Author(s):  
Anna Czekajło
Keyword(s):  
Blood Pressure ◽  
Cerebral Aneurysm ◽  
Cerebral Aneurysms ◽  
Renin Angiotensin System ◽  
Vascular Wall ◽  
Caffeine Consumption ◽  
Related Factors ◽  
Hemodynamic Stress ◽  
Aneurysm Formation

Cerebral aneurysms (CAs) are dilations of the wall of an artery in the brain filled with blood. The prevalence of unrupted CA in general population is estimated at approximately 3%. Ruptured aneurysms are the cause of 85% of spontaneous subarachnoid hemorrhage (SAH) cases. The formation of cerebral aneurysms results from various factors, including chronic inflammation, hemodynamic stress and vascular wall remodeling. Reactive oxygen species may induce the endothelial dysfunction possibly through the activation of Nuclear Factor Kappa-B, which is a key regulator of the proinflammatory genes. Hypertension may additionally increase the hemodynamic stress and activate the local renin-angiotensin system. The aim of this review was to assess the role of selected diet-related factors in the formation and rupture of cerebral aneurysms. It appears that inadequate intake of dietary antioxidants, hyperhomocysteinemia, hypertension (including incidental elevated blood pressure) and alcohol consumption may increase the risk of intracranial aneurysms. Individuals at high risk of CA formation and/or rupture should consume adequate amounts of antioxidant vitamins (vitamin C, vitamin E and carotenoids), B vitamins (vitamin B6, vitamin B12 and folate), flavonoids and n-3 fatty acids, limit alcohol and caffeine consumption and regularly control their blood pressure. Vegetables, fruits, grains, pulses, nuts and fish, as well as herbs, spices and tea, should be the major components of the daily diet. Due to the synergistic effect of various dietary components on health, Mediterranean diet or Dietary Approach to Stop Hypertension (DASH) diet, as they meet abovementioned requirements and have high anti-inflammatory potential, are thus recommended for the prevention of cerebral aneurysm formation and rupture.

A Simulation Study on the Growth of Cerebral Aneurysms

2007 ◽  
Author(s):  
Y. Shimogonya ◽  
Y. Imai ◽  
T. Ishikawa ◽  
T. Yamaguchi
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebrovascular Disease ◽  
Cerebral Aneurysm ◽  
Simulation Study ◽  
Arterial Wall ◽  
Clinical Medicine ◽  
Cerebral Aneurysms ◽  
Important Disease

Cerebral aneurysm is a cerebrovascular disease characterized by the local balloon-shaped expansion of the arterial wall. It is an extremely important disease on the clinical medicine, because the rupture of the cerebral aneurysm causes serious pathologic conditions such as the subarachnoid hemorrhage.

scholarly journals Cigarette Smoke and Inflammation: Role in Cerebral Aneurysm Formation and Rupture

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Nohra Chalouhi ◽  
Muhammad S. Ali ◽  
Robert M. Starke ◽  
Pascal M. Jabbour ◽  
Stavropoula I. Tjoumakaris ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cerebral Aneurysm ◽  
Cigarette Smoke ◽  
Cerebral Aneurysms ◽  
Smoke Exposure ◽  
Rational Approach ◽  
Cigarette Smoke Exposure ◽  
Critical Pathway ◽  
Aneurysm Formation ◽  
Established Risk Factor

Smoking is an established risk factor for subarachnoid hemorrhage yet the underlying mechanisms are largely unknown. Recent data has implicated a role of inflammation in the development of cerebral aneurysms. Inflammation accompanying cigarette smoke exposure may thus be a critical pathway underlying the development, progression, and rupture of cerebral aneurysms. Various constituents of the inflammatory response appear to be involved including adhesion molecules, cytokines, reactive oxygen species, leukocytes, matrix metalloproteinases, and vascular smooth muscle cells. Characterization of the molecular basis of the inflammatory response accompanying cigarette smoke exposure will provide a rational approach for future targeted therapy. In this paper, we review the current body of knowledge implicating cigarette smoke-induced inflammation in cerebral aneurysm formation/rupture and attempt to highlight important avenues for future investigation.

Fluid structure interaction model for biological systems in the presence of magnetic field

2016 ◽  
Vol 30 (28n29) ◽  
pp. 1640005 ◽  
Author(s):  
Asim Aziz ◽  
Muhammad Shoaib
Keyword(s):  
Magnetic Field ◽  
Cerebral Aneurysm ◽  
Arterial Wall ◽  
Flow Behavior ◽  
Cerebral Aneurysms ◽  
Interaction Model ◽  
Wall Structure ◽  
Electrically Conducting ◽  
Wall Movement ◽  
Mathematical Equations

In the present paper a one-dimensional mathematical model of a cerebral aneurysm is considered. The model combines the interaction between the arterial wall structure, blood pressure and the cerebral spinal fluid (CSF) that is around the aneurysm. CSF is considered electrically conducting in the presence of a uniform magnetic field. Therefore, it may be possible to control pressure and its flow behavior by using an appropriate magnetic field. Hence, such studies have potential for the treatment of Cerebral aneurysms, diseases of heart and blood vessels. The modeled mathematical equations are solved algebraically and the displacement of the arterial wall is plotted to visualize the wall movement. It is evident from the graphs the inclusion of magnetic field reduce the movement of the arterial wall and in turn prevent the rupture of the cerebral aneurysm. The solution is also investigated using computational tools for various other parameters involve in the model.

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