Dataset Information

Sex Differences in the Cerebral Collateral Circulation.

ABSTRACT: Premenopausal women and intact female rodents sustain smaller cerebral infarctions than males. Several sex-dependent differences have been identified as potential contributors, but many questions remain unanswered. Mice exhibit wide variation in native collateral number and diameter (collateral extent) that is dependent on differences in genetic background, aging, and other comorbidities and that contributes to their also-wide differences in infarct volume. Likewise, variation in infarct volume correlates with differences in collateral-dependent blood flow in patients with acute ischemic stroke. We examined whether extent of pial collateral arterioles and posterior communicating collateral arteries (PComAs) differ depending on sex in young, aged, obese, hypertensive, and genetically different mice. We combined new data with meta-analysis of our previously published data. Females of C57BL/6J (B6) and BALB/cByJ (BC) strains sustained smaller infarctions than males after permanent MCA occlusion. This protection was unchanged in BC mice after introgression of the B6 allele of Dce1, the major genetic determinant of variation in pial collaterals among mouse strains. Consistent with this, collateral extent in these and other strains did not differ with sex. Extent of PComAs and primary cerebral arteries also did not vary with sex. No dimorphism was evident for loss of pial collateral number and/or diameter (collateral rarefaction) caused by aging, obesity, and hypertension, nor for collateral remodeling after pMCAO. However, rarefaction was greater in females with long-standing hypertension. We conclude that smaller infarct volume in female mice is not due to greater collateral extent, greater remodeling, or less rarefaction caused by aging, obesity, or hypertension.

SUBMITTER: Faber JE

PROVIDER: S-EPMC5429998 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Sex Differences in the Cerebral Collateral Circulation.

Faber James E JE Moore Scott M SM Lucitti Jennifer L JL Aghajanian Amir A Zhang Hua H

Translational stroke research 20161114 3

Premenopausal women and intact female rodents sustain smaller cerebral infarctions than males. Several sex-dependent differences have been identified as potential contributors, but many questions remain unanswered. Mice exhibit wide variation in native collateral number and diameter (collateral extent) that is dependent on differences in genetic background, aging, and other comorbidities and that contributes to their also-wide differences in infarct volume. Likewise, variation in infarct volume ...[more]

PMID: 27844273

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Project description:Following an arterial occlusion outward remodeling of pre-existent inter-connecting arterioles occurs by proliferation of vascular smooth muscle and endothelial cells. This is initiated by deformation of the endothelial cells through increased pulsatile fluid shear stress (FSS) caused by the steep pressure gradient between the high pre-occlusive and the very low post-occlusive pressure regions that are interconnected by collateral vessels. Shear stress leads to the activation and expression of all NOS isoforms and NO production, followed by endothelial VEGF secretion, which induces MCP-1 synthesis in endothelium and in the smooth muscle of the media. This leads to attraction and activation of monocytes and T-cells into the adventitial space (peripheral collateral vessels) or attachment of these cells to the endothelium (coronary collaterals). Mononuclear cells produce proteases and growth factors to digest the extra-cellular scaffold and allow motility and provide space for the new cells. They also produce NO from iNOS, which is essential for arteriogenesis. The bulk of new tissue production is carried by the smooth muscles of the media, which transform their phenotype from a contractile into a synthetic and proliferative one. Important roles are played by actin binding proteins like ABRA, cofilin, and thymosin beta 4 which determine actin polymerization and maturation. Integrins and connexins are markedly up-regulated. A key role in this concerted action which leads to a 2-to-20 fold increase in vascular diameter, depending on species size (mouse versus human) are the transcription factors AP-1, egr-1, carp, ets, by the Rho pathway and by the Mitogen Activated Kinases ERK-1 and -2. In spite of the enormous increase in tissue mass (up to 50-fold) the degree of functional restoration of blood flow capacity is incomplete and ends at 30% of maximal conductance (coronary) and 40% in the vascular periphery. The process of arteriogenesis can be drastically stimulated by increases in FSS (arterio-venous fistulas) and can be completely blocked by inhibition of NO production, by pharmacological blockade of VEGF-A and by the inhibition of the Rho-pathway. Pharmacological stimulation of arteriogenesis, important for the treatment of arterial occlusive diseases, seems feasible with NO donors.

Project description:BackgroundIn-stent restenosis is a crucial problem after carotid artery stenting, but the exact predictors of in-stent restenosis remain unclear. We aimed to evaluate the effect of cerebral collateral circulation on in-stent restenosis after carotid artery stenting and to establish a clinical prediction model for in-stent restenosis.MethodsThis retrospective case-control study enrolled 296 patients with severe carotid artery stenosis of C1 segment (≥70%) who underwent stent therapy from June 2015 to December 2018. Based on follow-up data, the patients were divided into the in-stent restenosis and no in-stent restenosis groups. The collateral circulation of the brain was graded according to the criteria of the American Society for Interventional and Therapy Neuroradiology/Society for Interventional Radiology (ASITN/SIR). Clinical data were collected, such as age, sex, traditional vascular risk factors, blood cell count, high-sensitivity C-reactive protein, uric acid, stenosis degree before stenting and residual stenosis rate, and medication after stenting. Binary logistic regression analysis was performed to identify potential predictors of in-stent restenosis, and a clinical prediction model for in-stent restenosis after carotid artery stenting was established.ResultsBinary logistic regression analysis showed that poor collateral circulation was an independent predictor of in-stent restenosis (P=0.003). We also found that a 1% increase in residual stenosis rate was associated with a 9% increase in the risk of in-stent restenosis (P=0.02). Ischemic stroke history (P=0.03), family history of ischemic stroke (P<0.001), in-stent restenosis history (P<0.001), and nonstandard medication after stenting (P=0.04) were predictors of in-stent restenosis. The risk of in-stent restenosis was lowest when the residual stenosis rate was 12.5% after carotid artery stenting. Furthermore, we used some significant parameters to construct a binary logistic regression prediction model for in-stent restenosis after carotid artery stenting in the form of a nomogram.ConclusionsCollateral circulation is an independent predictor of in-stent restenosis after successful carotid artery stenting, and the residual stenosis rate tends to be below 12.5% to reduce restenosis risk. The standard medication should be strictly carried out for patients after stenting to prevent in-stent restenosis.

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Project description:Collateral circulation in the circle of Willis (CoW), closely associated with disease mechanisms and treatment outcomes, can be effectively investigated using one-dimensional-zero-dimensional hemodynamic simulations. As the entire cardiovascular system is considered in the simulation, it captures the systemic effects of local arterial changes, thus reproducing collateral circulation that reflects biological phenomena. The simulation facilitates rapid assessment of clinically relevant hemodynamic quantities under patient-specific conditions by incorporating clinical data. During patient-specific simulations, the impact of clinical data uncertainty on the simulated quantities should be quantified to obtain reliable results. However, as uncertainty quantification (UQ) is time-consuming and computationally expensive, its implementation in time-sensitive clinical applications is considered impractical. Therefore, we constructed a surrogate model based on machine learning using simulation data. The model accurately predicts the flow rate and pressure in the CoW in a few milliseconds. This reduced computation time enables the UQ execution with 100 000 predictions in a few minutes on a single CPU core and in less than a minute on a GPU. We performed UQ to predict the risk of cerebral hyperperfusion (CH), a life-threatening condition that can occur after carotid artery stenosis surgery if collateral circulation fails to function appropriately. We predicted the statistics of the postoperative flow rate increase in the CoW, which is a measure of CH, considering the uncertainties of arterial diameters, stenosis parameters, and flow rates measured using the patients' clinical data. A sensitivity analysis was performed to clarify the impact of each uncertain parameter on the flow rate increase. Results indicated that CH occurred when two conditions were satisfied simultaneously: severe stenosis and when arteries of small diameter serve as the collateral pathway to the cerebral artery on the stenosis side. These findings elucidate the biological aspects of cerebral circulation in terms of the relationship between collateral flow and CH.

Dataset Information

Sex Differences in the Cerebral Collateral Circulation.

Publications

Sex Differences in the Cerebral Collateral Circulation.

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