The clinical manifestations and pathophysiology of cerebral small vessel disease

Zhang, Ai-Juan; Yu, Xinjun; Wang, Mei

doi:10.1007/s12264-010-1210-y

Cited by 33 publications

(27 citation statements)

References 57 publications

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“…All of these endothelial behaviors are important for the remodeling of matrix, ingrowth of new vessels during wound healing, and for the interaction of native endothelial cells with implanted scaffolds. Recent publications have also reported that dysregulation of the endothelium would result in the modification of the extracellular matrix (ECM) and thickness and pliability of the vascular basement membrane 4, 32–36…”

Section: Discussionmentioning

confidence: 99%

Influence of membrane cholesterol and substrate elasticity on endothelial cell spreading behavior

Hong

Ersoy

Sun

et al. 2012

J Biomedical Materials Res

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Interactions between implanted materials and the surrounding host cells critically affect the fate of bioengineered materials. In this study, the biomechanical response of bovine aortic endothelial cells (BAECs) with different membrane cholesterol levels to polyacrylamide (PA) gels was investigated by measuring cell adhesion and spreading behaviors at varying PA elasticity. The elasticity of gel substrates was manipulated by cross-linker content. Type I collagen (COL1) was coated on PA gel to provide a biologically functional environment for cell spreading. Precise quantitative characterization of changes in cell area and perimeter of cells across two treatments and three bioengineered substrates were determined using a customized software developed for computational image analysis. We found that the initial response of endothelial cells to changes in substrate elasticity was determined by membrane cholesterol levels, and that the extent of endothelial cell spreading increases with membrane cholesterol content. All of the BAECs with different cholesterol levels showed little growth on substrates with elasticity below 20 kPa, but increased spreading at higher substrate elasticity. Cholesterol-depleted cells were consistently smaller than control and cholesterol-enriched cells regardless of substrate elasticity. These observations indicate that membrane-cholesterol plays an important role in cell spreading on soft materials constructed with appropriate elasticity.

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Section: Discussionmentioning

confidence: 99%

Influence of membrane cholesterol and substrate elasticity on endothelial cell spreading behavior

Hong

Ersoy

Sun

et al. 2012

J Biomedical Materials Res

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“…Large (300–400 μm diameter) synthetic macrospheres induce a large lesion similar to that produced by permanent occlusion of the MCA. However, small (<50 μm) microspheres induce smaller injuries similar to the multifocal infarcts of cerebral small-vessel disease [56, 66] , which accounts for 20%–30% of cases of ischemic stroke [67] . If the spheres used are small enough to penetrate arteries, the extent of infarction and neurological deficit correlates well with the distribution and number of trapped spheres.…”

Section: Ischemic Stroke Modelsmentioning

confidence: 99%

Experimental animal models and inflammatory cellular changes in cerebral ischemic and hemorrhagic stroke

2015

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Stroke, including cerebral ischemia, intracerebral hemorrhage, and subarachnoid hemorrhage, is the leading cause of long-term disability and death worldwide. Animal models have greatly contributed to our understanding of the risk factors and the pathophysiology of stroke, as well as the development of therapeutic strategies for its treatment. Further development and investigation of experimental models, however, are needed to elucidate the pathogenesis of stroke and to enhance and expand novel therapeutic targets. In this article, we provide an overview of the characteristics of commonly-used animal models of stroke and focus on the inflammatory responses to cerebral stroke, which may provide insights into a framework for developing effective therapies for stroke in humans.

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“…Chronic cerebral hypoxic-ischemic injury, an important factor contributing to many age-related neurodegenerative disorders, 11–13 also appears to involve HIF-1 related pathways. 14 Interestingly, HIF-1 activation is also reduced in aging.…”

Section: Introductionmentioning

confidence: 99%

Deferoxamine, Cerebrovascular Hemodynamics, and Vascular Aging

Sorond

Tan

LaRose

et al. 2015

Stroke

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Background and Purpose Iron chelation therapy is emerging as a novel neuroprotective strategy. The mechanisms of neuroprotection are diverse and include both neuronal and vascular pathways. We sought to examine the effect of iron chelation on cerebrovascular function in healthy aging and to explore whether HIF-1 activation may be temporally correlated with vascular changes Methods We assessed cerebrovascular function (autoregulation, vasoreactivity, neurovascular coupling) and serum concentrations of vascular endothelial growth factor (VEGF) and erythropoietin (EPO), as representative measures of HIF-1 activation, during 6 hours of deferoxamine (DFO) infusion in healthy 24 young and 24 older volunteers in a randomized, blinded, placebo-controlled cross-over study design. Cerebrovascular function was assessed using the transcranial Doppler ultrasound. VEGF and EPO serum protein assays were conducted using the Meso Scale Discovery platform. Results DFO elicited a strong age- and time-dependent increase in the plasma concentrations of EPO and VEGF, which persisted up to 3 hours post infusion (age effect p=0.04, treatment x time p<0.01). DFO infusion also resulted in a significant time- and age-dependent improvement in cerebral vasoreactivity (treatment x time, p<0.01, age p<0.01) and cerebral autoregulation (gain: age x time x treatment p=0.04). Conclusions DFO infusion improved cerebrovascular function, particularly in older individuals. The temporal association between improved cerebrovascular function and increased serum VEGF and EPO concentrations is supportive of shared HIF-1 regulated pathways. Therefore, pharmacological activation of HIF-1 to enhance cerebrovascular function may be a promising neuroprotective strategy in acute and chronic ischemic syndromes, especially in elderly patients. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT013655104.

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The clinical manifestations and pathophysiology of cerebral small vessel disease

Cited by 33 publications

References 57 publications

Influence of membrane cholesterol and substrate elasticity on endothelial cell spreading behavior

Influence of membrane cholesterol and substrate elasticity on endothelial cell spreading behavior

Experimental animal models and inflammatory cellular changes in cerebral ischemic and hemorrhagic stroke

Deferoxamine, Cerebrovascular Hemodynamics, and Vascular Aging

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