Histopathology of Cerebral Aneurysms

Stehbens, William E.

doi:10.1001/archneur.1963.00460030056005

Cited by 193 publications

(71 citation statements)

References 17 publications

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“…Aneurysm formation is an active remodeling process characterized by loss of the internal elastic lamina, media layer thinning, and bulge formation, which requires degradation of extracellular matrix (16,43). Similarly, rupture of a vulnerable plaque requires degradation of extracellular matrix in the fibrous cap (38).…”

Section: Matrix Remodeling By Positive Wssg and High Wssmentioning

confidence: 99%

Differential gene expression by endothelial cells under positive and negative streamwise gradients of high wall shear stress

Dolan

Meng

Sim

et al. 2013

American Journal of Physiology-Cell Physiology

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, and flow acceleration and deceleration in the branches create positive and negative streamwise gradients in WSS (WSSG), respectively. Intracranial aneurysms tend to form in regions with high WSS and positive WSSG. However, little is known about the responses of endothelial cells (ECs) to either positive or negative WSSG under high WSS conditions. We used cDNA microarrays to profile gene expression in cultured ECs exposed to positive or negative WSSG for 24 h in a flow chamber where WSS varied between 3.5 and 28.4 Pa. Gene ontology and biological pathway analysis indicated that positive WSSG favored proliferation, apoptosis, and extracellular matrix processing while decreasing expression of proinflammatory genes. To determine if similar responses occur in vivo, we examined EC proliferation and expression of the matrix metalloproteinase ADAMTS1 under high WSS and WSSG created at the basilar terminus of rabbits after bilateral carotid ligation. Precise hemodynamic conditions were determined by computational fluid dynamic simulations from three-dimensional angiography and mapped on immunofluorescence staining for the proliferation marker Ki-67 and ADAMTS1. Both proliferation and ADAMTS1 were significantly higher in ECs under positive WSSG than in adjacent regions of negative WSSG. Our results indicate that WSSG elicits distinct EC gene expression profiles and particular biological pathways including increased cell proliferation and matrix processing. Such EC responses may be important in understanding the mechanisms of intracranial aneurysm initiation at regions of high WSS and positive WSSG. high wall shear stress; microarray; intracranial aneurysm initiation; vascular remodeling; spatial gradient AS THE INNERMOST LINING OF the blood vessel wall, endothelial cells (ECs) are the signal transduction interface between wall shear stress (WSS) exerted on the lining by flowing blood and the responses of underlying tissue. It is well known that endothelial structure, function, and gene expression are modulated by normal WSS (1.5-2.5 Pa) and that ECs respond differently when exposed to relatively low WSS (Ͻ0.4 Pa), and this effect is believed to play a role in atherosclerosis (21). However, endothelial responses under considerably higher WSS (Ͼ10 Pa) are not well characterized. Such high WSS occurs in arteries feeding arteriovenous fistulas (37, 42), in stenosed vessels (33, 34), in collateral arteries secondary to blockage (36, 50), and at arterial bifurcations, where high WSS predisposes intracranial vessels to aneurysm formation (24, 26).There is mounting evidence that ECs are also sensitive to spatial differences in WSS over their luminal surface, specifically to streamwise gradients in WSS [WSS gradient (WSSG)]. The effects of WSSG under low WSS have been examined in vitro in flow recirculation zones, which in vivo are prone to atherogenesis (10, 56). Under low WSS and WSSG, ECs show increased permeability (31), migration (5, 46), proliferation (46), and activation of the transcription factors NF-B, Egr-1, c-Jun, an...

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Section: Matrix Remodeling By Positive Wssg and High Wssmentioning

confidence: 99%

Differential gene expression by endothelial cells under positive and negative streamwise gradients of high wall shear stress

Dolan

Meng

Sim

et al. 2013

American Journal of Physiology-Cell Physiology

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“…It is conceivable that our experimental lesions might have a more robust response to injury than a cerebral aneurysm, since they retain all the elements of a normal arterial wall. Previous studies, however, have suggested that cerebral aneurysms possess a full repertoire of responses to injury, similar to those of the normal arterial wall 24 . In the present study, a selectively higher peripheral concentration of granulation tissue and invariable central location of residual unorganized thrombus in embolized CCA stumps indicate a centripetal pattern of healing.…”

Section: Discussionmentioning

confidence: 91%

Effects of Endothelial Injury on the Rate of Thrombus Organization in Canine Carotid Arteries Occluded with Microcoils

Abruzzo

Shengelaia²,

Workman³

et al. 2003

Interv Neuroradiol

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Thrombus organization in canine carotid arteries occluded with platinum microcoils was studied to determine if endothelial injury created with a Xenon Chloride Excimer Laser (XEL) could acclerate endovascular fibrosis. Ten common carotid artery stumps were created in ten dogs. Each of four stumps were schematically divided into four longitudinally contiguous injury zones (thermal ablation injury, non-ablative injury, proximal and distal non-injury zones) to test the effects of ablative and non-ablative injury and to establish a set of internal controls that would account for proximity to circulating blood at the ostium of the occluded artery. Following XEL irradiation of the endothelium through an arteriotomy, each stump was embolized with microcoils. Four control stumps were subjected to sham laser procedures, and embolized in an identical fashion. Two additional stumps were embolized in the absence of sham surgery. Angiographic, gross and histologic analysis was performed after four weeks. Specimens of freshly clotted whole blood mixed with microcoils were used as an additional control. In irradiated stumps and non-irradiated stumps (sham and embolization only), angiography revealed no evidence of coil compaction or recanalization. In all irradiated stumps the thermal ablation zone contained fibrous tissue and neovascularity without unorganized thrombus. The other zones in the irradiated stumps were indistingnishable from each other and from all zones in the non-irradiated sham stumps, containing primarily unorganized thrombus. Stumps embolized in the absence of sham surgery were filled with material that was grossly and microscopically identical to specimens of freshly clotted whole blood containing microcoils. The results indicate that thermal ablation injury of the endothelium accelerates thrombus organization in canine carotid arteries occluded with platinum microcoils.

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“…8,18) Nonatherosclerotic aneurysms unrelated to the branching zones can be classified into the following four types, based on the pathological patterns of the internal elastic lamina and the state of the intima: classic dissecting aneurysm (widespread disruption of the internal elastic lamina without intimal thickening), segmental ectasia (stretched/fragmented internal elastic lamina with intimal thickening), dolichoectatic dissecting aneurysm (fragmented internal elastic lamina and multiple dissections of the thickened intima), and saccular aneurysm (minimal disruption of the internal elastic lamina without intimal thickening). 13) In the present case, the histological examination demonstrated a saccular aneurysm, although hemodynamic stress was unlikely to have affected the formation of the aneurysm according to the angiographical findings.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Ruptured Spontaneous Saccular Aneurysm in the Central Artery of the Middle Cerebral Artery Using Bypass Surgery Combined With Trapping -Case Report-

Saitō

Ogasawara

Kubo

et al. 2007

Neurol. Med. Chir.(Tokyo)

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Histopathology of Cerebral Aneurysms

Cited by 193 publications

References 17 publications

Differential gene expression by endothelial cells under positive and negative streamwise gradients of high wall shear stress

Differential gene expression by endothelial cells under positive and negative streamwise gradients of high wall shear stress

Effects of Endothelial Injury on the Rate of Thrombus Organization in Canine Carotid Arteries Occluded with Microcoils

Treatment of Ruptured Spontaneous Saccular Aneurysm in the Central Artery of the Middle Cerebral Artery Using Bypass Surgery Combined With Trapping -Case Report-

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