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Gerhard A Holzapfel - One of the best experts on this subject based on the ideXlab platform.
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influence of medial collagen organization and axial in situ stretch on saccular Cerebral Aneurysm growth
Journal of Biomechanical Engineering-transactions of The Asme, 2009Co-Authors: Thomas Eriksson, Martin Kroon, Gerhard A HolzapfelAbstract:A model for saccular Cerebral Aneurysm growth, proposed by Kroon and Holzapfel (2007, "A Model for Saccular Cerebral Aneurysm Growth in a Human Middle Cerebral Artery," J. Theor. Biol., 247, pp. 77 ...
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a model for saccular Cerebral Aneurysm growth by collagen fibre remodelling
Journal of Theoretical Biology, 2007Co-Authors: Martin Kroon, Gerhard A HolzapfelAbstract:The first structural model for saccular Cerebral Aneurysm growth is proposed. It is assumed that the development of the Aneurysm is accompanied by a loss of the media, and that only collagen fibres provide load-bearing capacity to the Aneurysm wall. The Aneurysm is modelled as an axisymmetric multi-layered membrane, exposed to an inflation pressure. Each layer is characterized by an orientation angle, which changes between different layers. The collagen fibres and fibroblasts within a specific layer are perfectly aligned. The growth and the morphological changes of the Aneurysm are accomplished by the turnover of collagen. Fibroblasts are responsible for collagen production, and the related deformations are assumed to govern the collagen production rate. There are four key parameters in the model: a normalized pressure, the number of layers in the wall, an exponent in the collagen mass production rate law, and the pre-stretch under which the collagen is deposited. The influence of the model parameters on the Aneurysmal response is investigated, and a stability analysis is performed. The model is able to predict clinical observations and mechanical test results, for example, in terms of predicted Aneurysm size, shape, wall stress and wall thickness.
Nobuo Hashimoto - One of the best experts on this subject based on the ideXlab platform.
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Pathogenesis of Cerebral Aneurysms: evidence using experimentally induced Cerebral Aneurysm models
2010Co-Authors: Shunichi Fukuda, Nobuo Hashimoto, Kazuhiko Nozaki, Masaaki NishimuraAbstract:Background: Cerebral saccular Aneurysm is a major cause of subarachnoid hemorrhage, one of the cerebrovascular diseases with the highest mortality. The mechanisms underlying the development of Aneurysm, however, still remain unclear. Objective: The authors have made a series of reports on an animal model of experimentally induced Cerebral Aneurysms that resemble human Cerebral Aneurysms in their location and morphology. The objective of this brief review is to introduce our evidence about the pathogenesis of Cerebral Aneurysms using the experimentally induced Cerebral Aneurysm model, particularly focused upon the role of nitric oxide (NO) and shear stress on degenerative changes of the arterial wall during Aneurysm development. Methods: We first introduce methods of Aneurysm-inducing surgery, and then refer to morphological analysis of Aneurysmal induction. Next, we explain the association between Aneurysmal development and shear stress and NO. Finally, we show several mechanisms of Aneurysmal development using genetically modified animals. Results and conclusion: In our animal model, Cerebral Aneurysms are induced in rats, monkeys, and mice by ligation of the unilateral common carotid artery and renal hypertension, suggesting that an increase in hemodynamic stress is a key requirement for the Aneurysm development. Our morphological and molecular studies suggest that increased wall shear stress, iNOS-derived NO, MMP-2 & 9, cathepsin B, NF-κB, interleukin-1β, and endothelin B receptor are associated with the progression of Cerebral Aneurysms. Statin and Nifedipine may be possible drugs for the prevention of Cerebral Aneurysm development.
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Toll-like receptor 4 expression during Cerebral Aneurysm formation: Laboratory investigation
Journal of neurosurgery, 2010Co-Authors: Tomohiro Aoki, Masaki Nishimura, Ryota Ishibashi, Hiroharu Kataoka, Yasushi Takagi, Nobuo HashimotoAbstract:Object The pathophysiological origin of Cerebral Aneurysms is closely associated with chronic inflammation in arterial walls. Recently, the authors identified nuclear factor-kappa B (NF-κB) as a key mediator of Cerebral Aneurysm formation and progression. Because Toll-like receptor 4 (TLR4) stimulates NF-κB activation in arterial walls in atherosclerosis, the authors hypothesize that TLR4 expresses in Cerebral Aneurysms and contributes to the activation of NF-κB in Cerebral Aneurysm walls. Methods Cerebral Aneurysms were induced in male Sprague-Dawley rats. Expression of TLRs in Cerebral Aneurysm walls was assessed using reverse transcriptase polymerase chain reaction (RT-PCR). The expression of TLR4 was examined using RT-PCR, immunohistochemical studies, and Western blotting. To assess TLR4 dependency on NF-κB activation, double immunostaining and a study using NF-κB-deficient mice were done. Finally, TLR4 expression in human Cerebral Aneurysm walls was assessed using immunohistochemical studies. Results In Cerebral Aneurysm walls, TLR1, -4, -5, -6, -10, and -11 were expressed. Among them, TLR4 and TLR10 expression changed during Cerebral Aneurysm formation. Expression of TLR4 was predominantly in the endothelial cell layer of Cerebral Aneurysm walls, and was transitionally upregulated at the early stage of Cerebral Aneurysm formation. The TLR4 expression coincided well with NF-κB activation. In human Cerebral Aneurysms, TLR4 was also expressed in the endothelial cell layer, as it was in rats. Conclusions Toll-like receptor 4 was expressed in Cerebral Aneurysm walls both in rats and humans. This receptor may play a crucial role in Cerebral Aneurysm formation through NF-κB activation in endothelial cells. The results of the present study will shed new light on the pathogenesis of Cerebral Aneurysm formation.
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impact of monocyte chemoattractant protein 1 deficiency on Cerebral Aneurysm formation
Stroke, 2009Co-Authors: Tomohiro Aoki, Ryota Ishibashi, Hiroharu Kataoka, Kazuhiko Nozaki, Kensuke Egashira, Nobuo HashimotoAbstract:Background and Purpose— Recent studies have suggested that chronic inflammation actively participates in Cerebral Aneurysm (CA) formation. Macrophages accumulate in CA walls and express proinflamma...
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The efficacy of apolipoprotein E deficiency in Cerebral Aneurysm formation.
International journal of molecular medicine, 2008Co-Authors: Tomohiro Aoki, Hiroharu Kataoka, Yasushi Takagi, Takuya Moriwaki, Jiho Yang, Kazuhiko Nozaki, Nobuo HashimotoAbstract:Subarachnoid hemorrhage due to the rupture of a Cerebral Aneurysm is a life-threatening disease. Despite this, the detailed mechanisms underlying the initiation and progression of Cerebral Aneurysm are unclear. The relation of hypercholesterolemia and apolipoprotein E (ApoE) to Cerebral Aneurysm formation, has been unclear until now. We used, in the present study, a previously established Cerebral Aneurysm model of rats and mice whose histological features were closely similar to human Cerebral Aneurysms. ApoE protein was expressed mainly in the endothelial cells of arterial walls both in control arteries and Cerebral Aneurysms. The expression of ApoE was reduced during Aneurysm formation in the immunohistochemistry. The mRNA expression of ApoE in arterial walls was not different between the controls and Cerebral Aneurysms. Owing to the deficiency of ApoE, mice presented marked hypercholesterolemia, but there was no difference in Cerebral Aneurysm formation. In the present study, we clarified that ApoE was not responsible for Cerebral Aneurysm formation.
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nf κb is a key mediator of Cerebral Aneurysm formation
Circulation, 2007Co-Authors: Tomohiro Aoki, Ryota Ishibashi, Hiroharu Kataoka, Takuya Moriwaki, Kazuhiko Nozaki, Munehisa Shimamura, Hironori Nakagami, Kouji Wakayama, Ryuichi Morishita, Nobuo HashimotoAbstract:Background— Subarachnoid hemorrhage caused by the rupture of Cerebral Aneurysm (CA) remains a life-threatening disease despite recent diagnostic and therapeutic advancements. Recent studies strongl...
Giuseppe Lanzino - One of the best experts on this subject based on the ideXlab platform.
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comparative effectiveness of unruptured Cerebral Aneurysm therapies propensity score analysis of clipping versus coiling
Stroke, 2013Co-Authors: Jennifer S Mcdonald, Giuseppe Lanzino, Robert J Mcdonald, Jiaquan Fan, David F Kallmes, Harry J. CloftAbstract:Background and Purpose—Endovascular therapy has increasingly become the most common treatment for unruptured Cerebral Aneurysms in the United States. We evaluated a national, multi-hospital database to examine recent utilization trends and compare periprocedural outcomes between clipping and coiling treatments of unruptured Aneurysms. Methods—The Premier Perspective database was used to identify patients hospitalized between 2006 to 2011 for unruptured Cerebral Aneurysm who underwent clipping or coiling therapy. A logistic propensity score was generated for each patient using relevant patient, procedure, and hospital variables, representing the probability of receiving clipping. Covariate balance was assessed using conditional logistic regression. Following propensity score adjustment using 1:1 matching methods, the risk of in-hospital mortality and morbidity was compared between clipping and coiling cohorts. Results—A total of 4899 unruptured Aneurysm patients (1388 clipping, 3551 coiling) treated at 120...
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Treatment Options for Unruptured Cerebral Aneurysm.
Current treatment options in neurology, 2004Co-Authors: David Z. Wang, Huan Wang, Kenneth Fraser, Giuseppe LanzinoAbstract:The management of unruptured Cerebral Aneurysm is controversial. Because the natural history of unruptured Cerebral Aneurysm is not well defined, the best management strategy is unclear. The current consensus on the management of unruptured Cerebral Aneurysm includes observation, microsurgical clipping, and endovascular treatment. The methodologies used to follow up a known unruptured Aneurysm are controversial and may be dependent on the preferences of the treating physician. Most Aneurysms are managed by the neurosurgeons and interventional neuroradiologists, but neurologists often are the first to discover the unruptured Aneurysms when screening the patients for other neurologic disorders. Therefore, the knowledge on when to screen patients for and how to best manage an unruptured Aneurysm will have a direct impact on their daily practices. Unruptured Aneurysms often cause other neurologic symptoms including ischemic events, seizures, and headache. These symptoms may prompt more interventional treatment. Without a thoughtfully designed, true population-based study or randomized trial, the current best management will be based on the available literature and the temporal profile of each patient.
Harry J. Cloft - One of the best experts on this subject based on the ideXlab platform.
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comparative effectiveness of unruptured Cerebral Aneurysm therapies propensity score analysis of clipping versus coiling
Stroke, 2013Co-Authors: Jennifer S Mcdonald, Giuseppe Lanzino, Robert J Mcdonald, Jiaquan Fan, David F Kallmes, Harry J. CloftAbstract:Background and Purpose—Endovascular therapy has increasingly become the most common treatment for unruptured Cerebral Aneurysms in the United States. We evaluated a national, multi-hospital database to examine recent utilization trends and compare periprocedural outcomes between clipping and coiling treatments of unruptured Aneurysms. Methods—The Premier Perspective database was used to identify patients hospitalized between 2006 to 2011 for unruptured Cerebral Aneurysm who underwent clipping or coiling therapy. A logistic propensity score was generated for each patient using relevant patient, procedure, and hospital variables, representing the probability of receiving clipping. Covariate balance was assessed using conditional logistic regression. Following propensity score adjustment using 1:1 matching methods, the risk of in-hospital mortality and morbidity was compared between clipping and coiling cohorts. Results—A total of 4899 unruptured Aneurysm patients (1388 clipping, 3551 coiling) treated at 120...
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Risk of Cerebral angiography in patients with subarachnoid hemorrhage, Cerebral Aneurysm, and arteriovenous malformation: a meta-analysis.
Stroke, 1999Co-Authors: Harry J. Cloft, Gregory J. Joseph, Jacques E. DionAbstract:Background and Purpose—A well-defined complication rate of Cerebral angiography in patients with subarachnoid hemorrhage (SAH), Cerebral Aneurysm, and arteriovenous malformation (AVM) would be useful to physicians making decisions regarding the imaging of these patients. We sought to define a statistically significant complication rate through meta-analysis of prospective studies in the literature. Methods—Meta-analysis of 3 published prospective studies of complications in Cerebral angiography was performed to specifically define the risk of Cerebral angiography in patients presenting with SAH, Cerebral Aneurysm, and AVM. The complication rates for Cerebral angiography in patients with SAH and AVM/Aneurysm without SAH were compared with the complication rates in patients who underwent Cerebral angiography for transient ischemic attack (TIA)/ischemic stroke with use of the Fisher exact test. Results—The combined risk of permanent and transient neurological complication was significantly lower in patients ...
Robert M. Starke - One of the best experts on this subject based on the ideXlab platform.
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In vivo Cerebral Aneurysm models.
Neurosurgical focus, 2019Co-Authors: John W. Thompson, Omar Elwardany, David J. Mccarthy, Dallas Sheinberg, Carlos M. Alvarez, Ahmed Nada, Brian Snelling, Stephanie H. Chen, Samir Sur, Robert M. StarkeAbstract:Cerebral Aneurysm rupture is a devastating event resulting in subarachnoid hemorrhage and is associated with significant morbidity and death. Up to 50% of individuals do not survive Aneurysm rupture, with the majority of survivors suffering some degree of neurological deficit. Therefore, prior to Aneurysm rupture, a large number of diagnosed patients are treated either microsurgically via clipping or endovascularly to prevent Aneurysm filling. With the advancement of endovascular surgical techniques and devices, endovascular treatment of Cerebral Aneurysms is becoming the first-line therapy at many hospitals. Despite this fact, a large number of endovascularly treated patients will have Aneurysm recanalization and progression and will require retreatment. The lack of approved pharmacological interventions for Cerebral Aneurysms and the need for retreatment have led to a growing interest in understanding the molecular, cellular, and physiological determinants of Cerebral Aneurysm pathogenesis, maturation, and rupture. To this end, the use of animal Cerebral Aneurysm models has contributed significantly to our current understanding of Cerebral Aneurysm biology and to the development of and training in endovascular devices. This review summarizes the small and large animal models of Cerebral Aneurysm that are being used to explore the pathophysiology of Cerebral Aneurysms, as well as the development of novel endovascular devices for Aneurysm treatment.
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vascular smooth muscle cells in Cerebral Aneurysm pathogenesis
Translational Stroke Research, 2014Co-Authors: Robert M. Starke, Nohra Chalouhi, Dale Ding, Daniel M S Raper, Sean M Mckisic, Gary K Owens, David Hasan, Ricky Medel, Aaron S DumontAbstract:Vascular smooth muscle cells (SMC) maintain significant plasticity. Following environmental stimulation, SMC can alter their phenotype from one primarily concerned with contraction to a pro-inflammatory and matrix remodeling phenotype. This is a critical process behind peripheral vascular disease and atherosclerosis, a key element of Cerebral Aneurysm pathology. Evolving evidence demonstrates that SMCs and phenotypic modulation play a significant role in Cerebral Aneurysm formation and rupture. Pharmacological alteration of smooth muscle cell function and phenotypic modulation could provide a promising medical therapy to inhibit Cerebral Aneurysm progression. This study reviews vascular SMC function and its contribution to Cerebral Aneurysm pathophysiology.
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tumor necrosis factor α modulates Cerebral Aneurysm formation and rupture
Translational Stroke Research, 2014Co-Authors: Robert M. Starke, Nohra Chalouhi, Dale Ding, Daniel M S Raper, Gary K Owens, David Hasan, Ricky Medel, Aaron S DumontAbstract:Inflammation is a critical process behind Cerebral Aneurysm formation and rupture. Tumor necrosis factor alpha (TNF-α) is a key immune modulator that has been implicated in Cerebral Aneurysm pathophysiology. This may occur through TNF-α-mediated endothelial injury, smooth muscle cell phenotypic modulation, recruitment of macrophages, activation of chemotactic cytokines, upregulation of matrix remodeling genes, production of free radicals leading to oxidative stress, and ultimately cellular apoptosis. Recent studies have indicated that TNF-α may be a potential target for the development of novel medical therapies, but additional experimental data is needed to clarify the intricacies of TNF-α activation and its critical downstream targets in Cerebral Aneurysms. This review provides an update on the mechanisms underlying TNF-α-induced molecular modulation in Cerebral Aneurysms.
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the role of oxidative stress in Cerebral Aneurysm formation and rupture
Current Neurovascular Research, 2013Co-Authors: Robert M. Starke, Nohra Chalouhi, Muhammad S Ali, Pascal Jabbour, Stavropoula Tjoumakaris, Fernando L Gonzalez, Robert H Rosenwasser, Walter J Koch, Aaron S DumontAbstract:Oxidative stress is known to contribute to the progression of cerebrovascular disease. Additionally, oxidative stress may be increased by, but also augment inflammation, a key contributor to Cerebral Aneurysm development and rupture. Oxidative stress can induce important processes leading to Cerebral Aneurysm formation including direct endothelial injury as well as smooth muscle cell phenotypic switching to an inflammatory phenotype and ultimately apoptosis. Oxidative stress leads to recruitment and invasion of inflammatory cells through upregulation of chemotactic cytokines and adhesion molecules. Matrix metalloproteinases can be activated by free radicals leading to vessel wall remodeling and breakdown. Free radicals mediate lipid peroxidation leading to atherosclerosis and contribute to hemodynamic stress and hypertensive pathology, all integral elements of Cerebral Aneurysm development. Preliminary studies suggest that therapies targeted at oxidative stress may provide a future beneficial treatment for Cerebral Aneurysms, but further studies are indicated to define the role of free radicals in Cerebral Aneurysm formation and rupture. The goal of this review is to assess the role of oxidative stress in Cerebral Aneurysm pathogenesis.
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cigarette smoke and inflammation role in Cerebral Aneurysm formation and rupture
Mediators of Inflammation, 2012Co-Authors: Nohra Chalouhi, Robert M. Starke, Muhammad S Ali, Pascal Jabbour, Stavropoula Tjoumakaris, Fernando L Gonzalez, Robert H Rosenwasser, Walter J Koch, Aaron S DumontAbstract: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.