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      Association between hemodynamics, morphology, and rupture risk of intracranial aneurysms: a computational fluid modeling study

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          Abstract

          The objective of the study was to examine the correlations between intracranial aneurysm morphology and wall shear stress (WSS) to identify reliable predictors of rupture risk. Seventy-two intracranial aneurysms (41 ruptured and 31 unruptured) from 63 patients were studied retrospectively. All aneurysms were divided into two categories: narrow (aspect ratio ≥1.4) and wide-necked (aspect ratio <1.4 or neck width ≥4 mm). Computational fluid dynamics was used to determine the distribution of WSS, which was analyzed between different morphological groups and between ruptured and unruptured aneurysms. Sections of the walls of clipped aneurysms were stained with hematoxylin–eosin, observed under a microscope, and photographed. Ruptured aneurysms were statistically more likely to have a greater low WSS area ratio (LSAR) ( P = 0.001) and higher aneurysms parent WSS ratio ( P = 0.026) than unruptured aneurysms. Narrow-necked aneurysms were statistically more likely to have a larger LSAR ( P < 0.001) and lower values of MWSS ( P < 0.001), mean aneurysm-parent WSS ratio ( P < 0.001), HWSS ( P = 0.012), and the highest aneurysm-parent WSS ratio ( P < 0.001) than wide-necked aneurysms. The aneurysm wall showed two different pathological changes associated with high or low WSS in wide-necked aneurysms. Aneurysm morphology could affect the distribution and magnitude of WSS on the basis of differences in blood flow. Both high and low WSS could contribute to focal wall damage and rupture through different mechanisms associated with each morphological type.

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          The online version of this article (doi:10.1007/s10072-017-2904-y) contains supplementary material, which is available to authorized users.

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          Most cited references31

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          Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques.

          Dysregulated extracellular matrix (ECM) metabolism may contribute to vascular remodeling during the development and complication of human atherosclerotic lesions. We investigated the expression of matrix metalloproteinases (MMPs), a family of enzymes that degrade ECM components in human atherosclerotic plaques (n = 30) and in uninvolved arterial specimens (n = 11). We studied members of all three MMP classes (interstitial collagenase, MMP-1; gelatinases, MMP-2 and MMP-9; and stromelysin, MMP-3) and their endogenous inhibitors (TIMPs 1 and 2) by immunocytochemistry, zymography, and immunoprecipitation. Normal arteries stained uniformly for 72-kD gelatinase and TIMPs. In contrast, plaques' shoulders and regions of foam cell accumulation displayed locally increased expression of 92-kD gelatinase, stromelysin, and interstitial collagenase. However, the mere presence of MMP does not establish their catalytic capacity, as the zymogens lack activity, and TIMPs may block activated MMPs. All plaque extracts contained activated forms of gelatinases determined zymographically and by degradation of 3H-collagen type IV. To test directly whether atheromata actually contain active matrix-degrading enzymes in situ, we devised a method which allows the detection and microscopic localization of MMP enzymatic activity directly in tissue sections. In situ zymography revealed gelatinolytic and caseinolytic activity in frozen sections of atherosclerotic but not of uninvolved arterial tissues. The MMP inhibitors, EDTA and 1,10-phenanthroline, as well as recombinant TIMP-1, reduced these activities which colocalized with regions of increased immunoreactive MMP expression, i.e., the shoulders, core, and microvasculature of the plaques. Focal overexpression of activated MMP may promote destabilization and complication of atherosclerotic plaques and provide novel targets for therapeutic intervention.
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            Saccular intracranial aneurysm: pathology and mechanisms.

            Saccular intracranial aneurysms (sIA) are pouch-like pathological dilatations of intracranial arteries that develop when the cerebral artery wall becomes too weak to resist hemodynamic pressure and distends. Some sIAs remain stable over time, but in others mural cells die, the matrix degenerates, and eventually the wall ruptures, causing life-threatening hemorrhage. The wall of unruptured sIAs is characterized by myointimal hyperplasia and organizing thrombus, whereas that of ruptured sIAs is characterized by a decellularized, degenerated matrix and a poorly organized luminal thrombus. Cell-mediated and humoral inflammatory reaction is seen in both, but inflammation is clearly associated with degenerated and ruptured walls. Inflammation, however, seems to be a reaction to the ongoing degenerative processes, rather than the cause. Current data suggest that the loss of mural cells and wall degeneration are related to impaired endothelial function and high oxidative stress, caused in part by luminal thrombosis. The aberrant flow conditions caused by sIA geometry are the likely cause of the endothelial dysfunction, which results in accumulation of cytotoxic and pro-inflammatory substances into the sIA wall, as well as thrombus formation. This may start the processes that eventually can lead to the decellularized and degenerated sIA wall that is prone to rupture.
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              Complex hemodynamics at the apex of an arterial bifurcation induces vascular remodeling resembling cerebral aneurysm initiation.

              Arterial bifurcation apices are common sites for cerebral aneurysms, raising the possibility that the unique hemodynamic conditions associated with flow dividers predispose the apical vessel wall to aneurysm formation. This study sought to identify the specific hemodynamic insults that lead to maladaptive vascular remodeling associated with aneurysm development and to identify early remodeling events at the tissue and cellular levels. We surgically created new branch points in the carotid vasculature of 6 female adult dogs. In vivo angiographic imaging and computational fluid dynamics simulations revealed the detailed hemodynamic microenvironment for each bifurcation, which were then spatially correlated with histologic features showing specific tissue responses. We observed 2 distinct patterns of vessel wall remodeling: (1) hyperplasia that formed an intimal pad at the bifurcation apex and (2) destructive remodeling in the adjacent region of flow acceleration that resembled the initiation of an intracranial aneurysm, characterized by disruption of the internal elastic lamina, loss of medial smooth muscle cells, reduced proliferation of smooth muscle cells, and loss of fibronectin. Strong localization of aneurysm-type remodeling to the region of accelerating flow suggests that a combination of high wall shear stress and a high gradient in wall shear stress represents a "dangerous" hemodynamic condition that predisposes the apical vessel wall to aneurysm formation.
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                Author and article information

                Contributors
                +86-13676884796 , sxrqtl@163.com , 3503340264@qq.com
                Journal
                Neurol Sci
                Neurol. Sci
                Neurological Sciences
                Springer Milan (Milan )
                1590-1874
                1590-3478
                11 March 2017
                11 March 2017
                2017
                : 38
                : 6
                : 1009-1018
                Affiliations
                [1 ]ISNI 0000 0004 1798 6662, GRID grid.415644.6, Department of Neurosurgery, , Shaoxing People’s Hospital, ; Shaoxing, 312000 Zhejiang China
                [2 ]ISNI 0000 0000 9055 7865, GRID grid.412551.6, School of Medicine, , Shaoxing University, ; Zhejiang, China
                [3 ]Department of Neurosurgery, Chongming Branch of Shanghai Xinghua Hospital, Chongming, 202150 Shanghai China
                Article
                2904
                10.1007/s10072-017-2904-y
                5486504
                28285454
                886acd59-7b63-4a01-a687-97316db0eae4
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 13 December 2016
                : 7 March 2017
                Funding
                Funded by: Zhejiang provincial science and Technology Department of public welfare technology research social development project: Application study of computing fluid dynamics and morphology in intracranial aneurysm development, rupture and treatment
                Award ID: 2014C33SA600012
                Award Recipient :
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag Italia S.r.l. 2017

                Neurosciences
                intracranial aneurysms,wall shear stress,hemodynamics,computational fluid dynamics

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