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Sample records for cerebral vascular diseases

  1. Retinal Vascular Changes are a Marker for Cerebral Vascular Diseases.

    PubMed

    Moss, Heather E

    2015-07-01

    The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross-sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease, and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion, and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk.

  2. Pathogenesis of diabetic cerebral vascular disease complication

    PubMed Central

    Xu, Ren-Shi

    2015-01-01

    Diabetes mellitus is one of the most potent independent risk factors for the development of diabetic cerebral vascular disease (CVD). Many evidences suggested that hyperglycemia caused excess free fatty acids, the loss of endothelium-derived nitric oxide, insulin resistance, the prothrombotic state, endothelial dysfunction, the abnormal release of endothelial vasoactivators, vascular smooth muscle dysfunction, oxidative stress, and the downregulation of miRs participated in vessel generation and recovery as well as the balance of endotheliocytes. In turn, these abnormalities, mainly via phosphatidylinositol 3 kinase, mitogen-activated protein kinase, polyol, hexosamine, protein kinase C activation, and increased generation of advanced glycosylation end products pathway, play an important role in inducing diabetic CVD complication. A deeper comprehension of pathogenesis producing diabetic CVD could offer base for developing new therapeutic ways preventing diabetic CVD complications, therefore, in the paper we mainly reviewed present information about the possible pathogenesis of diabetic CVD complication. PMID:25685278

  3. Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke.

    PubMed

    Hu, Xiaoming; De Silva, T Michael; Chen, Jun; Faraci, Frank M

    2017-02-03

    The consequences of cerebrovascular disease are among the leading health issues worldwide. Large and small cerebral vessel disease can trigger stroke and contribute to the vascular component of other forms of neurological dysfunction and degeneration. Both forms of vascular disease are driven by diverse risk factors, with hypertension as the leading contributor. Despite the importance of neurovascular disease and subsequent injury after ischemic events, fundamental knowledge in these areas lag behind our current understanding of neuroprotection and vascular biology in general. The goal of this review is to address select key structural and functional changes in the vasculature that promote hypoperfusion and ischemia, while also affecting the extent of injury and effectiveness of therapy. In addition, as damage to the blood-brain barrier is one of the major consequences of ischemia, we discuss cellular and molecular mechanisms underlying ischemia-induced changes in blood-brain barrier integrity and function, including alterations in endothelial cells and the contribution of pericytes, immune cells, and matrix metalloproteinases. Identification of cell types, pathways, and molecules that control vascular changes before and after ischemia may result in novel approaches to slow the progression of cerebrovascular disease and lessen both the frequency and impact of ischemic events.

  4. Minocycline reduces microgliosis and improves subcortical white matter function in a model of cerebral vascular disease.

    PubMed

    Manso, Yasmina; Holland, Philip R; Kitamura, Akihiro; Szymkowiak, Stefan; Duncombe, Jessica; Hennessy, Edel; Searcy, James L; Marangoni, Martina; Randall, Andrew D; Brown, Jon T; McColl, Barry W; Horsburgh, Karen

    2017-07-19

    Chronic cerebral hypoperfusion is a key mechanism associated with white matter disruption in cerebral vascular disease and dementia. In a mouse model relevant to studying cerebral vascular disease, we have previously shown that cerebral hypoperfusion disrupts axon-glial integrity and the distribution of key paranodal and internodal proteins in subcortical myelinated axons. This disruption of myelinated axons is accompanied by increased microglia and cognitive decline. The aim of the present study was to investigate whether hypoperfusion impairs the functional integrity of white matter, its relation with axon-glial integrity and microglial number, and whether by targeting microglia these effects can be improved. We show that in response to increasing durations of hypoperfusion, the conduction velocity of myelinated fibres in the corpus callosum is progressively reduced and that paranodal and internodal axon-glial integrity is disrupted. The number of microglial cells increases in response to hypoperfusion and correlates with disrupted paranodal and internodal integrity and reduced conduction velocities. Further minocycline, a proposed anti-inflammatory and microglia inhibitor, restores white matter function related to a reduction in the number of microglia. The study suggests that microglial activation contributes to the structural and functional alterations of myelinated axons induced by cerebral hypoperfusion and that dampening microglia numbers/proliferation should be further investigated as potential therapeutic benefit in cerebral vascular disease. © 2017 The Authors GLIA Published by Wiley Periodicals, Inc.

  5. Neuropsychological assessment and cerebral vascular disease: the new standards.

    PubMed

    Godefroy, O; Leclercq, C; Bugnicourt, J-M; Roussel, M; Moroni, C; Quaglino, V; Beaunieux, H; Taillia, H; Nédélec-Ciceri, C; Bonnin, C; Thomas-Anterion, C; Varvat, J; Aboulafia-Brakha, T; Assal, F

    2013-10-01

    Vascular cognitive impairment (VCI) includes vascular dementia (VaD), vascular mild cognitive impairment (VaMCI) and mixed dementia. In clinical practice, VCI concerns patients referred for clinical stroke or cognitive complaint. To improve the characterization of VCI and to refine its diagnostic criteria, an international group has elaborated a new standardized evaluation battery of clinical, cognitive, behavioral and neuroradiological data which now constitutes the reference battery. The adaption of the battery for French-speaking subjects is reported as well as preliminary results of the on-going validation study of the GRECOG-VASC group [Clinical Trial NCT01339195]. The diagnostic accuracy of various screening tests is reviewed and showed an overall sub-optimal sensitivity (<0.8). Thus, the general recommendation is to perform systematically a comprehensive assessment in stroke patients at risk of VCI. Furthermore,the use of a structured interview has been shown to increase the detection of dementia. In addition to the well known NINDS-AIREN criteria of VaD, criteria of VCI have been recently proposed which are based on the demonstration of a cognitive disorder by neuropsychological testing and either history of clinical stroke or presence of vascular lesion by neuroimaging suggestive of a link between cognitive impairment and vascular disease. A memory deficit is no longer required for the diagnosis of VaD as it is based on the cognitive decline concerning two or more domains that affect activities of daily living. Both VaMCI and VaD are classified as probable or possible. These new criteria have yet to be validated. Considerable uncertainties remain regarding the determinant of VCI, and especially the lesion amount inducing VCI and VaD. The interaction between lesion amount and its location is currently re-examined using recent techniques for the analysis of MRI data. The high frequency of associated Alzheimer pathology is now assessable in vivo using amyloid

  6. Post-mortem assessment of hypoperfusion of cerebral cortex in Alzheimer's disease and vascular dementia.

    PubMed

    Thomas, Taya; Miners, Scott; Love, Seth

    2015-04-01

    Perfusion is reduced in the cerebral neocortex in Alzheimer's disease. We have explored some of the mechanisms, by measurement of perfusion-sensitive and disease-related proteins in post-mortem tissue from Alzheimer's disease, vascular dementia and age-matched control brains. To distinguish physiological from pathological reduction in perfusion (i.e. reduction exceeding the decline in metabolic demand), we measured the concentration of vascular endothelial growth factor (VEGF), a protein induced under conditions of tissue hypoxia through the actions of hypoxia-inducible factors, and the myelin associated glycoprotein to proteolipid protein 1 (MAG:PLP1) ratio, which declines in chronically hypoperfused brain tissue. To evaluate possible mechanisms of hypoperfusion, we also measured the levels of amyloid-β40, amyloid-β42, von Willebrand factor (VWF; a measure of microvascular density) and the potent vasoconstrictor endothelin 1 (EDN1); we assayed the activity of angiotensin I converting enzyme (ACE), which catalyses the production of another potent vasoconstrictor, angiotensin II; and we scored the severity of arteriolosclerotic small vessel disease and cerebral amyloid angiopathy, and determined the Braak tangle stage. VEGF was markedly increased in frontal and parahippocampal cortex in Alzheimer's disease but only slightly and not significantly in vascular dementia. In frontal cortex the MAG:PLP1 ratio was significantly reduced in Alzheimer's disease and even more so in vascular dementia. VEGF but not MAG:PLP1 increased with Alzheimer's disease severity, as measured by Braak tangle stage, and correlated with amyloid-β42 and amyloid-β42: amyloid-β40 but not amyloid-β40. Although MAG:PLP1 tended to be lowest in cortex from patients with severe small vessel disease or cerebral amyloid angiopathy, neither VEGF nor MAG:PLP1 correlated significantly with the severity of structural vascular pathology (small vessel disease, cerebral amyloid angiopathy or VWF

  7. Cerebral Blood Flow in Ischemic Vascular Dementia and Alzheimer's Disease By Arterial Spin Labeling MRI

    PubMed Central

    Schuff, N.; Matsumoto, S.; Kmiecik, J.; Studholme, C.; Du, A.T.; Ezekiel, F.; Miller, B.L.; Kramer, J.H.; Jagust, W.J.; Chui, H.C.; Weiner, M.W.

    2009-01-01

    Background The objectives were first to compare the effects of subcortical ischemic vascular dementia (SIVD) and Alzheimer's disease (AD) on cerebral blood flow (CBF) and second to analyze the relationship between CBF and subcortical vascular disease, measured as volume of white matter lesions (WML). Methods Eight mildly demented patients with SIVD (77 ± 8 years, 26 ± 3 MMSE) and 14 patients with AD were compared to 18 cognitively normal elderly. All subjects had CBF measured using arterial spin labeling MRI and brain volumes assessed using structural MRI. Results AD and SIVD showed marked CBF reductions in frontal (p = 0.001) and parietal (p = 0.001) cortex. In SIVD, increased subcortical WML were associated with reduced CBF in frontal cortex (p = 0.04) in addition to cortical atrophy (frontal: p = 0.05; parietal: p = 0.03). Conclusions Subcortical vascular disease is associated with reduced CBF in the cortex, irrespective of brain atrophy. PMID:19896584

  8. Modeling Cerebral Vascular Injury

    DTIC Science & Technology

    2016-01-01

    Using a pressure gradient to drive the blood flow, and the external pressure induced by a blast wave through the surrounding brain elements, an...unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT Many numerical models for the brain do not include the vascular structures within the brain and thus...are incapable of predicting damage to the cerebral vasculature. The presence of the vasculature within the brain produces a reinforcing effect and

  9. Low Cerebral Glucose Metabolism: A Potential Predictor for the Severity of Vascular Parkinsonism and Parkinson's Disease.

    PubMed

    Xu, Yunqi; Wei, Xiaobo; Liu, Xu; Liao, Jinchi; Lin, Jiaping; Zhu, Cansheng; Meng, Xiaochun; Xie, Dongsi; Chao, Dongman; Fenoy, Albert J; Cheng, Muhua; Tang, Beisha; Zhang, Zhuohua; Xia, Ying; Wang, Qing

    2015-11-01

    This study explored the association between cerebral metabolic rates of glucose (CMRGlc) and the severity of Vascular Parkinsonism (VP) and Parkinson's disease (PD). A cross-sectional study was performed to compare CMRGlc in normal subjects vs. VP and PD patients. Twelve normal subjects, 22 VP, and 11 PD patients were evaluated with the H&Y and MMSE, and underwent 18F-FDG measurements. Pearson's correlations were used to identify potential associations between the severity of VP/PD and CMRGlc. A pronounced reduction of CMRGlc in the frontal lobe and caudate putamen was detected in patients with VP and PD when compared with normal subjects. The VP patients displayed a slight CMRGlc decrease in the caudate putamen and frontal lobe in comparison with PD patients. These decreases in CMRGlc in the frontal lobe and caudate putamen were significantly correlated with the VP patients' H&Y, UPDRS II, UPDRS III, MMSE, cardiovascular, and attention/memory scores. Similarly, significant correlations were observed in patients with PD. This is the first clinical study finding strong evidence for an association between low cerebral glucose metabolism and the severity of VP and PD. Our findings suggest that these changes in glucose metabolism in the frontal lobe and caudate putamen may underlie the pathophysiological mechanisms of VP and PD. As the scramble to find imaging biomarkers or predictors of the disease intensifies, a better understanding of the roles of cerebral glucose metabolism may give us insight into the pathogenesis of VP and PD.

  10. [Clinical analysis of 7 patients with Gerstmann syndrome secondary to cerebral vascular disease].

    PubMed

    Zhou, Xiang-qin; He, Rui; Liu, Zhi; Wang, Chang-qing

    2002-10-01

    To analyze clinical features of patients with Gerstmann syndrome (GS). We retrospectively analysed the clinical manifestations of 7 patients (6 men and 1 woman) with GS secondary to cerebral vascular diseases and reviewed the literatures. The age ranged from 51 to 70 years with a mean of 70 years. They all had sudden onset and the tetrad of GS-finger agnosia, left-right disorientation, agraphia and acalculia, 3 patients accompanied by incomplete aphasia, 3 by anomic aphasia, 2 by alexia and 1 by constructional apraxia. Cranial computed tomographic scan showed low-density focus of the left parietal lobe in 6 cases and high-density focus of the left parietal lobe in 1 case. GS has the high value in localization and the lesion is mainly localized to angular gyrus of the dominant hemisphere.

  11. Cerebral cavernous malformations as a disease of vascular permeability: from bench to bedside with caution.

    PubMed

    Yadla, Sanjay; Jabbour, Pascal M; Shenkar, Robert; Shi, Changbin; Campbell, Peter G; Awad, Issam A

    2010-09-01

    Tremendous insight into the molecular and genetic pathogenesis of cerebral cavernous malformations (CCMs) has been gained over the past 2 decades. This includes the identification of 3 distinct genes involved in familial CCMs. Still, a number of unanswered questions regarding the process from gene mutation to vascular malformation remain. It is becoming more evident that the disruption of interendothelial junctions and ensuing vascular hyperpermeability play a principal role. The purpose of this review is to summarize the current understanding of CCM genes, associated proteins, and functional pathways. Promising molecular and genetic therapies targeted at identified molecular aberrations are discussed as well.

  12. What Is Vascular Disease?

    MedlinePlus

    ... Donors Corporate Sponsors Donor Privacy Policy What Is Vascular Disease? What Is Vascular Disease? Vascular disease is any abnormal condition of ... steps to prevent vascular disease here. Understanding the Vascular System Your vascular system – the highways of the ...

  13. Hydrogen peroxide induces apoptosis in cerebral vascular smooth muscle cells: possible relation to neurodegenerative diseases and strokes.

    PubMed

    Li, Jianfeng; Li, Wenyan; Su, Jialin; Liu, Weimin; Altura, Bella T; Altura, Burton M

    2003-12-15

    Recently, reactive oxygen species (ROS) have been suggested as important mediators of brain damage in a number of disease states, including traumatic brain injury, neurodegenerative diseases and strokes. Apoptosis has been suggested to play an important role in neurodegenerative diseases, traumatic brain injury and strokes. The aim of this study was to determine whether or not cerebral vascular smooth muscle cells (CVSMCs) undergo apoptosis following treatment with hydrogen peroxide (H2O2). Herein, we demonstrate, for the first time, that H2O2 can induce apoptosis in a concentration-dependent manner in primary cultured CVSMCs, as measured by several morphological and biochemical criteria. H2O2-induced apoptosis may be initiated by stimulating Ca2+-dependent endonuclease activity. The present new data suggest that apoptosis in cerebral VSMCs, induced by ROS, such as H2O2, could play important roles in neruodegenerative processes, traumatic brain injury and strokes.

  14. Associations of ankle-brachial index (ABI) with cerebral arterial disease and vascular events following ischemic stroke.

    PubMed

    Manzano, Jennifer Justice F; De Silva, Deidre A; Pascual, Jose Leonard R; Chang, Hui-Meng; Wong, Meng-Cheong; Chen, Christopher P L H

    2012-07-01

    Low ankle-brachial index (ABI), indicative of peripheral arterial disease (PAD), is a risk factor for stroke. ABI has been shown to be associated with cerebral arterial disease and prognosis following stroke. We studied the associations of the degree of ABI lowering with extracranial carotid disease (ECD), intracranial large artery disease (ICLAD), and subsequent vascular events in a prospective cohort of acute ischemic stroke patients. ABI, extracranial and intracranial cerebral arteries were assessed in a blinded manner. ABI was categorized into 0.9-1.3 (normal), 0.8-0.89 (mildly lowered) and <0.8 (severely lowered). Follow-up data at 1 year were obtained from standardized telephone interviews and verified with medical records. Among the 1311 patients, 73% had normal ABI, 13% had ABI 0.8-0.89 and 13% had ABI <0.8. Compared to patients with normal ABI, those with ABI<0.8 had higher prevalence of severe ECD (15% vs. 5%, p = 0.006) and ICLAD (72% vs. 48%, p = 0.003), even after adjustment for age, gender, hypertension, diabetes, hyperlipidemia, smoking, ischemic heart disease and atrial fibrillation (severe ECD p < 0.001, ICLAD p < 0.001). At 1 year, patients with ABI <0.8 had a higher incidence of composite vascular events (19% vs. 11%, p = 0.02), stroke (15% vs. 10%, p = 0.06) and myocardial infarction (4% vs. 2%, p = 0.07) than patients with normal ABI. Among ischemic stroke patients, large cerebral arterial disease and incidence of subsequent vascular events at 1 year were associated with severe ABI lowering <0.8, but not with mild ABI lowering (0.8-0.89). Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. What Is Vascular Disease?

    MedlinePlus

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  16. Vascular Disease Foundation

    MedlinePlus

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  17. Peroxynitrite induces apoptosis in canine cerebral vascular muscle cells: possible relation to neurodegenerative diseases and strokes.

    PubMed

    Li, Jianfeng; Su, Jialin; Li, Wenyan; Liu, Weimin; Altura, Bella T; Altura, Burton M

    2003-10-30

    Considerable evidence is accumulating to suggest that in vivo formation of free radicals in the brain, such as peroxynitrite (ONOO-), and programmed cell death (i.e. apoptosis) play important roles in neurodegeneration and stroke. However, it is not known whether ONOO- can induce apoptosis in cerebral vascular smooth muscle cells (CVSMCs). The present study was designed to determine whether or not canine CVSMCs undergo apoptosis following treatment with ONOO-. Direct exposure of canine CVSMCs to ONOO- induced apoptosis in a concentration-dependent manner, as confirmed by means of fluorescence staining, TdT-mediated dUTP nick-end labeling and comet assays. Peroxynitrite treatment resulted in an elevation of [Ca2+]i in the CVSMCs. Peroxynitrite-induced apoptosis may thus be brought about by activation of Ca2+-dependent endonucleases. Although the precise mechanisms by which peroxynitrite induces apoptosis need to be further investigated, the present findings could be used to suggest that ONOO- formation in the brain may play important roles in neurodegenerative processes and strokes via detrimental actions on cerebral microvessels and blood flow.

  18. [Diabetes mellitus and aging as a risk factor for cerebral vascular disease: epidemiology, pathophysiology and prevention].

    PubMed

    Cantú-Brito, Carlos; Mimenza-Alvarado, Alberto; Sánchez-Hernández, Juan José

    2010-01-01

    Older patients with diabetes have a high risk of vascular complications. They have an increase of approximately 3 times for developing stroke compared with subjects without diabetes. In addition, up to 75-80% of deaths in diabetic patients are associated with major cardiovascular events including stroke. The risk of stroke is high within 5 years of diagnosis for type 2 diabetes is 9% (mortality 21%), that is more than doubles the rate for the general population. From observational registries in a collaborative stroke study in Mexico, we analyzed clinical data, risk factors, and outcome of 1182 diabetic patients with cerebral ischemia, with focus in elderly subjects. There was a high frequency of hyperglycemia during the acute phase of stroke: the median value was 140 mg/dL and 40% had values higher than 180 mg/dL. Clinical outcome was usually unfavorable in elderly stroke patients with diabetes: case fatality rate was 30% at 30 days and survivors had moderate to severe disability, usually as consequence of the propensity to develop more systemic medical complications during hospital stay. Primary stroke prevention studies in patients with diabetes reveal that tight control of glucose is not associated with reduction in stroke risk. Therefore, proper control of other vascular risk factors is mandatory in patients with diabetes, in particular of arterial hypertension.

  19. beta-amyloid protein of Alzheimer's disease is found in cerebral and spinal cord vascular malformations.

    PubMed Central

    Hart, M. N.; Merz, P.; Bennett-Gray, J.; Menezes, A. H.; Goeken, J. A.; Schelper, R. L.; Wisniewski, H. M.

    1988-01-01

    Congo/Red deposition with birefringence to polarized light was demonstrated focally in cerebrovascular malformations removed surgically from 4 older patients (ages 85, 74, 74, and 63), and in a spinal cord vascular malformation in a 76-year-old patient. Lesser degrees of Congophilic change were observed in cerebrovascular malformations screened from 4 of 10 patients between the ages of 30 and 59. No Congophilic change was seen in 10 cerebrovascular malformations removed from patients under 30 years of age. Congophilic areas in all cases decorated with W-2 and 85/45 polyclonal antibodies raised to peptide sequences of cerebrovascular beta-amyloid and beta-amyloid of senile plaques from patients with Alzheimer's disease. Thus, the amyloid in these vascular malformations is immunologically related to beta-amyloid protein. This finding provides another indication that vascular beta-amyloid deposition is not specific for Alzheimer's disease and suggests that an existing abnormality of vessels may be a predisposing factor. Images Figure 1 Figure 2A Figure 2B Figure 3 Figure 4 PMID:3293463

  20. Regional cerebral blood flow and cerebrovascular reactivity in Alzheimer's disease and vascular dementia assessed by arterial spinlabeling magnetic resonance imaging.

    PubMed

    Gao, Yong-Zhe; Zhang, Jun-Jian; Liu, Hui; Wu, Guang-Yao; Xiong, Li; Shu, Min

    2013-02-01

    Hemodynamic disturbance in cerebral blood flow (CBF) is common in both Alzheimer's disease (AD) and vascular dementia (VaD).The aim of this study is to investigate the different patterns of regional cerebral blood flow (rCBF) change and cerebrovascular reactivity (CVR) in these two types of dementia. Mean flow velocity (MFV) of middle cerebral artery and rCBF were measured by Transcranial Doppler ultrasound (TCD) and arterial spin-labeling (ASL) magnetic resonance, separately. CVR was evaluated by MFV or rCBF change in response to 5% CO2 inhalation. The ASL results showed that, rCBF was significantly lower in both the bilateral frontal and temporal lobes in AD group and lower in left frontal and temporal white matter in patients with VaD. CVR calculated by rCBF was impaired more severely in bilateral frontal cortices in AD. Conversely, TCD tests failed to demonstrate significant difference in MFV and CVR between the two groups. It is concluded that the different patterns detected by ASL in resting rCBF change and cerebrovascular reactivity in response to carbogen inhalation may serve as a potential marker to distinguish AD and VaD.

  1. Vascular Diseases

    MedlinePlus

    The vascular system is the body's network of blood vessels. It includes the arteries, veins and capillaries that carry ... to and from the heart. Problems of the vascular system are common and can be serious. Arteries ...

  2. Low Cerebral Glucose Metabolism: A Potential Predictor for the Severity of Vascular Parkinsonism and Parkinson’s Disease

    PubMed Central

    Xu, Yunqi; Wei, Xiaobo; Liu, Xu; Liao, Jinchi; Lin, Jiaping; Zhu, Cansheng; Meng, Xiaochun; Xie, Dongsi; Chao, Dongman; Fenoy, Albert J; Cheng, Muhua; Tang, Beisha; Zhang, Zhuohua; Xia, Ying; Wang, Qing

    2015-01-01

    This study explored the association between cerebral metabolic rates of glucose (CMRGlc) and the severity of Vascular Parkinsonism (VP) and Parkinson’s disease (PD). A cross-sectional study was performed to compare CMRGlc in normal subjects vs. VP and PD patients. Twelve normal subjects, 22 VP, and 11 PD patients were evaluated with the H&Y and MMSE, and underwent 18F-FDG measurements. Pearson’s correlations were used to identify potential associations between the severity of VP/PD and CMRGlc. A pronounced reduction of CMRGlc in the frontal lobe and caudate putamen was detected in patients with VP and PD when compared with normal subjects. The VP patients displayed a slight CMRGlc decrease in the caudate putamen and frontal lobe in comparison with PD patients. These decreases in CMRGlc in the frontal lobe and caudate putamen were significantly correlated with the VP patients’ H&Y, UPDRS II, UPDRS III, MMSE, cardiovascular, and attention/memory scores. Similarly, significant correlations were observed in patients with PD. This is the first clinical study finding strong evidence for an association between low cerebral glucose metabolism and the severity of VP and PD. Our findings suggest that these changes in glucose metabolism in the frontal lobe and caudate putamen may underlie the pathophysiological mechanisms of VP and PD. As the scramble to find imaging biomarkers or predictors of the disease intensifies, a better understanding of the roles of cerebral glucose metabolism may give us insight into the pathogenesis of VP and PD. PMID:26618044

  3. Cerebral vascular abnormalities in pediatric patients with sickle cell disease after hematopoietic cell transplant.

    PubMed

    Bodas, Prasad; Rotz, Seth

    2014-04-01

    Stroke is a common sequela of sickle cell disease (SCD). Patients with SCD who undergo hematopoietic stem cell transplantation (HSCT) with successful engraftment will not experience sickling. This ameliorates one aspect of stroke risk; however, the significance of preexisting cerebrovascular abnormalities remains unclear. We performed a literature search for neurological outcomes following HSCT for SCD. We searched for relevant neuroimaging and neurosurgical protocols. We identified 4 unique studies encompassing 196 patients. Of these, 81 had a history of a stroke, transient ischemic attack (TIA), cognitive dysfunction or cerebrovascular abnormalities identified by pretransplant neuroimaging, achieved stable engraftment, and had long-term follow-up. Of the 81 patients, 1 had peritransplant (10 days prior transplant to 50 days posttransplant) TIA. One had posttransplant TIA within 36 to 72 months. None had strokes. Forty-five underwent cerebral imaging at nonuniform intervals. Among this group, 32 (71%) had stable cerebrovascular abnormalities on imaging, 6 (13%) had improvement, and 7 (16%) showed worsening. Cerebrovascular abnormalities identified on neuroimaging may stabilize, improve, or worsen in patients after successful HSCT. Some patients may have neurological events such as TIA. Neurological outcomes in children with SCD post-HSCT have been inadequately studied.

  4. Vascular and parenchymal amyloid pathology in an Alzheimer disease knock-in mouse model: interplay with cerebral blood flow

    PubMed Central

    2014-01-01

    Background Accumulation and deposition of β-amyloid peptides (Aβ) in the brain is a central event in the pathogenesis of Alzheimer’s disease (AD). Besides the parenchymal pathology, Aβ is known to undergo active transport across the blood–brain barrier and cerebral amyloid angiopathy (CAA) is a prominent feature in the majority of AD. Although impaired cerebral blood flow (CBF) has been implicated in faulty Aβ transport and clearance, and cerebral hypoperfusion can exist in the pre-clinical phase of Alzheimer’s disease (AD), it is still unclear whether it is one of the causal factors for AD pathogenesis, or an early consequence of a multi-factor condition that would lead to AD at late stage. To study the potential interaction between faulty CBF and amyloid accumulation in clinical-relevant situation, we generated a new amyloid precursor protein (APP) knock-in allele that expresses humanized Aβ and a Dutch mutation in addition to Swedish/London mutations and compared this line with an equivalent knock-in line but in the absence of the Dutch mutation, both crossed onto the PS1M146V knock-in background. Results Introduction of the Dutch mutation results in robust CAA and parenchymal Aβ pathology, age-dependent reduction of spatial learning and memory deficits, and CBF reduction as detected by fMRI. Direct manipulation of CBF by transverse aortic constriction surgery on the left common carotid artery caused differential changes in CBF in the anterior and middle region of the cortex, where it is reduced on the left side and increased on the right side. However these perturbations in CBF resulted in the same effect: both significantly exacerbate CAA and amyloid pathology. Conclusions Our study reveals a direct and positive link between vascular and parenchymal Aβ; both can be modulated by CBF. The new APP knock-in mouse model recapitulates many symptoms of AD including progressive vascular and parenchymal Aβ pathology and behavioral deficits in the absence

  5. Vascular permeability in cerebral cavernous malformations

    PubMed Central

    Mikati, Abdul G; Khanna, Omaditya; Zhang, Lingjiao; Girard, Romuald; Shenkar, Robert; Guo, Xiaodong; Shah, Akash; Larsson, Henrik BW; Tan, Huan; Li, Luying; Wishnoff, Matthew S; Shi, Changbin; Christoforidis, Gregory A; Awad, Issam A

    2015-01-01

    Patients with the familial form of cerebral cavernous malformations (CCMs) are haploinsufficient for the CCM1, CCM2, or CCM3 gene. Loss of corresponding CCM proteins increases RhoA kinase-mediated endothelial permeability in vitro, and in mouse brains in vivo. A prospective case-controlled observational study investigated whether the brains of human subjects with familial CCM show vascular hyperpermeability by dynamic contrast-enhanced quantitative perfusion magnetic resonance imaging, in comparison with CCM cases without familial disease, and whether lesional or brain vascular permeability correlates with CCM disease activity. Permeability in white matter far (WMF) from lesions was significantly greater in familial than in sporadic cases, but was similar in CCM lesions. Permeability in WMF increased with age in sporadic patients, but not in familial cases. Patients with more aggressive familial CCM disease had greater WMF permeability compared to those with milder disease phenotype, but similar lesion permeability. Subjects receiving statin medications for routine cardiovascular indications had a trend of lower WMF, but not lesion, permeability. This is the first demonstration of brain vascular hyperpermeability in humans with an autosomal dominant disease, as predicted mechanistically. Brain permeability, more than lesion permeability, may serve as a biomarker of CCM disease activity, and help calibrate potential drug therapy. PMID:25966944

  6. Vascular permeability in cerebral cavernous malformations.

    PubMed

    Mikati, Abdul G; Khanna, Omaditya; Zhang, Lingjiao; Girard, Romuald; Shenkar, Robert; Guo, Xiaodong; Shah, Akash; Larsson, Henrik B W; Tan, Huan; Li, Luying; Wishnoff, Matthew S; Shi, Changbin; Christoforidis, Gregory A; Awad, Issam A

    2015-10-01

    Patients with the familial form of cerebral cavernous malformations (CCMs) are haploinsufficient for the CCM1, CCM2, or CCM3 gene. Loss of corresponding CCM proteins increases RhoA kinase-mediated endothelial permeability in vitro, and in mouse brains in vivo. A prospective case-controlled observational study investigated whether the brains of human subjects with familial CCM show vascular hyperpermeability by dynamic contrast-enhanced quantitative perfusion magnetic resonance imaging, in comparison with CCM cases without familial disease, and whether lesional or brain vascular permeability correlates with CCM disease activity. Permeability in white matter far (WMF) from lesions was significantly greater in familial than in sporadic cases, but was similar in CCM lesions. Permeability in WMF increased with age in sporadic patients, but not in familial cases. Patients with more aggressive familial CCM disease had greater WMF permeability compared to those with milder disease phenotype, but similar lesion permeability. Subjects receiving statin medications for routine cardiovascular indications had a trend of lower WMF, but not lesion, permeability. This is the first demonstration of brain vascular hyperpermeability in humans with an autosomal dominant disease, as predicted mechanistically. Brain permeability, more than lesion permeability, may serve as a biomarker of CCM disease activity, and help calibrate potential drug therapy.

  7. Luxury perfusion syndrome in cerebral vascular disease evaluated with technetium-99m HM-PAO.

    PubMed

    Spreafico, G; Cammelli, F; Gadola, G; Freschi, R; Zancaner, F

    1987-03-01

    A recently developed Tc-99m radiocompound, hexamethylpropyleneamine oxime (Tc-99m HM-PAO), exhibits favorable properties for regional cerebral blood flow study in man. The authors present a case of luxury perfusion syndrome observed in a 72-year-old patient with acute stroke and a right-sided hemiplegia, documented by planar scintigraphy and SPECT study in correlation with CT scan. The metabolic basis of this phenomenon is discussed and the usefulness of assessing regional brain perfusion by Tc-99m HM-PAO with conventional nuclear medicine equipment is underlined.

  8. Vascular pathology in Alzheimer disease: correlation of cerebral amyloid angiopathy and arteriosclerosis/lipohyalinosis with cognitive decline.

    PubMed

    Thal, Dietmar Rudolf; Ghebremedhin, Estifanos; Orantes, Mario; Wiestler, Otmar D

    2003-12-01

    Sporadic, late-onset Alzheimer disease (AD) constitutes the most frequent cause of dementia in the elderly population. AD-related pathology is often accompanied by vascular changes. The predominant vascular lesions in AD are cerebral amyloid angiopathy (CAA) and arteriosclerosis/lipohyalinosis (AS/LH). The present study was carried out to examine the coincidence of these small vessel pathologies during the development of cognitive deficits, amyloid beta-protein (A beta) deposition, and neurofibrillary tangle (NFT) formation in sporadic late-onset AD. We correlated the clinical dementia rating (CDR) score, the sequential extension of AD-related A beta deposition into different parts of the brain, and the extension of NFTs to involve more brain regions with the distribution of CAA and AS/LH in 52 human autopsy brains. The extension of CAA and AS/LH to involve different areas of the brain was associated with a rise of CDR scores and an increase in the extension of A beta deposition and NFT generation. AD cases showed a higher number of regions with CAA and AS/LH compared to nondemented patients with AD-related pathology and controls. Moreover, we demonstrated a hierarchical sequence in which the different regions of the brain exhibited CAA and AS/LH-affected vessels, allowing the distinction of 3 stages in the development of CAA and AS/LH. The first stage of CAA involved leptomeningeal and neocortical vessels. The second stage was characterized by additional A beta deposition in allocortical and midbrain vessels. Finally, in a third stage, CAA was observed in the basal ganglia, the thalamus, and in the lower brainstem. In contrast, AS/LH initially affected the basal ganglia in stage A. In stage B this pathology made inroads into the deep white matter, the leptomeningeal arteries of the cortex, the cerebellum, and into the thalamus. Stage C was characterized by AS/LH in brainstem vessels. Our results demonstrate widespread CAA and AS/LH to be associated with the

  9. P66(Shc)-SIRT1 Regulation of Oxidative Stress Protects Against Cardio-cerebral Vascular Disease.

    PubMed

    Kong, Xiangyi; Guan, Jian; Li, Jun; Wei, Junji; Wang, Renzhi

    2017-09-01

    Growing evidence shows that acute and chronic overproduction of reactive oxygen species (ROS) and increased oxidants under pathophysiologic circumstances are of vital importance in the development of cardio-cerebral vascular diseases (CCVDs). It has been revealed that the impact of ROS can be suppressed by sirtuin 1 (SIRT1), a member of the highly conserved nicotinamide adenine dinucleotide-dependent class III histone deacetylases through protecting endothelial cells from oxidative injury. Plenty of evidences indicate that p66Shc stimulates mitochondrial ROS generation through its oxidoreductase activity and plays a vital role in the pathophysiology of CCVDs. The link between SIRT and p66Shc, though not very clear yet, may be generally illustrated like this: SIRT1 negatively regulates the expression of p66Shc in transcriptional level. In this review, the authors aimed to discuss the link between the pathogenesis of CCVDs, the regulation of ROS, the interrelation between SIRT1 and p66Shc, and the protective effect of the proper regulation of p66Shc/SIRT1 on CCVDs. The imbalance between the elimination and production of ROS can lead to oxidative stress (OS). More and more evidence suggest that ROS pathological overproduction is closely connected to the genesis and growth of CCVDs. P66shc is a gene that controls ROS level, apoptosis induction, and lifespan. Lots of evidence also indicate a role for SIRT1 mediating OS responses through several ways including directly deacetylating some transcription factors that control anti-OS genes. SIRT1 downregulation can lead to a decreased deacetylation of p66shc gene promoter and can then result in p66shc transcription. SIRT1 binds to the promoter of p66Shc where it can deacetylate histone H3, which weakens the transcription and translation of p66shc.

  10. Acute cerebral vascular accident associated with hyperperfusion.

    PubMed

    Soin, J S; Burdine, J A

    1976-01-01

    Cerebral radionuclide angiography can demonstrate decreased or normal radioactivity in the affected region during the arterial phase in patients who have sustained a cerebral vascular accident and thus enhances the diagnostic specificity of the static brain image. In an occasional patient, however, a seemingly paradoxical pattern of regional hyperperfusion with a return to normal or subnormal perfusion following the acute phase has been observed. This phenomenon, called "luxury perfusion," has been defined using intra-arterial 133Xe for semiquantitative cerebral blood flow measurements and should be kept in mind as a potentially misleading cerebral imaging pattern.

  11. The leptomeningeal "ivy sign" on fluid-attenuated inversion recovery MR imaging in Moyamoya disease: a sign of decreased cerebral vascular reserve?

    PubMed

    Mori, N; Mugikura, S; Higano, S; Kaneta, T; Fujimura, M; Umetsu, A; Murata, T; Takahashi, S

    2009-05-01

    Moyamoya disease is an idiopathic occlusive cerebrovascular disorder with abnormal microvascular proliferation. We investigated the clinical utility of leptomeningeal high signal intensity (ivy sign) sometimes seen on fluid-attenuated inversion recovery images in Moyamoya disease. We examined the relationship between the degree of the ivy sign and the severity of the ischemic symptoms in 96 hemispheres of 48 patients with Moyamoya disease. We classified each cerebral hemisphere into 4 regions from anterior to posterior. In 192 regions of 24 patients, we examined the relationship between the degree of the ivy sign and findings of single-photon emission CT, including the resting cerebral blood flow (CBF) and cerebral vascular reserve (CVR). The degree of the ivy sign showed a significant positive relationship with the severity of the ischemic symptoms (P < .001). Of the 4 regions, the ivy sign was most frequently and prominently seen in the anterior part of the middle cerebral artery region. The degree of the ivy sign showed a negative relationship with the resting CBF (P < .0034) and a more prominent negative relationship with the CVR (P < .001). The leptomeningeal ivy sign indicates decreased CVR in Moyamoya disease.

  12. [The blood glutathione system in cerebral vascular diseases and its treatment with alpha-lipoic acid].

    PubMed

    Kolesnichenko, L S; Kulinskiĭ, V I; Shprakh, V V; Bardymov, V V; Verlan, N V; Gubina, L P; Pensionerova, G A; Sergeeva, M P; Stanevich, L M; Filippova, G T

    2008-01-01

    The changes of glutathione metabolism are rare in dyscirculatory encephalopathy and ischemic stroke (IS) of mild severity. The frequent and considerable changes have been revealed in IS of moderate and high severity as well as in hemorrhagic stroke. An increase of activities of glutathione peroxidase and glutathione transferase is the most typical. The increase of enzyme activity was not observed at the beginning of treatment after 3 days and in patients with severe degree of disease who died later. A standard therapy decreased the quantity and/or expression of changes of the glutathione metabolism in patients with IS of moderate and high severity while the addition of alpha-lipoic acid (alpha-LA) led to the complete normalization in IS of moderate severity and normalization of most parameters in IS of high severity. The increase of functional activity of the glutathione system at the early stage of treatment of IS and the favorable changes during the treatment, in particular after the addition of alpha-LA, were correlated with the improvement of neurological status assessed with the NIHSS. It has been confirmed that the glutathione system plays an important role in the tolerance to brain ischemia.

  13. Sleep Apnea, Sleep Duration and Brain MRI Markers of Cerebral Vascular Disease and Alzheimer's Disease: The Atherosclerosis Risk in Communities Study (ARIC).

    PubMed

    Lutsey, Pamela L; Norby, Faye L; Gottesman, Rebecca F; Mosley, Thomas; MacLehose, Richard F; Punjabi, Naresh M; Shahar, Eyal; Jack, Clifford R; Alonso, Alvaro

    2016-01-01

    A growing body of literature has suggested that obstructive sleep apnea (OSA) and habitual short sleep duration are linked to poor cognitive function. Neuroimaging studies may provide insight into this relation. We tested the hypotheses that OSA and habitual short sleep duration, measured at ages 54-73 years, would be associated with adverse brain morphology at ages 67-89 years. Included in this analysis are 312 ARIC study participants who underwent in-home overnight polysomnography in 1996-1998 and brain MRI scans about 15 years later (2012-2013). Sleep apnea was quantified by the apnea-hypopnea index and categorized as moderate/severe (≥15.0 events/hour), mild (5.0-14.9 events/hour), or normal (<5.0 events/hour). Habitual sleep duration was categorized, in hours, as <7, 7 to <8, ≥8. MRI outcomes included number of infarcts (total, subcortical, and cortical) and white matter hyperintensity (WMH) and Alzheimer's disease signature region volumes. Multivariable adjusted logistic and linear regression models were used. All models incorporated inverse probability weighting, to adjust for potential selection bias. At the time of the sleep study participants were 61.7 (SD: 5.0) years old and 54% female; 19% had moderate/severe sleep apnea. MRI imaging took place 14.8 (SD: 1.0) years later, when participants were 76.5 (SD: 5.2) years old. In multivariable models which accounted for body mass index, neither OSA nor abnormal sleep duration were statistically significantly associated with odds of cerebral infarcts, WMH brain volumes or regional brain volumes. In this community-based sample, mid-life OSA and habitually short sleep duration were not associated with later-life cerebral markers of vascular dementia and Alzheimer's disease. However, selection bias may have influenced our results and the modest sample size led to relatively imprecise associations.

  14. Cerebral vascular hamartoma in a geriatric cat

    PubMed Central

    Martin-Vaquero, Paula; Moore, Sarah A; Wolk, Kendra E; Oglesbee, Michael J

    2014-01-01

    An 11-year-old castrated male domestic medium hair cat was presented with neurological signs consistent with a right thalamocortical lesion. Computed tomography (CT) images revealed a heterogeneously, hyperattenuating, poorly contrast enhancing intra-axial mass within the right lateral ventricle. The histological diagnosis at post-mortem examination was vascular hamartoma with hemorrhage and necrosis. This is the first report of a vascular hamartoma affecting the thalamocortex in a geriatric cat. Also, this is the first time that CT images of a feline cerebral vascular hamartoma have been reported. PMID:21277244

  15. The Vascular Depression Hypothesis: Mechanisms Linking Vascular Disease with Depression

    PubMed Central

    Taylor, Warren D.; Aizenstein, Howard J.; Alexopoulos, George S.

    2013-01-01

    The ‘Vascular Depression’ hypothesis posits that cerebrovascular disease may predispose, precipitate, or perpetuate some geriatric depressive syndromes. This hypothesis stimulated much research that has improved our understanding of the complex relationships between late-life depression (LLD), vascular risk factors, and cognition. Succinctly, there are well-established relationships between late-life depression, vascular risk factors, and cerebral hyperintensities, the radiological hallmark of vascular depression. Cognitive dysfunction is common in late-life depression, particularly executive dysfunction, a finding predictive of poor antidepressant response. Over time, progression of hyperintensities and cognitive deficits predicts a poor course of depression and may reflect underlying worsening of vascular disease. This work laid the foundation for examining the mechanisms by which vascular disease influences brain circuits and influences the development and course of depression. We review data testing the vascular depression hypothesis with a focus on identifying potential underlying vascular mechanisms. We propose a disconnection hypothesis, wherein focal vascular damage and white matter lesion location is a crucial factor influencing neural connectivity that contributes to clinical symptomatology. We also propose inflammatory and hypoperfusion hypotheses, concepts that link underlying vascular processes with adverse effects on brain function that influence the development of depression. Testing such hypotheses will not only inform the relationship between vascular disease and depression but also provide guidance on the potential repurposing of pharmacological agents that may improve late-life depression outcomes. PMID:23439482

  16. Astrocyte regulation of cerebral vascular tone

    PubMed Central

    Iddings, Jennifer A.

    2013-01-01

    Cerebral blood flow is controlled by two crucial processes, cerebral autoregulation (CA) and neurovascular coupling (NVC) or functional hyperemia. Whereas CA ensures constant blood flow over a wide range of systemic pressures, NVC ensures rapid spatial and temporal increases in cerebral blood flow in response to neuronal activation. The focus of this review is to discuss the cellular mechanisms by which astrocytes contribute to the regulation of vascular tone in terms of their participation in NVC and, to a lesser extent, CA. We discuss evidence for the various signaling modalities by which astrocytic activation leads to vasodilation and vasoconstriction of parenchymal arterioles. Moreover, we provide a rationale for the contribution of astrocytes to pressure-induced increases in vascular tone via the vasoconstrictor 20-HETE (a downstream metabolite of arachidonic acid). Along these lines, we highlight the importance of the transient receptor potential channel of the vanilloid family (TRPV4) as a key molecular determinant in the regulation of vascular tone in cerebral arterioles. Finally, we discuss current advances in the technical tools available to study NVC mechanisms in the brain as it relates to the participation of astrocytes. PMID:23792684

  17. Cerebral Vascular Injury in Traumatic Brain Injury.

    PubMed

    Kenney, Kimbra; Amyot, Franck; Haber, Margalit; Pronger, Angela; Bogoslovsky, Tanya; Moore, Carol; Diaz-Arrastia, Ramon

    2016-01-01

    Traumatic cerebral vascular injury (TCVI) is a very frequent, if not universal, feature after traumatic brain injury (TBI). It is likely responsible, at least in part, for functional deficits and TBI-related chronic disability. Because there are multiple pharmacologic and non-pharmacologic therapies that promote vascular health, TCVI is an attractive target for therapeutic intervention after TBI. The cerebral microvasculature is a component of the neurovascular unit (NVU) coupling neuronal metabolism with local cerebral blood flow. The NVU participates in the pathogenesis of TBI, either directly from physical trauma or as part of the cascade of secondary injury that occurs after TBI. Pathologically, there is extensive cerebral microvascular injury in humans and experimental animal, identified with either conventional light microscopy or ultrastructural examination. It is seen in acute and chronic TBI, and even described in chronic traumatic encephalopathy (CTE). Non-invasive, physiologic measures of cerebral microvascular function show dysfunction after TBI in humans and experimental animal models of TBI. These include imaging sequences (MRI-ASL), Transcranial Doppler (TCD), and Near InfraRed Spectroscopy (NIRS). Understanding the pathophysiology of TCVI, a relatively under-studied component of TBI, has promise for the development of novel therapies for TBI.

  18. Progressive cerebral occlusive disease after radiation therapy.

    PubMed

    Bitzer, M; Topka, H

    1995-01-01

    A case of progressive irradiation-induced cerebral vasculopathy with abnormal netlike vessels and transdural anastomoses (moyamoya syndrome) is presented. Radiological findings in an additional 40 cases reported in the literature are analyzed, and their clinical relevance is discussed. A 19-year-old woman presented with recurrent ischemic brain lesions after radiation therapy for treatment of a craniopharyngioma during childhood. Cerebral angiography 6 and 12 years after completion of radiation therapy revealed progressive cerebral arterial occlusive disease involving the internal carotid artery on either side of the circle of Willis, with abnormal netlike vessels and transdural anastomoses (moyamoya syndrome). Extensive similarities between irradiation-induced cerebral vasculopathy and primary moyamoya syndrome (Nishimoto's disease) support the notion that both disorders share common pathophysiological mechanisms. The occurrence of moyamoya-like vascular changes may not depend on specific trigger mechanisms but may rather represent a nonspecific response of the developing vascular system to a number of various noxious events.

  19. Vascular Space Occupancy (VASO) Cerebral Blood Volume Weighted MRI Identifies Hemodynamic Impairment in Patients with Carotid Artery Disease

    PubMed Central

    Donahue, Manus J.; van Laar, Peter Jan; van Zijl, Peter C.M.; Stevens, Robert D.; Hendrikse, Jeroen

    2009-01-01

    Purpose To assess the role of vascular space occupancy (VASO) MRI, a non-invasive CBV-weighted technique, for evaluating CBV reactivity in patients with internal carotid artery (ICA) stenosis. Materials and Methods VASO reactivity, defined as signal change in response to hypercapnic stimulus (4s exhale, 14s breath hold), was measured in the left and right ICA flow territories in patients (n=10) with varying degrees of unilateral and bilateral ICA stenosis and in healthy volunteers (n=10). Results Percent VASO reactivity was more negative (P<0.01) bilaterally in patients (ipsilateral: −3.6±1.5%; contralateral: −3.4±1.2%) compared to age-matched controls (left: −1.9±0.6%; right: −1.9±0.8%). Owing to the nature of the VASO contrast mechanism, this more negative VASO reactivity was attributed to autoregulatory CBV effects in patients. A post-breath-hold overshoot, which was absent in healthy-volunteers, was observed unilaterally in a subset of patients. Conclusions More negative VASO reactivity was observed in patients with ICA stenosis and may be a marker of autoregulatory effects. Furthermore, the post-breath-hold overshoot observed in patients is consistent with compensatory microvascular vasoconstriction and may be a marker of hemodynamic impairment. Based on the results of this feasibility study, VASO should be useful for identifying CBV adjustments in patients with steno-occlusive disease of the ICA. PMID:19243067

  20. Rho kinase as a target for cerebral vascular disorders

    PubMed Central

    Bond, Lisa M; Sellers, James R; McKerracher, Lisa

    2015-01-01

    The development of novel pharmaceutical treatments for disorders of the cerebral vasculature is a serious unmet medical need. These vascular disorders are typified by a disruption in the delicate Rho signaling equilibrium within the blood vessel wall. In particular, Rho kinase overactivation in the smooth muscle and endothelial layers of the vessel wall results in cytoskeletal modifications that lead to reduced vascular integrity and abnormal vascular growth. Rho kinase is thus a promising target for the treatment of cerebral vascular disorders. Indeed, preclinical studies indicate that Rho kinase inhibition may reduce the formation/growth/rupture of both intracranial aneurysms and cerebral cavernous malformations. PMID:26062400

  1. Cerebral Blood Flow Alterations as Assessed by 3D ASL in Cognitive Impairment in Patients with Subcortical Vascular Cognitive Impairment: A Marker for Disease Severity

    PubMed Central

    Sun, Yawen; Cao, Wenwei; Ding, Weina; Wang, Yao; Han, Xu; Zhou, Yan; Xu, Qun; Zhang, Yong; Xu, Jianrong

    2016-01-01

    Abnormal reductions in cortical cerebral blood flow (CBF) have been identified in subcortical vascular cognitive impairment (SVCI). However, little is known about the pattern of CBF reduction in relation with the degree of cognitive impairment. CBF measured with three-dimensional (3D) Arterial Spin Labeling (ASL) perfusion magnetic resonance imaging (MRI) helps detect functional changes in subjects with SVCI. We aimed to compare CBF maps in subcortical ischemic vascular disease (SIVD) subjects with and without cognitive impairment and to detect the relationship of the regions of CBF reduction in the brain with the degree of cognitive impairment according to the z-score. A total of 53 subjects with SVCI and 23 matched SIVD subjects without cognitive impairment (controls), underwent a whole-brain 3D ASL MRI in the resting state. Regional CBF (rCBF) was compared voxel wise by using an analysis of variance design in a statistical parametric mapping program, with patient age and sex as covariates. Correlations were calculated between the rCBF value in the whole brain and the z-score in the 53 subjects with SVCI. Compared with the control subjects, SVCI group demonstrated diffuse decreased CBF in the brain. Significant positive correlations were determined in the rCBF values in the left hippocampus, left superior temporal pole gyrus, right superior frontal orbital lobe, right medial frontal orbital lobe, right middle temporal lobe, left thalamus and right insula with the z-scores in SVCI group. The noninvasively quantified resting CBF demonstrated altered CBF distributions in the SVCI brain. The deficit brain perfusions in the temporal and frontal lobe, hippocampus, thalamus and insula was related to the degree of cognitive impairment. Its relationship to cognition indicates the clinical relevance of this functional marker. Thus, our results provide further evidence for the mechanisms underlying the cognitive deficit in patients with SVCI. PMID:27630562

  2. Hereditary cerebral small vessel disease and stroke.

    PubMed

    Søndergaard, Christian Baastrup; Nielsen, Jørgen Erik; Hansen, Christine Krarup; Christensen, Hanne

    2017-04-01

    Cerebral small vessel disease is considered hereditary in about 5% of patients and is characterized by lacunar infarcts and white matter hyperintensities on MRI. Several monogenic hereditary diseases causing cerebral small vessel disease and stroke have been identified. The purpose of this systematic review is to provide a guide for determining when to consider molecular genetic testing in patients presenting with small vessel disease and stroke. CADASIL, CARASIL, collagen type IV mutations (including PADMAL), retinal vasculopathy with cerebral leukodystrophy, Fabry disease, hereditary cerebral hemorrhage with amyloidosis, and forkhead box C1 mutations are described in terms of genetics, pathology, clinical manifestation, imaging, and diagnosis. These monogenic disorders are often characterized by early-age stroke, but also by migraine, mood disturbances, vascular dementia and often gait disturbances. Some also present with extra-cerebral manifestations such as microangiopathy of the eyes and kidneys. Many present with clinically recognizable syndromes. Investigations include a thorough family medical history, medical history, neurological examination, neuroimaging, often supplemented by specific examinations e.g of the of vision, retinal changes, as well as kidney and heart function. However molecular genetic analysis is the final gold standard of diagnosis. There are increasing numbers of reports on new monogenic syndromes causing cerebral small vessel disease. Genetic counseling is important. Enzyme replacement therapy is possible in Fabry disease, but treatment options remain overall very limited.

  3. Cerebral Small Vessel Disease and Chronic Kidney Disease

    PubMed Central

    2015-01-01

    Chronic kidney disease, defined by a decreased glomerular filtration rate or albuminuria, is recognized as a major global health burden, mainly because it is an established risk factor for cardiovascular and cerebrovascular diseases. The magnitude of the effect of chronic kidney disease on incident stroke seems to be higher in persons of Asian ethnicity. Since the kidney and brain share unique susceptibilities to vascular injury due to similar anatomical and functional features of small artery diseases, kidney impairment can be predictive of the presence and severity of cerebral small vessel diseases. Chronic kidney disease has been reported to be associated with silent brain infarcts, cerebral white matter lesions, and cerebral microbleeds, independently of vascular risk factors. In addition, chronic kidney disease affects cognitive function, partly via the high prevalence of cerebral small vessel diseases. Retinal artery disease also has an independent relationship with chronic kidney disease and cognitive impairment. Stroke experts are no longer allowed to be ignorant of chronic kidney disease. Close liaison between neurologists and nephrologists can improve the management of cerebral small vessel diseases in kidney patients. PMID:25692105

  4. Pediatric neuroradiology: Cerebral and cranial diseases

    SciTech Connect

    Diebler, C.; Dulac, O.

    1987-01-01

    In this book, a neuroradiologist and a neuropediatrician have combined forces to provide the widest possible knowledge in investigating cranial and cerebral disorders in infancy and childhood. Based on more than 20,000 pediatric CT examinations, with a follow-up time often exceeding ten years, the book aims to bridge interdisciplinary gaps and help radiologists, pediatricians and neurosurgeons solve the various problems of pediatric neuroradiology that frequently confront them. For each disease, the etiology, clinical manifestation, pathological lesions and radiological presentations are discussed, supported by extensive illustrations. Malformative, vascular, traumatic, tumoral, infectious and metabolic diseases are reviewed. Miscellaneous conditions presenting particular symptoms or syndromes are also studied, such as hydrocephalus and neurological complications of leukemia. Contents: Cerebral and cranial malformations; neurocutaneous syndromes; inherited metabolic diseases; infectious diseases - vascular disorders; intracranial tumors; cranial trauma - miscellaneous and subject index.

  5. Vascular and metabolic reserve in Alzheimer's disease.

    PubMed

    Nagata, K; Kondoh, Y; Atchison, R; Sato, M; Satoh, Y; Watahiki, Y; Hirata, Y; Yokoyama, E

    2000-01-01

    Vascular and metabolic reserve were analyzed in probable Alzheimer's disease (AD) and vascular dementia (VaD). Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and oxygen extraction fraction (OEF) were measured quantitatively with positron emission tomography (PET). Vascular reactivity (VR) was also calculated by comparing the CBF during 5% CO(2) inhalation with the CBF during normal breathing. Vascular transit time (VTT) that was calculated as a ratio of CBV/CBF and VR reflect vasodilating capacity of the small resistance vessels, whereas OEF designates metabolic (oxygen-extraction) reserve in threatening brain ischemia. Significant increase in OEF was seen in the parieto-temporal cortex and both VTT and VR were preserved in AD patients. By constrast, there was no significant increase in OEF whereas VTT was prolonged and VR was markedly depressed in VaD patients. The increase of OEF and preserved VTT and VR seen in AD patients indicate the possible participation of vascular factors in the pathogenesis of AD perhaps at the capillary level.

  6. Are low levels of HDL2-cholesterol a risk factor for atherosclerosis of cerebral vascular disease? Case report.

    PubMed

    Cordova, C; Alessandri, C; Basili, S; Peverini, F; Ferro, D; Barsi, R; Paradiso, M

    1990-01-01

    A case of a 45 years old man with an atherosclerotic stenosis of right internal carotid and TIA event is reported. The patient showed an increase of total cholesterol and LDL-cholesterol serum levels and, in particular, a very low familiar HDL2-cholesterol serum value. The possibility that this last condition could represent an important co-factor of the extracranial cerebrovascular disease is discussed. The usefulness of a long-term follow-up of all family members, showing the same lipids pattern, is also suggested.

  7. Supravalvular aortic stenosis associated to infectious endocarditis and cerebral vascular disease in a patient with Williams-Beuren Syndrome.

    PubMed

    De Rubens Figueroa, Jesús; Marhx, Alfonso; López Terrazas, Javier; Palacios Macedo, Alexis

    2015-01-01

    The Williams-Beuren syndrome is a rare genetic disease characterized by: (a) typical facial features; (b) psychomotor retardation with a specific neurocognitive profile; (c) cardiovascular condition and (d) likely transient hypocalcemia in infancy. The objective of this study was to describe the clinic evolution and diagnosis of patient with this syndrome that was associated with endocarditis caused by Streptococcus parasanguis in the ascending aorta and an aneurism located in the fronto-temporal area, which produced a parenchymal hematoma in the left lobe, and subarachnoid hemorrhage. He was treated with ceftriaxone and dicloxacillin. Then we proceeded to correct the aneurysm and perform vegetation resection in aortic arteries with supravalvular aortic stenosis correction. The evolution after one year has been favorable and is currently without neurologic sequelae. A 5-year-old male patient presented a diagnosis of supravalvular aortic stenosis. After cardiac catheterization was performed, he presented a fever and right side paresis. The echocardiogram showed multiple vegetations in the ascendant aortic arch and the supraortic arteries. The blood cultures reported S. parasanguis. The magnetic resonance showed a subarachnoid hemorrhage with an aneurysm and a hematoma. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  8. Calcium intake, vascular calcification, and vascular disease.

    PubMed

    Spence, Lisa A; Weaver, Connie M

    2013-01-01

    Recent research has reported a possible link between calcium supplementation and increased risk of cardiovascular disease and its endpoints in healthy, older adults. To evaluate the current evidence regarding the impact of calcium supplementation on cardiovascular disease risk and to address research gaps, the present review was conducted. Systematic reviews and meta-analyses were included, when available, along with original articles. The articles included in the review were obtained from PubMed using the following search terms: calcium intake, calcium supplementation, cardiovascular disease, myocardial infarction, mortality, and vascular calcification. The majority of the studies reviewed demonstrated no statistically significant adverse or beneficial effect of calcium supplementation on cardiovascular disease or its endpoints. While some studies indicate a possible increased risk, there is a lack of consensus on these findings and a need exists to further elucidate a mechanism. More experimental data are necessary to understand the impact of calcium intake, both levels and sources, on vascular calcification and vascular disease. The use of (41)C kinetic modeling in the Ossabaw swine provides an approach for assessing soft tissue calcification in an atherosclerotic and normal state to address research gaps.

  9. Cerebral vascular aging: extending the concept of pulse wave encephalopathy through capillaries to the cerebral veins.

    PubMed

    Henry-Feugeas, Marie Cecile; Koskas, Pierre

    2012-07-01

    The recent concept of pulse wave encephalopathy helps understanding the cerebral venous remodeling in aging. This so-called periventricular venous collagenosis is an expected mechanical consequence of the age-related changes in arterial pulsations and the mechanical fatigue of vascular smooth muscles. Unlike arteriolar mechanical stress, venular mechanical stress depends on both the blood pulse wave amplitude and the mechanical properties of the environment tissue. Thereby, there is a preferential periventricular location of venous collagenosis and a mechanistic link between venous collagenosis and foci of white matter rarefaction or leukoaraiosis. The recent concept of pulse wave encephalopathy also helps understanding the widening of retinal venules, the "mirror" of cerebral venules, in various manifestations of pulse wave encephalopathy, including progressive leukoara�osis, lacunar and hemorrhagic "pulse wave" strokes, and dementia. Indeed, the age-related chronic increase in arterial pulsations explains subsequent arteriolar myogenic "fatigue", marked attenuation in the arteriolar myogenic tone and abnormal penetration of the insufficiently dampened arterial pulse wave into the venules. Thus, retinal venular widening, a biomarker of advanced pulse wave encephalopathy, is also increasingly recognized as a biomarker for high cardiovascular risk. All these data support a shift in the concept of chronic cerebrovascular disease, from the classical model which is restricted to steno-occlusive cerebrovascular diseases to an enlarged model which would include the pulse wave encephalopathy concept. Thereby, preventing damage to the cerebral microvasculature by an undampened arterial pulse wave will become a logical target for the prevention and treatment of late-onset cognitive decline.

  10. Pediatric Stroke: The Importance of Cerebral Arteriopathy and Vascular Malformations

    PubMed Central

    Beslow, Lauren A.; Jordan, Lori C.

    2011-01-01

    Stroke is an important cause of neurologic morbidity in childhood. Population-based estimates of the annual incidence of childhood stroke range from 2 to 13 per 100,000 children. This article will review recent literature on both hemorrhagic and ischemic stroke in children with a focus on cerebral arteriopathy and vascular malformations as stroke risk factors. Additional risk factors include congenital heart disease, sickle cell disease, and hematologic abnormalities among others. Outcomes are variable and are related to the severity of presentation, associated illnesses, and other factors. More than half of children who have had a stroke have long-term neurological sequelae. Five-year recurrence risk is estimated to be 5–19%. Children with cerebrovascular abnormalities are at the highest risk of recurrence (66% at 5 years for ischemic stroke in one study). Furthermore, cerebral arteriopathy including arterial dissection may account for up to 80% of childhood stroke in otherwise healthy children. In many cases, evaluation and treatment of pediatric stroke is not evidence-based, and regional and geographic variations in practice patterns exist. Multicenter cohort studies and ultimately dedicated pediatric clinical trials will be essential to establish comprehensive evidence-based guidelines for pediatric stroke care. PMID:20625743

  11. Vascular dysfunction as a target for adjuvant therapy in cerebral malaria

    PubMed Central

    Carvalho, Leonardo José de Moura; Moreira, Aline da Silva; Daniel-Ribeiro, Cláudio Tadeu; Martins, Yuri Chaves

    2014-01-01

    Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum malaria that continues to be a major global health problem. Brain vascular dysfunction is a main factor underlying the pathogenesis of CM and can be a target for the development of adjuvant therapies for the disease. Vascular occlusion by parasitised red blood cells and vasoconstriction/vascular dysfunction results in impaired cerebral blood flow, ischaemia, hypoxia, acidosis and death. In this review, we discuss the mechanisms of vascular dysfunction in CM and the roles of low nitric oxide bioavailability, high levels of endothelin-1 and dysfunction of the angiopoietin-Tie2 axis. We also discuss the usefulness and relevance of the murine experimental model of CM by Plasmodium berghei ANKA to identify mechanisms of disease and to screen potential therapeutic interventions. PMID:25185000

  12. Cerebral hydatid disease in Britain

    PubMed Central

    Anderson, Milne; Bickerstaff, Edwin R.; Hamilton, J. G.

    1975-01-01

    Two cases of cerebral hydatid disease are described. This condition, acquired by Britons in Britain, is extremely rare as only two similar cases have been reported before. Details of clinical presentation, investigation and treatment are described. Images PMID:1206419

  13. [Ischemic cerebral vascular stroke after heroin sniffing. A new case].

    PubMed

    Bartolomei, F; Nicoli, F; Swiader, L; Gastaut, J L

    1992-06-06

    Three hours after sniffing a dose of heroin, a 30-year old man developed right hemiplegia with aphasia. Magnetic resonance imaging of the brain showed an infarct in the territory of the left anterior choroid artery. Cerebral vascular accidents occurring as complications of heroin addiction are rare: a review of the literature yielded only 13 documented cases. The main characteristics of these strokes are analysed and their pathogenetic mechanisms (immuno-allergic vasculitis, vascular spasm) are discussed.

  14. Cerebral hemodynamics and endothelial function in patients with Fabry disease.

    PubMed

    Segura, Tomás; Ayo-Martín, Oscar; Gómez-Fernandez, Isabel; Andrés, Carolina; Barba, Miguel A; Vivancos, José

    2013-11-11

    Cerebral vasculopathy have been described in Fabry disease, in which altered cerebral blood flow, vascular remodelling or impairment of endothelial function could be involved. Our study aims to evaluate these three possibilities in a group of Fabry patients, and compare it to healthy controls. Cerebral hemodynamics, vascular remodelling and systemic endothelial function were investigated in 10 Fabry patients and compared to data from 17 healthy controls. Transcranial Doppler was used to study blood flow velocity of intracranial arteries and cerebral vasomotor reactivity. For the study of vascular remodelling and endothelial function, intima-media thickness of common carotid arteries, flow-mediated dilation in brachial artery and serum levels of soluble VCAM-1, TNF-α, high-sensitive CRP and IL-6 were measured. Differences between groups were evaluated using appropriate tests. No relevant differences were observed in cerebral hemodynamic parameters, intima-media thickness or flow-mediated dilation. There was a trend for low serum levels of IL-6 and high serum levels of TNF-α and high-sensitive CRP in Fabry patients; plasma concentrations of soluble VCAM-1 were significantly higher in Fabry disease patients than in healthy volunteers (p = 0.02). In our sample, we did not find relevant alterations of cerebral hemodynamics in Fabry disease patients. Increased levels of plasmatic endothelial biomarkers seem to be the most important feature indicative of possible vascular dysfunction in Fabry disease patients.

  15. Cerebral hemodynamics and endothelial function in patients with Fabry disease

    PubMed Central

    2013-01-01

    Background Cerebral vasculopathy have been described in Fabry disease, in which altered cerebral blood flow, vascular remodelling or impairment of endothelial function could be involved. Our study aims to evaluate these three possibilities in a group of Fabry patients, and compare it to healthy controls. Methods Cerebral hemodynamics, vascular remodelling and systemic endothelial function were investigated in 10 Fabry patients and compared to data from 17 healthy controls. Transcranial Doppler was used to study blood flow velocity of intracranial arteries and cerebral vasomotor reactivity. For the study of vascular remodelling and endothelial function, intima-media thickness of common carotid arteries, flow-mediated dilation in brachial artery and serum levels of soluble VCAM-1, TNF-α, high-sensitive CRP and IL-6 were measured. Differences between groups were evaluated using appropriate tests. Results No relevant differences were observed in cerebral hemodynamic parameters, intima-media thickness or flow-mediated dilation. There was a trend for low serum levels of IL-6 and high serum levels of TNF-α and high-sensitive CRP in Fabry patients; plasma concentrations of soluble VCAM-1 were significantly higher in Fabry disease patients than in healthy volunteers (p = 0.02). Conclusions In our sample, we did not find relevant alterations of cerebral hemodynamics in Fabry disease patients. Increased levels of plasmatic endothelial biomarkers seem to be the most important feature indicative of possible vascular dysfunction in Fabry disease patients. PMID:24207059

  16. Demographic Features and Neuropsychological Correlates in a Cohort of 200 Patients with Vascular Cognitive Decline Due to Cerebral Small Vessel Disease

    PubMed Central

    Issac, Thomas Gregor; Chandra, Sadanandavalli Retnaswami; Rajeswaran, Jamuna; Christopher, Rita; Philip, Mariamma

    2016-01-01

    Introduction: Vascular dementia is the second most common form of dementia and is potentially reversible. Small vessel disease (SVD) closely mimics degenerative dementia in view of its sub-acute onset and progressive course. Therefore, unlike large vessel disease, Hachinski Ischemic scale score may not always reflect vascular cognitive decline resulting in diagnostic and therapeutic confusions. Therefore, there is a need for detailed neuropsychological assessment for various cognitive domains for early identification of vascular cognitive decline as it carries a very good long term prognosis for cognitive morbidity, unlike degenerative dementias. Patients and Methods: This prospective study involves thorough domain based neuropsychological assessment of patients with a radiological diagnosis of SVD involving the following parameters-digit forward and backward, category fluency, color trails, stick test, logical memory test, and bender gestalt test. Magnetic resonance imaging scans done using 3-tesla machines and SVD graded using Fazekas visual scale. Results: The mean Hachinskis score was less sensitive for differentiating vascular dementia from degenerative dementia. However, the domain based neuropsychological scores were highly sensitive showing statistically significant impairment in all 6 domains tested and compared with Fazekas 1-3 grades in imaging. Discussion and Conclusion: This study aimed at establishing an early diagnosis of vascular mild cognitive impairment using domain wise neuropsychological testing and correlating it with radiological scores. Hachinskis score is more sensitive for large vessel disease in view of acute onset and step-like progression as against steady progression in SVD. However, domain-wise testing was highly sensitive in identifying early cognitive impairment in patients with SVD, and early therapeutic interventions are highly rewarding. PMID:27114624

  17. Association factor analysis between osteoporosis with cerebral artery disease

    PubMed Central

    Jin, Eun-Sun; Jeong, Je Hoon; Lee, Bora; Im, Soo Bin

    2017-01-01

    Abstract The purpose of this study was to determine the clinical association factors between osteoporosis and cerebral artery disease in Korean population. Two hundred nineteen postmenopausal women and men undergoing cerebral computed tomography angiography were enrolled in this study to evaluate the cerebral artery disease by cross-sectional study. Cerebral artery disease was diagnosed if there was narrowing of 50% higher diameter in one or more cerebral vessel artery or presence of vascular calcification. History of osteoporotic fracture was assessed using medical record, and radiographic data such as simple radiography, MRI, and bone scan. Bone mineral density was checked by dual-energy x-ray absorptiometry. We reviewed clinical characteristics in all patients and also performed subgroup analysis for total or extracranial/ intracranial cerebral artery disease group retrospectively. We performed statistical analysis by means of chi-square test or Fisher's exact test for categorical variables and Student's t-test or Wilcoxon's rank sum test for continuous variables. We also used univariate and multivariate logistic regression analyses were conducted to assess the factors associated with the prevalence of cerebral artery disease. A two-tailed p-value of less than 0.05 was considered as statistically significant. All statistical analyses were performed using R (version 3.1.3; The R Foundation for Statistical Computing, Vienna, Austria) and SPSS (version 14.0; SPSS, Inc, Chicago, Ill, USA). Of the 219 patients, 142 had cerebral artery disease. All vertebral fracture was observed in 29 (13.24%) patients. There was significant difference in hip fracture according to the presence or absence of cerebral artery disease. In logistic regression analysis, osteoporotic hip fracture was significantly associated with extracranial cerebral artery disease after adjusting for multiple risk factors. Females with osteoporotic hip fracture were associated with total calcified

  18. MR imaging of cerebral vascular malformations.

    PubMed

    Lee, B C; Herzberg, L; Zimmerman, R D; Deck, M D

    1985-01-01

    Fifteen vascular malformations, including six supratentorial arteriovenous malformations (AVMs), three venous malformations, and six brainstem vascular malformations, were examined on 0.5 T magnetic resonance (MR) and GE 9800 and 8800 computed tomographic (CT) scanners. All the malformations were shown by MR, and the arterial and venous drainage of AVMs was precisely delineated. Hematoma was always differentiated from calcification by MR signal characteristics. Increased signal in the brain parenchyma was often seen adjacent to AVMs. The signal of blood within venous malformations altered with spin-echo techniques using various repetition times and was distinguished from rapidly flowing blood in AVMs that lacked signal in all imaging sequences. Brainstem malformations were seldom demonstrated by angiography. Hemorrhage was common and was invariably associated with multiple areas of absent signal that may have represented abnormal vessels. These appearances are distinct from those of intrinsic tumors and are probably pathognomonic of brainstem vascular malformations.

  19. Amputation in vascular disease.

    PubMed Central

    Robinson, K.

    1980-01-01

    The management of vascular amputees in the Roehampton Limb Surgery Unit since its opening in 1975 is outlined and the results in 167 cases presented. Of the 35 patients over the age of 80, 57% were walking independently at the time of their discharge from the unit. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7377693

  20. Evaluation of Bioenergetic Function in Cerebral Vascular Endothelial Cells.

    PubMed

    Rellick, Stephanie L; Hu, Heng; Simpkins, James W; Ren, Xuefang

    2016-11-19

    The integrity of the blood-brain-barrier (BBB) is critical to prevent brain injury. Cerebral vascular endothelial (CVE) cells are one of the cell types that comprise the BBB; these cells have a very high-energy demand, which requires optimal mitochondrial function. In the case of disease or injury, the mitochondrial function in these cells can be altered, resulting in disease or the opening of the BBB. In this manuscript, we introduce a method to measure mitochondrial function in CVE cells by using whole, intact cells and a bioanalyzer. A mito-stress assay is used to challenge the cells that have been perturbed, either physically or chemically, and evaluate their bioenergetic function. Additionally, this method also provides a useful way to screen new therapeutics that have direct effects on mitochondrial function. We have optimized the cell density necessary to yield oxygen consumption rates that allow for the calculation of a variety of mitochondrial parameters, including ATP production, maximal respiration, and spare capacity. We also show the sensitivity of the assay by demonstrating that the introduction of the microRNA, miR-34a, leads to a pronounced and detectable decrease in mitochondrial activity. While the data shown in this paper is optimized for the bEnd.3 cell line, we have also optimized the protocol for primary CVE cells, further suggesting the utility in preclinical and clinical models.

  1. [Aging and retinal vascular diseases].

    PubMed

    Takagi, Hitoshi

    2007-03-01

    Ocular vascular diseases such as diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration, whose population increases along with aging, have become leading causes of severe visual disturbance. Macular edema and serous retinal detachment are associated with abnormal vascular leakage and tractional retinal detachment, and neovascular glaucoma is caused by retinal neovascularization. Such ocular vascular diseases are caused by vascular cell aging and vascular damage associated with lifestyle-related diseases including diabetes mellitus, hypertension, hyperlipidemia, and obesity. In the present study, we investigated molecular mechanisms in such vascular deficiencies using vascular cell biology methodology, and we propose novel strategies for the treatment of such vascular diseases. Along with aging, oxidative stress and physical stress, such as mechanical stretch, continuously and directly insult vascular cells. Such stress induces apoptosis by intracellular signaling through stress kinases in cultured retinal vascular cells. Inhibition of such stress kinases could be an effective treatment to protect the vascular cells against age-related damage. In a retinal vascular developmental model, pericyte loss causes pathology mimicking macular edema and proliferative diabetic retinopathy. Angiopoietin 1 (Ang 1) secreted by pericytes suppresses oxidative stress-induced intracellular signaling through stress kinases linked to cell apoptosis and normalizes such retinal pathology. This suggests that the paracrine action of Ang 1 in the pericytes is necessary to sustain normal retinal vasculature, and that Ang 1-triggered intracellular signaling is useful for the treatment of vascular cell pathology associated with pericyte loss. In diabetic retinopathy and retinal vein occlusion, retinal vessels regress along with retinal vascular cell apoptosis, and the retina becomes ischemic followed by pathological retinal neovascularization. VEGF has been

  2. Soluble Endoglin Modulates Aberrant Cerebral Vascular Remodeling

    PubMed Central

    Chen, Yongmei; Hao, Qi; Kim, Helen; Su, Hua; Letarte, Michelle; Karumanchi, S. Ananth; Lawton, Michael T.; Barbaro, Nicholas M.; Yang, Guo-Yuan; Young, William L.

    2009-01-01

    Objective Brain arteriovenous malformations (AVMs) are an important cause of neurological morbidity in young adults. The pathophysiology of these lesions is poorly understood. A soluble form of endoglin (sEng) has been shown to cause endothelial dysfunction and induce preeclampsia. We tested if sEng would be elevated in brain AVM tissues relative to epilepsy brain tissues, and also investigated whether sEng overexpression via gene transfer in the mouse brain would induce vascular dysplasia and associated changes in downstream signaling pathways. Methods Expression levels of sEng in surgical specimens were determined by Western blot assay and ELISA. Vascular dysplasia, levels of MMP and oxidative stress were determined by immunohistochemistry and gelatin zymography. Results Brain AVMs (n=33) had higher mean sEng levels (245 ± 175 vs 100 ± 60, % of control, P=0.04) compared with controls (n=8), as determined by Western blot. In contrast, membrane-bound Eng was not significantly different (108 ± 79 vs 100 ± 63, % of control, P=0.95). sEng gene transduction in the mouse brain induced abnormal vascular structures. It also increased matrix metalloproteinase (MMP) activity by 490 ± 30% (MMP-9), 220 ± 30% (MMP-2), and oxidants by 260 ± 20% (4-hydroxy-2-nonenal) at 2 weeks after injection, suggesting that MMPs and oxidative radicals may mediate sEng-induced pathological vascular remodeling. Interpretation The results suggest that elevated sEng may play a role in the generation of sporadic brain AVMs. Our findings may provide new targets for therapeutic intervention for patients with brain AVMs. PMID:19670444

  3. Cerebral vascular regulation and brain injury in preterm infants.

    PubMed

    Brew, Nadine; Walker, David; Wong, Flora Y

    2014-06-01

    Cerebrovascular lesions, mainly germinal matrix hemorrhage and ischemic injury to the periventricular white matter, are major causes of adverse neurodevelopmental outcome in preterm infants. Cerebrovascular lesions and neuromorbidity increase with decreasing gestational age, with the white matter predominantly affected. Developmental immaturity in the cerebral circulation, including ongoing angiogenesis and vasoregulatory immaturity, plays a major role in the severity and pattern of preterm brain injury. Prevention of this injury requires insight into pathogenesis. Cerebral blood flow (CBF) is low in the preterm white matter, which also has blunted vasoreactivity compared with other brain regions. Vasoreactivity in the preterm brain to cerebral perfusion pressure, oxygen, carbon dioxide, and neuronal metabolism is also immature. This could be related to immaturity of both the vasculature and vasoactive signaling. Other pathologies arising from preterm birth and the neonatal intensive care environment itself may contribute to impaired vasoreactivity and ineffective CBF regulation, resulting in the marked variations in cerebral hemodynamics reported both within and between infants depending on their clinical condition. Many gaps exist in our understanding of how neonatal treatment procedures and medications have an impact on cerebral hemodynamics and preterm brain injury. Future research directions for neuroprotective strategies include establishing cotside, real-time clinical reference values for cerebral hemodynamics and vasoregulatory capacity and to demonstrate that these thresholds improve long-term outcomes for the preterm infant. In addition, stimulation of vascular development and repair with growth factor and cell-based therapies also hold promise.

  4. Cerebral Gluconeogenesis and Diseases

    PubMed Central

    Yip, James; Geng, Xiaokun; Shen, Jiamei; Ding, Yuchuan

    2017-01-01

    The gluconeogenesis pathway, which has been known to normally present in the liver, kidney, intestine, or muscle, has four irreversible steps catalyzed by the enzymes: pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase, and glucose 6-phosphatase. Studies have also demonstrated evidence that gluconeogenesis exists in brain astrocytes but no convincing data have yet been found in neurons. Astrocytes exhibit significant 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 activity, a key mechanism for regulating glycolysis and gluconeogenesis. Astrocytes are unique in that they use glycolysis to produce lactate, which is then shuttled into neurons and used as gluconeogenic precursors for reduction. This gluconeogenesis pathway found in astrocytes is becoming more recognized as an important alternative glucose source for neurons, specifically in ischemic stroke and brain tumor. Further studies are needed to discover how the gluconeogenesis pathway is controlled in the brain, which may lead to the development of therapeutic targets to control energy levels and cellular survival in ischemic stroke patients, or inhibit gluconeogenesis in brain tumors to promote malignant cell death and tumor regression. While there are extensive studies on the mechanisms of cerebral glycolysis in ischemic stroke and brain tumors, studies on cerebral gluconeogenesis are limited. Here, we review studies done to date regarding gluconeogenesis to evaluate whether this metabolic pathway is beneficial or detrimental to the brain under these pathological conditions. PMID:28101056

  5. Cerebral vascular accident: some characteristics of occupational therapy evaluation forms.

    PubMed

    Ottenbacher, K

    1980-04-01

    To determine areas most commonly evaluated by occupational therapists and to ascertain methods in which evaluative information is gathered, 35 evaluation forms currently employed by occupational therapists to assess dysfunction in patients with cerebral vascular accident were collected. Five general areas including motor function, sensory deficit, hadn function, activities of daily living, and visual perception were found to be most frequently listed on the forms. These areas were divided into sub areas to operationally define the information collected. Analysis revealed that the level of measurement most frequently employed by therapists to record evaluate findings was the descriptive level. There was a tendency to collect data at "higher" or more sophisticated levels of measurement in those areas evaluated most frequently. The findings are discussed in relation to professional competency concerns and the need to develop unique occupational therapy evaluative instruments for areas of practice such as cerebral vascular accident.

  6. Cerebral vasospasm. Part I. In cerebral vascular malformations.

    PubMed

    Mohr, J P; Kase, C S

    1983-01-01

    This review enumerates the many proposed mechanisms of vasospasm, including cellular elements, agents derived from the blood and injured cerebral tissues, alteration of calcium: magnesium ratios, free radical reactions, hypothalamic injury, clogging of the subarachnoid space, obstructions of the vasa vasorum and necrosis of the media with subintimal proliferation and intraluminal acidosis. At present, no single agent has been demonstrated as the only source of vasospasm, and whether the disorder is spasm or a chronic arteriopathy remains the subject of argument. The factors influencing the frequency, timing, severity and distribution of angiographically documented vasospasm are discussed, including data from our own population-based study over a 3 year period showing an incidence of vasospasm of 73%. Special emphasis is given to the observation that differences in patient populations play a major role in the incidence and severity of reported vasospasm: those from non-selective populations show a higher incidence of vasospasm and a greater severity of the syndromes attributed to spasm. Hypotheses are offered to account for the low frequency of vasospasm in hemorrhages from arteriovenous malformations and mycotic aneurysms. Clinical syndromes of vasospasm are reviewed, with special emphasis on our own material. The mode of onset and subsequent course of syndromes include those of sudden onset consistent with embolism, and those of gradual onset suggesting a low flow state. Their relationship to the severity of the subarachnoid hemorrhage and the vasospasm is presented. The paucity of syndromes of isolated deep infarcts of the lacunar type is noted. An account is given of the many failed therapies and the future hopes for early surgery. Innovations in medical therapy, including the use of some platelet inhibitors available only in some countries, and rationales for the use of aspirin and even heparin is discussed.

  7. Effect of age and vascular anatomy on blood flow in major cerebral vessels.

    PubMed

    Amin-Hanjani, Sepideh; Du, Xinjian; Pandey, Dilip K; Thulborn, Keith R; Charbel, Fady T

    2015-02-01

    Measurement of volume flow rates in major cerebral vessels can be used to evaluate the hemodynamic effects of cerebrovascular disease. However, both age and vascular anatomy can affect flow rates independent of disease. We prospectively evaluated 325 healthy adult volunteers using phase contrast quantitative magnetic resonance angiography to characterize these effects on cerebral vessel flow rates and establish clinically useful normative reference values. Flows were measured in the major intracranial and extracranial vessels. The cohort ranged from 18 to 84 years old, with 157 (48%) females. All individual vessel flows and total cerebral blood flow (TCBF) declined with age, at 2.6 mL/minute per year for TCBF. Basilar artery (BA) flow was significantly decreased in individuals with one or both fetal posterior cerebral arteries (PCAs). Internal carotid artery flows were significantly higher with a fetal PCA and decreased with a hypoplastic anterior cerebral artery. Indexing vessel flows to TCBF neutralized the age effect, but anatomic variations continued to impact indexed flow in the BA and internal carotid artery. Variability in normative flow ranges were reduced in distal vessels and by examining regional flows. Cerebral vessel flows are affected by age and cerebrovascular anatomy, which has important implications for interpretation of flows in the disease state.

  8. Akt isoforms in vascular disease

    PubMed Central

    Yu, Haixiang; Littlewood, Trevor; Bennett, Martin

    2015-01-01

    The mammalian serine/threonine Akt kinases comprise three closely related isoforms: Akt1, Akt2 and Akt3. Akt activation has been implicated in both normal and disease processes, including in development and metabolism, as well as cancer and cardiovascular disease. Although Akt signalling has been identified as a promising therapeutic target in cancer, its role in cardiovascular disease is less clear. Importantly, accumulating evidence suggests that the three Akt isoforms exhibit distinct tissue expression profiles, localise to different subcellular compartments, and have unique modes of activation. Consistent with in vitro findings, genetic studies in mice show distinct effects of individual Akt isoforms on the pathophysiology of cardiovascular disease. This review summarises recent studies of individual Akt isoforms in atherosclerosis, vascular remodelling and aneurysm formation, to provide a comprehensive overview of Akt function in vascular disease. PMID:25929188

  9. Cerebral vascular reactivity on return from the International Space Station

    NASA Astrophysics Data System (ADS)

    Zuj, Kathryn; Greaves, Danielle; Shoemaker, Kevin; Blaber, Andrew; Hughson, Richard L.

    Returning from spaceflight, astronauts experience a high incidence of orthostatic intolerance and syncope. Longer duration space flight may result in greater adaptations to microgravity which could increase the post-flight incidence of syncope. CCISS (Cardiovascular and Cerebovascular Control on return from the International Space Station) is an ongoing project designed to help determine adaptations that occur during spaceflight which may contribute to orthostatic intolerance. One component of this project involves looking at cerebral vascular responses before and after long duration spaceflight. As a known vasodilator, carbon dioxide (CO2) has been frequently used to assess changes in cerebral vascular reactivity. In this experiment, end tidal PCO2 was manipulated through changes in respired air. Two breaths of a 10% CO2 gas mixture were administered at 1-min intervals resulting in an increase in end tidal PCO2 . Throughout the testing, cerebral blood flow velocity (CBFV) was determined using transcranial Doppler ultrasound. The cerebral resistance index (RI) was calculated from the Doppler wave form using the equation; RI=(CBFVsystolic-CBFVdiastolic)/CBFVsystolic. Changes in this index have been shown to reflect changes in cerebral vascular resistance. Peak responses to the CO2 stimulus were determined and compared to baseline measures taken at the beginning of the testing. Cerebral blood flow velocity increased and RI decreased with the two breaths of CO2. Preliminary data show a 36.0% increase in CBFV and a 9.0% decrease in RI pre-flight. Post flight, the response to CO2 appears to change showing a potentially blunted decrease in resistance (6.8%) and a smaller increase in CBFV (22.8%). Long term spaceflight may result in cerebrovascular changes which could decrease the vasodilatory capacity of cerebral resistance vessels. Further investigations in the CCISS project will reveal the interactive role of CO2 and arterial blood pressure on maintenance of brain

  10. Atherosclerotic risk factors, vascular cognitive impairment, and Alzheimer disease.

    PubMed

    Kovacic, Jason C; Fuster, Valentin

    2012-01-01

    The involvement of vascular factors in Alzheimer dementia was first appreciated over 100 years ago. Recently, significant advances in our understanding of these brain-vascular relationships have taken place. Vascular cognitive impairment is now recognized as a distinct group of interrelated vascular-based neurological insults that can accumulate and lead to dementia. Importantly, the pathology of vascular cognitive impairment extends far beyond brain destruction wrought by major stroke. Other subtle changes may also arise that contribute to vascular cognitive impairment and dementia, including subclinical stroke, white-matter changes such as hyperintensities and lipohyalinosis, small lacunar infarcts, cerebral hypoperfusion, and compromise of the blood-brain barrier. In this review we critically examine the emerging body of evidence that relates atherosclerotic risk factors, brain functioning, and Alzheimer disease. © 2012 Mount Sinai School of Medicine.

  11. Cocaine induces apoptosis in cerebral vascular muscle cells: potential roles in strokes and brain damage.

    PubMed

    Su, Jialin; Li, Jianfeng; Li, Wenyan; Altura, Bella T; Altura, Burton M

    2003-12-15

    Cocaine abuse is known to induce different types of brain-microvascular damage and many adverse cerebrovascular effects, including cerebral vasculitis, intracranial hemorrhage, cerebral infarction and stroke. A major physiological event leading to these pathophysiological actions of cocaine could be apoptosis. Whether cocaine can cause brain-microvascular pathology and vascular toxicity by inducing apoptosis of cerebral vascular smooth muscle cells is not known. This study, using several different methods to discern apoptosis, was designed to investigate if primary cultured canine cerebral vascular smooth muscle cells can undergo apoptosis when treated with cocaine. After treatment with cocaine (10(-6)-10(-3) M) for 12-24 h, the death rates of cerebral vascular smooth muscle cells increased in a concentration-dependent manner compared with controls. Morphological analysis of cerebral vascular smooth muscle cells using confocal fluoresence microscopy showed that the percentage of apoptotic cerebral vascular smooth muscle cells increased after cocaine (10(-6)-10(-3) M) treatment in a concentration-dependent manner. TUNEL assays also showed positive results for cerebral vascular smooth muscle cells treated with cocaine. These results clearly demonstrate that cerebral vascular smooth muscle cells can undergo rapid apoptosis in response to cocaine in a concentration-dependent manner. Cocaine-induced apoptosis may thus play a major role in brain-microvascular damage, cerebral vascular toxicity and strokes.

  12. Cerebral microbleeds in patients with mild cognitive impairment and small vessel disease: The Vascular Mild Cognitive Impairment (VMCI)-Tuscany study.

    PubMed

    Valenti, Raffaella; Del Bene, Alessandra; Poggesi, Anna; Ginestroni, Andrea; Salvadori, Emilia; Pracucci, Giovanni; Ciolli, Laura; Marini, Sandro; Nannucci, Serena; Pasi, Marco; Pescini, Francesca; Diciotti, Stefano; Orlandi, Giovanni; Cosottini, Mirco; Chiti, Alberto; Mascalchi, Mario; Bonuccelli, Ubaldo; Inzitari, Domenico; Pantoni, Leonardo

    2016-09-15

    Cerebral microbleeds (CMBs) are a neuroimaging expression of small vessel disease (SVD). We investigated in a cohort of SVD patients with mild cognitive impairment (MCI): 1) the reliability of the Microbleed Anatomical Rating Scale (MARS); 2) the burden and location of CMBs and their association with cognitive performances, independent of other clinical and neuroimaging features. Patients underwent clinical, neuropsychological (4 cognitive domains), and MRI assessments. CMBs were assessed by three raters. Out of the 152 patients (57.2% males; mean age±SD: 75.5±6.7years) with gradient-echo (GRE) sequences, 41 (27%) had at least one CMB. Inter-rater agreement for number and location of CMBs ranged from good to very good [multi-rater Fleiss kappa (95%CI): 0.70-0.95]. Lacunar infarcts and some clinical variables (e.g., hypertension and physical activity) were associated with CMBs in specific regions. Total number of CMBs and of those in deep and lobar regions were associated with attention/executive and fluency domains. MARS is a reliable instrument to assess CMBs in SVD patients with MCI. Nearly one third of these patients had at least one CMB. Total CMBs burden was associated with attention/executive functions and fluency domains impairment, lacunar infarcts, and with some potentially modifiable risk factors. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Monitoring cerebral oxygenation in a pediatric patient undergoing surgery for vascular ring.

    PubMed

    Joshi, Reena K; Motta, Pablo; Horibe, Mayumi; Mossad, Emad

    2006-02-01

    Regional cerebral oxygenation can be monitored using near-infrared spectroscopy (NIRS). Inadequacy of collateral cerebral circulation and regional cerebral ischemia during cardiac and vascular surgery may be detected by the use of NIRS monitoring. We report a 2-year-old child who underwent surgical repair of vascular ring and subclavian reimplantation, where use of NIRS helped in early detection and timely intervention to prevent prolonged cerebral ischemia.

  14. [Cerebral hydatid disease: imaging features].

    PubMed

    Tlili-Graiess, K; El-Ouni, F; Gharbi-Jemni, H; Arifa, N; Moulahi, H; Mrad-Dali, K; Guesmi, H; Abroug, S; Yacoub, M; Krifa, H

    2006-12-01

    Cerebral hytatid cysts (HC) are extremely rare, forming 2% of all intra cranial space occupying lesions even in counties where the disease is endemic. HC diagnosis is usually based on a pathognomonic computed tomography (CT) pattern. In order to assess the value of MR we reviewed the CT (n=25) and magnetic resonance (MR, n=4 including diffusion and proton magnetic resonance spectroscopy in 1) imaging of 25 patients with pathologically confirmed cerebral hydatid disease. 19 HC were seen in children under 16 years. All were supra tentorial with 22 in the middle cerebral artery territory. HC was solitary in 18 cases, unilocular in 23 and multi-vesicular in 2 with heavily calcified pericyst in 1. 2 cysts were intra ventricular and 1 intra aqueducal. The most typical features were well defined, smooth thin walled spherical or oval cystic lesions of CSF density and/or signal with considerable mass effect (20/25). Surrounding oedema with complete or incomplete rim enhancement was seen in 3 cases which were labelled as complicated and/or infected cysts. Although CT is diagnostic of hydatid disease in almost all cases (22/25), MRI including diffusion and spectroscopy precisely demonstrate location, number, cyst capsule, type of signal and enhancement and allows diagnosis of atypical or complicated HC and appears more helpful in surgical planning.

  15. Pregnancy and Vascular Liver Disease

    PubMed Central

    Bissonnette, Julien; Durand, François; de Raucourt, Emmanuelle; Ceccaldi, Pierre-François; Plessier, Aurélie; Valla, Dominique; Rautou, Pierre-Emmanuel

    2015-01-01

    Vascular disorders of the liver frequently affect women of childbearing age. Pregnancy and the postpartum are prothrombotic states. Pregnancy seems to be a trigger for Budd–Chiari syndrome in patients with an underlying prothrombotic disorder. Whether pregnancy is a risk factor for other vascular liver disorders is unknown. In women with a known vascular liver disorder and a desire for pregnancy, stabilisation of the liver disease, including the use of a portal decompressive procedure when indicated, should be reached prior to conception. The presence of esophageal varices should be screened and adequate prophylaxis of bleeding applied in a manner similar to what is recommended for patients with cirrhosis. Most women likely benefit from anticoagulation during pregnancy and the postpartum. Labor and delivery are best managed by a multidisciplinary team with experience in this situation. Assisted vaginal delivery is the preferred mode of delivery. Although the risk of miscarriage and premature birth is heightened, current management of these diseases makes it very likely to see the birth of a live baby when pregnancy reaches 20 weeks of gestation. PMID:25941432

  16. Pediatric stroke: the importance of cerebral arteriopathy and vascular malformations.

    PubMed

    Beslow, Lauren A; Jordan, Lori C

    2010-10-01

    Population-based estimates of the annual incidence of childhood stroke range from 2 to 13 per 100,000 person-years. More than half of children who have had a stroke have long-term neurological sequelae. The goal of this article is to review recent literature on both hemorrhagic and ischemic stroke in children with a focus on cerebral arteriopathy and vascular malformations as stroke risk factors. Additionally, we review diagnostic studies for childhood stroke, outcome data, and regional and geographic practice differences. PubMed was searched using the terms child, childhood, pediatric, stroke, ischemic, intracerebral hemorrhage, vasculopathy, and vascular malformation. Reference lists of these articles were reviewed for additional key publications. Preference was given to articles published since the year 2000; however, seminal articles in the field were also reviewed. Pediatric stroke is a heterogeneous disorder and a major cause of morbidity in the pediatric population. Five-year recurrence risk is estimated to be 5-19%. Children with cerebrovascular abnormalities are at the highest risk of recurrence (66% at 5 years for ischemic stroke in one study). Furthermore, cerebral arteriopathy including arterial dissection may account for up to 80% of childhood stroke in otherwise healthy children. In many cases, evaluation and treatment of pediatric stroke is not evidence-based, and regional and geographic variations in practice patterns exist. Ultimately multicenter cohort studies and dedicated pediatric clinical trials are essential to establish comprehensive evidence-based guidelines for pediatric stroke care.

  17. Retinal vascular calibers associate differentially with cerebral gray matter and white matter atrophy.

    PubMed

    Ikram, Mohammad K; de Jong, Frank J; Vernooij, Meike W; Hofman, Albert; Niessen, Wiro J; van der Lugt, Aad; Klaver, Caroline C; Ikram, Mohammad A

    2013-01-01

    Cerebral small-vessel disease is thought to contribute to brain atrophy, but it remains unclear whether it affects the gray matter and white matter atrophy differentially. Retinal vessels provide a direct measure to study cerebral small-vessel disease in vivo. In a cohort of 1065 persons (mean age, 67.5 y and 51% women), from the population-based Rotterdam Study, we investigated how retinal vascular calibers relate to brain atrophy and to gray matter and white matter atrophy separately. Retinal arteriolar and venular calibers were semiautomatically measured on digitized fundus transparencies. Using automated quantification of MRI scans, we obtained whole-brain volume and volumes of gray matter and white matter. Both narrower arteriolar and wider venular calibers were associated with smaller brain volume, independent from each other. These associations were primarily driven by smaller white matter volume, whereas no associations were seen for gray matter volume. Adjustments for cardiovascular risk factors attenuated the results, but wider venular caliber remained borderline significantly associated with smaller white matter volume. Our data provide evidence that cerebral small-vessel disease contributes to brain atrophy primarily by affecting the cerebral white matter.

  18. Cerebral Cavernous Malformations: Somatic Mutations in Vascular Endothelial Cells

    PubMed Central

    Gault, Judith; Awad, Issam A.; Recksiek, Peter; Shenkar, Robert; Breeze, Robert; Handler, Michael; Kleinschmidt-DeMasters, Bette Kay

    2009-01-01

    OBJECTIVE Germline mutations in three genes have been found in familial cases of cerebral cavernous malformations (CCM). We previously discovered somatic and germline truncating mutations in the KRIT1 gene supporting the “two-hit” mechanism of CCM lesion formation in a single lesion. The purpose of this study was to screen for somatic, nonheritable, mutations in three more lesions from different patients and identify the cell type(s) in which somatic mutations occur. METHODS Somatic mutations were sought in DNA from three surgically excised, fresh-frozen CCM lesions by cloning and screening PCR products generated from KRIT1 or PDCD10 coding regions. Laser capture microdissection (LCM) was used to isolated endothelial and nonendothelial cells in order to determine if somatic mutations were found in endothelial cells. RESULTS A CCM lesion harbored somatic and germline KRIT1 mutations on different chromosomes and are therefore biallelic. Both mutations are predicted to truncate the protein. The KRIT1 somatic mutations (novel c.1800delG mutation and previously identified 34 nucleotide deletion) in CCMs from two different patients were only found in the vascular endothelial cells lining caverns. No obvious somatic mutations were identified in the two other lesions; however, the results were inconclusive possibly due to the technical limitations or the fact that these specimens had a small proportion of vascular endothelial cells lining pristine caverns. CONCLUSION The “two-hit” mechanism occurs in vascular endothelial cells lining CCM caverns from two patients with somatic and Hispanic-American KRIT1 germline mutations. Methods for somatic mutation detection should focus on vascular endothelial cells lining pristine caverns. PMID:19574835

  19. Cerebral Small Vessel Disease and Arterial Stiffness: Tsunami Effect in the Brain?

    PubMed Central

    Saji, Naoki; Toba, Kenji; Sakurai, Takashi

    2016-01-01

    Background Cerebral small vessel diseases, including silent lacunar infarcts, white matter hyperintensities, and microbleeds, pose a risk for cerebrovascular disease, cognitive impairment, and the geriatric syndrome via effects on arterial stiffness. However, the vascular, physiological, and metabolic roles of arterial stiffness in cerebral small vessel diseases remain unclear. Summary Arterial stiffness can be assessed using various indicators such as the ankle-brachial index, pulse wave velocity, cardio-ankle vascular index, and augmentation index. Arterial stiffness is independently associated with all components of cerebral small vessel disease including silent lacunar infarcts, white matter hyperintensities, and microbleeds, although there are some methodological differences between the various surrogate markers. Evidence of arterial stiffness indicates microvessel arteriosclerosis presenting with vascular endothelial dysfunction. Further, vascular narrowing due to atherosclerosis and vascular stiffness due to lipohyalinosis can accelerate the pulse waves. This hemodynamic stress, pulsatile pressure, or blood pressure variability can cause a ‘tsunami effect’ towards the cerebral parenchyma and lead to cerebral small vessel disease. Previous studies have shown that silent lacunar infarcts and white matter hyperintensities are strongly associated with arterial stiffness. However, the association between microbleeds and arterial stiffness remains controversial, as there are two vessel mechanisms related to microbleeds: cerebral amyloid angiopathy and hypertensive small vessel disease. Key Messages Cerebral small vessel disease with associated arterial stiffness is a risk factor for silent cerebral lesions, stroke, and cognitive impairment. Improvement of the living environment, management of risk factors, and innovation and development of novel drugs that improve arterial stiffness may suppress the progression of cerebral small vessel disease, and may reduce

  20. Vascular pathology: Cause or effect in Alzheimer disease?

    PubMed

    Rius-Pérez, S; Tormos, A M; Pérez, S; Taléns-Visconti, R

    2015-09-15

    Alzheimer disease (AD) is the main cortical neurodegenerative disease. The incidence of this disease increases with age, causing significant medical, social and economic problems, especially in countries with ageing populations. This review aims to highlight existing evidence of how vascular dysfunction may contribute to cognitive impairment in AD, as well as the therapeutic possibilities that might arise from this evidence. The vascular hypothesis emerged as an alternative to the amyloid cascade hypothesis as an explanation for the pathophysiology of AD. This hypothesis locates blood vessels as the origin for a variety of pathogenic pathways that lead to neuronal damage and dementia. Destruction of the organisation of the blood brain barrier, decreased cerebral blood flow, and the establishment of an inflammatory context would thus be responsible for any subsequent neuronal damage since these factors promote aggregation of β-amyloid peptide in the brain. The link between neurodegeneration and vascular dysfunction pathways has provided new drug targets and therapeutic approaches that will add to the treatments for AD. It is difficult to determine whether the vascular component in AD is the cause or the effect of the disease, but there is no doubt that vascular pathology has an important relationship with AD. Vascular dysfunction is likely to act synergistically with neurodegenerative changes in a cycle that exacerbates the cognitive impairment found in AD. Copyright © 2015 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  1. Role of Vascular Risk Factors and Vascular Dysfunction in Alzheimer's Disease

    PubMed Central

    Dickstein, Dara L.; Walsh, Jessica; Brautigam, Hannah; Stockton, Steven D.; Gandy, Samuel; Hof, Patrick R.

    2010-01-01

    Recent findings indicate that vascular risk factors and neurovascular dysfunction play integral roles in the pathogenesis of Alzheimer's disease. In addition to aging, the most common risk factors for Alzheimer's disease are apolipoprotein e4 allele, hypertension, hypotension, diabetes, and hypercholesterolemia. All of these can be characterized by vascular pathology attributed to conditions such as cerebral amyloid angiopathy and subsequent blood-brain barrier dysfunction. Many epidemiological, clinical, and pharmacotherapeutic studies have assessed the associations between such risk factors and Alzheimer's disease and have found positive associations between hypertension, hypotension, and diabetes mellitus. However, there are still many conflicting results from these population-based studies, and they should be interpreted carefully. Recognition of these factors and the mechanisms by which they contribute to Alzheimer's disease will be beneficial in the current treatment regimens for Alzheimer's disease and in the development of future therapies. Here we discuss vascular factors with respect to Alzheimer's disease and dementia and review the factors that give rise to vascular dysfunction and contribute to Alzheimer's disease. PMID:20101718

  2. [A multidisciplinary approach to the management of cerebral vascular malformations].

    PubMed

    Estupiñán, B; López, G; Morales, L; Ochoa, L; García, I; Guerra, E; Zaldivar, M

    Cerebral vascular malformations (CVM) are a heterogeneous group of lesions. One way of classifying them is according to histological criteria, clinical features, imaging findings, electroencephalography and distinctive pathology. To report the results obtained in 16 patients clinically diagnosed as having CVM and operated on in the Centro Internacional de Restauración Neurológica (La Habana, Cuba) between March 1995 and October 1998. We also consider the usefulness of diagnostic tools for neurosurgical management and anatomo-pathological diagnosis. We review the clinical findings, images, electroencephalograms and diagnostic histology of 16 patients. The gender distribution was 10 men and 6 women who were aged between 9 and 48 years. Stereotaxic resection guided by CAT and angiography was done in all cases. The predominant symptoms were headache and generalized tonic-clonic convulsions. CAT and angiography were helpful in determining the clinical diagnosis and location. The most frequent electroencephalographic finding was focal slowing associated with inactive epileptiform disorders. Histological study showed that there were 3 cases of arteriovenous malformations (AVM), one angioma cavernosa and one mixed vascular malformation (AVM plus angioma cavernosa). The malformation was not resected (it was treated with a clip) in the remaining case. Our results show the importance of structural imaging studies and their relationship to functional studies in the presumptive diagnosis of CVM corroborated by post-operative histological diagnosis.

  3. DNA Damage and Repair in Vascular Disease.

    PubMed

    Uryga, Anna; Gray, Kelly; Bennett, Martin

    2016-01-01

    DNA damage affecting both genomic and mitochondrial DNA is present in a variety of both inherited and acquired vascular diseases. Multiple cell types show persistent DNA damage and a range of lesions. In turn, DNA damage activates a variety of DNA repair mechanisms, many of which are activated in vascular disease. Such DNA repair mechanisms either stall the cell cycle to allow repair to occur or trigger apoptosis or cell senescence to prevent propagation of damaged DNA. Recent evidence has indicated that DNA damage occurs early, is progressive, and is sufficient to impair function of cells composing the vascular wall. The consequences of persistent genomic and mitochondrial DNA damage, including inflammation, cell senescence, and apoptosis, are present in vascular disease. DNA damage can thus directly cause vascular disease, opening up new possibilities for both prevention and treatment. We review the evidence for and the causes, types, and consequences of DNA damage in vascular disease.

  4. Protecting against vascular disease in brain

    PubMed Central

    2011-01-01

    Endothelial cells exert an enormous influence on blood vessels throughout the circulation, but their impact is particularly pronounced in the brain. New concepts have emerged recently regarding the role of this cell type and mechanisms that contribute to endothelial dysfunction and vascular disease. Activation of the renin-angiotensin system plays a prominent role in producing these abnormalities. Both oxidative stress and local inflammation are key mechanisms that underlie vascular disease of diverse etiology. Endogenous mechanisms of vascular protection are also present, including antioxidants, anti-inflammatory molecules, and peroxisome proliferator-activated receptor-γ. Despite their clear importance, studies of mechanisms that underlie cerebrovascular disease continue to lag behind studies of vascular biology in general. Identification of endogenous molecules and pathways that protect the vasculature may result in targeted approaches to prevent or slow the progression of vascular disease that causes stroke and contributes to the vascular component of dementia and Alzheimer's disease. PMID:21335467

  5. Genetics of cerebral small vessel disease.

    PubMed

    Choi, Jay Chol

    2015-01-01

    Cerebral small vessel disease (SVD) is an important cause of stroke and cognitive impairment among the elderly and is a more frequent cause of stroke in Asia than in the US or Europe. Although traditional risk factors such as hypertension or diabetes mellitus are important in the development of cerebral SVD, the exact pathogenesis is still uncertain. Both, twin and family history studies suggest heritability of sporadic cerebral SVD, while the candidate gene study and the genome-wide association study (GWAS) are mainly used in genetic research. Robust associations between the candidate genes and occurrence of various features of sporadic cerebral SVD, such as lacunar infarction, intracerebral hemorrhage, or white matter hyperintensities, have not yet been elucidated. GWAS, a relatively new technique, overcomes several shortcomings of previous genetic techniques, enabling the detection of several important genetic loci associated with cerebral SVD. In addition to the more common, sporadic cerebral SVD, several single-gene disorders causing cerebral SVD have been identified. The number of reported cases is increasing as the clinical features become clear and diagnostic examinations are more readily available. These include cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, COL4A1-related cerebral SVD, autosomal dominant retinal vasculopathy with cerebral leukodystrophy, and Fabry disease. These rare single-gene disorders are expected to play a crucial role in our understanding of cerebral SVD pathogenesis by providing animal models for the identification of cellular, molecular, and biochemical changes underlying cerebral small vessel damage.

  6. Genetics of Cerebral Small Vessel Disease

    PubMed Central

    2015-01-01

    Cerebral small vessel disease (SVD) is an important cause of stroke and cognitive impairment among the elderly and is a more frequent cause of stroke in Asia than in the US or Europe. Although traditional risk factors such as hypertension or diabetes mellitus are important in the development of cerebral SVD, the exact pathogenesis is still uncertain. Both, twin and family history studies suggest heritability of sporadic cerebral SVD, while the candidate gene study and the genome-wide association study (GWAS) are mainly used in genetic research. Robust associations between the candidate genes and occurrence of various features of sporadic cerebral SVD, such as lacunar infarction, intracerebral hemorrhage, or white matter hyperintensities, have not yet been elucidated. GWAS, a relatively new technique, overcomes several shortcomings of previous genetic techniques, enabling the detection of several important genetic loci associated with cerebral SVD. In addition to the more common, sporadic cerebral SVD, several single-gene disorders causing cerebral SVD have been identified. The number of reported cases is increasing as the clinical features become clear and diagnostic examinations are more readily available. These include cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, COL4A1-related cerebral SVD, autosomal dominant retinal vasculopathy with cerebral leukodystrophy, and Fabry disease. These rare single-gene disorders are expected to play a crucial role in our understanding of cerebral SVD pathogenesis by providing animal models for the identification of cellular, molecular, and biochemical changes underlying cerebral small vessel damage. PMID:25692103

  7. Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity

    PubMed Central

    Stockton, Rebecca A.; Shenkar, Robert; Awad, Issam A.

    2010-01-01

    Endothelial cell–cell junctions regulate vascular permeability, vasculogenesis, and angiogenesis. Familial cerebral cavernous malformations (CCMs) in humans result from mutations of CCM2 (malcavernin, OSM, MGC4607), PDCD10 (CCM3), or KRIT1 (CCM1), a Rap1 effector which stabilizes endothelial cell–cell junctions. Homozygous loss of KRIT1 or CCM2 produces lethal vascular phenotypes in mice and zebrafish. We report that the physical interaction of KRIT1 and CCM2 proteins is required for endothelial cell–cell junctional localization, and lack of either protein destabilizes barrier function by sustaining activity of RhoA and its effector Rho kinase (ROCK). Protein haploinsufficient Krit1+/− or Ccm2+/− mouse endothelial cells manifested increased monolayer permeability in vitro, and both Krit1+/− and Ccm2+/− mice exhibited increased vascular leak in vivo, reversible by fasudil, a ROCK inhibitor. Furthermore, we show that ROCK hyperactivity occurs in sporadic and familial human CCM endothelium as judged by increased phosphorylation of myosin light chain. These data establish that KRIT1–CCM2 interaction regulates vascular barrier function by suppressing Rho/ROCK signaling and that this pathway is dysregulated in human CCM endothelium, and they suggest that fasudil could ameliorate both CCM disease and vascular leak. PMID:20308363

  8. Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity.

    PubMed

    Stockton, Rebecca A; Shenkar, Robert; Awad, Issam A; Ginsberg, Mark H

    2010-04-12

    Endothelial cell-cell junctions regulate vascular permeability, vasculogenesis, and angiogenesis. Familial cerebral cavernous malformations (CCMs) in humans result from mutations of CCM2 (malcavernin, OSM, MGC4607), PDCD10 (CCM3), or KRIT1 (CCM1), a Rap1 effector which stabilizes endothelial cell-cell junctions. Homozygous loss of KRIT1 or CCM2 produces lethal vascular phenotypes in mice and zebrafish. We report that the physical interaction of KRIT1 and CCM2 proteins is required for endothelial cell-cell junctional localization, and lack of either protein destabilizes barrier function by sustaining activity of RhoA and its effector Rho kinase (ROCK). Protein haploinsufficient Krit1(+/-) or Ccm2(+/-) mouse endothelial cells manifested increased monolayer permeability in vitro, and both Krit1(+/-) and Ccm2(+/-) mice exhibited increased vascular leak in vivo, reversible by fasudil, a ROCK inhibitor. Furthermore, we show that ROCK hyperactivity occurs in sporadic and familial human CCM endothelium as judged by increased phosphorylation of myosin light chain. These data establish that KRIT1-CCM2 interaction regulates vascular barrier function by suppressing Rho/ROCK signaling and that this pathway is dysregulated in human CCM endothelium, and they suggest that fasudil could ameliorate both CCM disease and vascular leak.

  9. A theoretical framework for determining cerebral vascular function and heterogeneity from dynamic susceptibility contrast MRI.

    PubMed

    Digernes, Ingrid; Bjørnerud, Atle; Vatnehol, Svein Are S; Løvland, Grete; Courivaud, Frédéric; Vik-Mo, Einar; Meling, Torstein R; Emblem, Kyrre E

    2017-06-01

    Mapping the complex heterogeneity of vascular tissue in the brain is important for understanding cerebrovascular disease. In this translational study, we build on previous work using vessel architectural imaging (VAI) and present a theoretical framework for determining cerebral vascular function and heterogeneity from dynamic susceptibility contrast magnetic resonance imaging (MRI). Our tissue model covers realistic structural architectures for vessel branching and orientations, as well as a range of hemodynamic scenarios for blood flow, capillary transit times and oxygenation. In a typical image voxel, our findings show that the apparent MRI relaxation rates are independent of the mean vessel orientation and that the vortex area, a VAI-based parameter, is determined by the relative oxygen saturation level and the vessel branching of the tissue. Finally, in both simulated and patient data, we show that the relative distributions of the vortex area parameter as a function of capillary transit times show unique characteristics in normal-appearing white and gray matter tissue, whereas tumour-voxels in comparison display a heterogeneous distribution. Collectively, our study presents a comprehensive framework that may serve as a roadmap for in vivo and per-voxel determination of vascular status and heterogeneity in cerebral tissue.

  10. Demyelinating, degenerative, and vascular disease.

    PubMed

    Dooley, D M

    1977-01-01

    Fifty per cent of patients diagnosed as having multiple sclerosis, primary lateral sclerosis, or hereditary spinocerebellar disorders were observed to have enduring favorable changes in neurological function during the 15 to 27 months they have been followed. The patients who were the least severely disabled were benefitted the most by the stimulation and made the most rapid progress. For example, the patient having only an ataxic or a spastic gait typically was observed to improve faster than the patient having both an ataxic and a spastic gait. The long term effect of electrostimulation of the spinal cord on these patients is unknown. The purpose of the stimulation is to attempt to obtain an improvement in neurological function so that the patient may experience a better life style. It is not thought that the electrical current has any effect on the basic disease process. Electrostimulation over the posterior spinal roots and spinal cord, although not new, has not been used extensively for the treatment of patients with arterial disease. The patients who have responded the most dramatically to electrostimulation are those with vasospastic disorders. A larger percentage of patients showed a greater response to implanted stimulation than to transcutaneous stimulation. Electrostimulation of the nervous system is not designed to replace standard therapeutic measures of treatment of patients with vascular disease, but to supplement them.

  11. Digital Subtraction Angiography In Peripheral Vascular Disease

    NASA Astrophysics Data System (ADS)

    Stieghorst, Michael F.; Crummy, Andrew B.; Lieberman, Robert P.; Turnipseed, William D.; Detmer, Donald E.; Berkoff, Herbert A.

    1981-11-01

    Digital subtraction angiography (DSA) has considerable utility in the evaluation of peripheral vascular disease. It is useful in screening selected patients for vascular disease and its relative ease of performance and good patient tolerance make it ideal for serial examinations of post operative patients. When used in conjunction with intra arterial injections, the technique may show "run-off" vessels which were not demonstrated by standard angiography. This paper presents our experience using DSA to image peripheral vascular problems.

  12. Circulating Vascular Progenitor Cells in Moyamoya Disease

    PubMed Central

    Kang, Hyun-Seung; Wang, Kyu-Chang

    2015-01-01

    Various approaches have been attempted in translational moyamoya disease research. One promising material for modeling and treating this disease is vascular progenitor cells, which can be acquired and expanded from patient peripheral blood. These cells may provide a novel experimental model and enable us to obtain insights regarding moyamoya disease pathogenesis. We briefly present the recent accomplishments in regard to the studies of vascular progenitor cells in moyamoya disease. PMID:26180610

  13. [Impact of premature birth on long term cardio-cerebral vascular events of puerpera].

    PubMed

    Li, Dongqing; Tao, Jie; Dong, Yan; Zhao, Haiyan; Gao, Xinying; Ji, Chunpeng; Wang, Lijiao; Xiang, Honghu; Wu, Shouling

    2014-07-01

    To investigate the impact of premature birth on long term cardio-cerebral vascular events of puerpera. Ambispective cohort study method was used and 3 659 pregnant women giving birth during October 1976 to December 2008 at Kailuan medical group were included and divided into premature birth (PTB) group (n = 226) and non-PTB (NPTB) group (n = 3 433) by the history of PTB. Incidence of cardio-cerebral vascular events (myocardial infarction, cerebral infarction and cerebral hemorrhage) was obtained during follow-up. Multivariable Cox proportional hazards regression models was used to assess the relative risk of cardio-cerebral vascular events. (1) The childbearing age, proportion of pregnancy-induced hypertension, systolic blood pressure and diastolic blood pressure before delivery were significantly higher while weight and height of newborn were significantly less in PTB group than in NPTB group (P < 0.05 or 0.01). (2) There were 71 cardio-cerebral vascular events during the follow-up of (15.19 ± 7.75) years. In PTB group, the incidence of cardio-cerebral vascular events and myocardial infarction was 3.23/1 000 person-years and 2.05/1 000 person-years, respectively, while the corresponding incidence was 1.15/1 000 person-years and 0.42/1 000 person-years, respectively in NPTB group (all P < 0.05). After adjustment for other traditional cardiovascular risk factors, the risk of total cardio-cerebral vascular events, myocardial infarction in PTB group was 2.03 fold (95% CI: 1.02-4.04, P = 0.002) and 3.11 fold (95% CI: 1.18-8.18, P < 0.001) higher than in NPTB group. PTB is an independent risk factor for total cardio-cerebral vascular events, especially myocardial infarction of puerpera.

  14. Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia.

    PubMed

    Duncombe, Jessica; Kitamura, Akihiro; Hase, Yoshiki; Ihara, Masafumi; Kalaria, Raj N; Horsburgh, Karen

    2017-10-01

    Increasing evidence suggests that vascular risk factors contribute to neurodegeneration, cognitive impairment and dementia. While there is considerable overlap between features of vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD), it appears that cerebral hypoperfusion is the common underlying pathophysiological mechanism which is a major contributor to cognitive decline and degenerative processes leading to dementia. Sustained cerebral hypoperfusion is suggested to be the cause of white matter attenuation, a key feature common to both AD and dementia associated with cerebral small vessel disease (SVD). White matter changes increase the risk for stroke, dementia and disability. A major gap has been the lack of mechanistic insights into the evolution and progress of VCID. However, this gap is closing with the recent refinement of rodent models which replicate chronic cerebral hypoperfusion. In this review, we discuss the relevance and advantages of these models in elucidating the pathogenesis of VCID and explore the interplay between hypoperfusion and the deposition of amyloid β (Aβ) protein, as it relates to AD. We use examples of our recent investigations to illustrate the utility of the model in preclinical testing of candidate drugs and lifestyle factors. We propose that the use of such models is necessary for tackling the urgently needed translational gap from preclinical models to clinical treatments. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  15. Livedo reticularis and cerebro-vascular disease

    PubMed Central

    Stephens, W. P.; Ferguson, I. T.

    1982-01-01

    Three cases are described in which extensive livedo reticularis was associated with premature cerebrovascular disease. The patients presented with transient cerebral ischaemic attacks and gradually developed permanent neurological damage with intellectual impairment. The value of detailed neuropsychological testing to identify bilateral cortical abnormalities is demonstrated. CAT scanning may reveal multifocal cerebral infarction. The nature of this condition is not understood. ImagesFig. 1 PMID:7100027

  16. Multiple or mixed cerebral microbleeds and dementia in patients with vascular risk factors.

    PubMed

    Miwa, Kaori; Tanaka, Makiko; Okazaki, Shuhei; Yagita, Yoshiki; Sakaguchi, Manabu; Mochizuki, Hideki; Kitagawa, Kazuo

    2014-08-12

    To investigate whether cerebral microbleeds (CMBs) are independently associated with incident dementia in patients with vascular risk factors. Using data from a Japanese cohort of participants with vascular risk factors in an observational study from 2001, we evaluated the association between CMBs at baseline and incident dementia. Baseline brain MRI was used to determine small-vessel disease (CMBs, lacunar infarcts, and white matter hyperintensities) and brain atrophy. Cox proportional hazards analyses were performed for predictors of dementia adjusting for age, sex, APOE ε4 allele, educational level, baseline Mini-Mental State Examination score, cerebrovascular events, vascular risk factors, and MRI findings. Of the 524 subjects (mean age 68 ± 8.3 years, 57.6% male, 12.8 ± 2.6 years of schooling, 21.6% CMBs), 44 patients with incident dementia (20 Alzheimer disease, 18 vascular dementia, 3 mixed-type, and 3 other) were diagnosed during the median 7.5-year follow-up. In multivariate analysis, the presence of overall CMBs was not associated with an increased risk of incident all-cause dementia (p = 0.15). However, multiple CMBs (≥ 2) or mixed (lobar and deep) CMBs were associated with the increased risk of all-cause dementia, whereas strictly lobar CMBs showed no association with any dementia. Multiple CMBs or mixed CMBs independently showed higher risk of all-cause dementia. Our results reinforce the hypothesis that CMBs exert deleterious effects on dementia incidence, suggesting that this association may be mediated by vascular burden. © 2014 American Academy of Neurology.

  17. Association factor analysis between osteoporosis with cerebral artery disease: The STROBE study.

    PubMed

    Jin, Eun-Sun; Jeong, Je Hoon; Lee, Bora; Im, Soo Bin

    2017-03-01

    The purpose of this study was to determine the clinical association factors between osteoporosis and cerebral artery disease in Korean population. Two hundred nineteen postmenopausal women and men undergoing cerebral computed tomography angiography were enrolled in this study to evaluate the cerebral artery disease by cross-sectional study. Cerebral artery disease was diagnosed if there was narrowing of 50% higher diameter in one or more cerebral vessel artery or presence of vascular calcification. History of osteoporotic fracture was assessed using medical record, and radiographic data such as simple radiography, MRI, and bone scan. Bone mineral density was checked by dual-energy x-ray absorptiometry. We reviewed clinical characteristics in all patients and also performed subgroup analysis for total or extracranial/ intracranial cerebral artery disease group retrospectively. We performed statistical analysis by means of chi-square test or Fisher's exact test for categorical variables and Student's t-test or Wilcoxon's rank sum test for continuous variables. We also used univariate and multivariate logistic regression analyses were conducted to assess the factors associated with the prevalence of cerebral artery disease. A two-tailed p-value of less than 0.05 was considered as statistically significant. All statistical analyses were performed using R (version 3.1.3; The R Foundation for Statistical Computing, Vienna, Austria) and SPSS (version 14.0; SPSS, Inc, Chicago, Ill, USA). Of the 219 patients, 142 had cerebral artery disease. All vertebral fracture was observed in 29 (13.24%) patients. There was significant difference in hip fracture according to the presence or absence of cerebral artery disease. In logistic regression analysis, osteoporotic hip fracture was significantly associated with extracranial cerebral artery disease after adjusting for multiple risk factors. Females with osteoporotic hip fracture were associated with total calcified cerebral artery

  18. The Third, Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial

    ClinicalTrials.gov

    2017-07-05

    Cerebral Hemorrhage; Stroke; Hypertension; Diabetes; Anticoagulant-induced Bleeding; Cerebral Vascular Disorder; Brain Disorder; Hemorrhage; Intracranial Hemorrhages; Cardiovascular Diseases; Central Nervous System Diseases

  19. Sulforaphane activates the cerebral vascular Nrf2-ARE pathway and suppresses inflammation to attenuate cerebral vasospasm in rat with subarachnoid hemorrhage.

    PubMed

    Zhao, Xudong; Wen, Liting; Dong, Min; Lu, Xiaojie

    2016-12-15

    Nrf2-ARE pathway reportedly plays a protective role in several central nervous system diseases. No study has explored the role of the Nrf2-ARE pathway in cerebral vasospasm(CVS) after subarachnoid hemorrhage(SAH). The purpose of the present study was to investigate the activation of the cerebral vascular Nrf2-ARE pathway and to determine the potential role of this pathway in the development of CVS following SAH. We investigated whether the administration of sulforaphane (SFN, a specific Nrf2 activator) modulated vascular caliber, Nrf2-ARE pathway activity, proinflammatory cytokine expression, and clinical behavior in a rat model of SAH. A two-hemorrhage protocol was used to generate an animal model of SAH in male Sprague-Dawley rats. Administration of SFN to these rats following SAH enhanced the activity of the Nrf2-ARE pathway and suppressed the release of proinflammatory cytokines. Vasospasm was markedly attenuated in the basilar arteries after SFN therapy. Additionally, SFN administration significantly ameliorated two behavioral functions disrupted by SAH. These results suggest that SFN has a therapeutic benefit in post-SAH, and this may be due to elevated Nrf2-ARE pathway activity and inhibition of cerebral vascular proinflammatory cytokine expression.

  20. Cerebral Microbleeds in Patients with Dementia with Lewy Bodies and Parkinson Disease Dementia.

    PubMed

    Kim, S W; Chung, S J; Oh, Y-S; Yoon, J H; Sunwoo, M K; Hong, J Y; Kim, J-S; Lee, P H

    2015-09-01

    The burden of amyloid β is greater in patients with dementia with Lewy bodies than in those with Parkinson disease dementia, and an increased amyloid β load is closely related to a higher incidence of cerebral microbleeds. Here, we investigated the prevalence and topography of cerebral microbleeds in patients with dementia with Lewy bodies and those with Parkinson disease dementia to examine whether cerebral microbleeds are more prevalent in patients with dementia with Lewy bodies than in those with Parkinson disease dementia. The study population consisted of 42 patients with dementia with Lewy bodies, 88 patients with Parkinson disease dementia, and 35 controls who underwent brain MR imaging with gradient recalled-echo. Cerebral microbleeds were classified as deep, lobar, or infratentorial. The frequency of cerebral microbleeds was significantly greater in patients with dementia with Lewy bodies (45.2%) than in those with Parkinson disease dementia (26.1%) or in healthy controls (17.1%; P = .017). Lobar cerebral microbleeds were observed more frequently in the dementia with Lewy bodies group (40.5%) than in the Parkinson disease dementia (17%; P = .004) or healthy control (8.6%; P = .001) group, whereas the frequencies of deep and infratentorial cerebral microbleeds did not differ among the 3 groups. Logistic regression analyses revealed that, compared with the healthy control group, the dementia with Lewy bodies group was significantly associated with the presence of lobar cerebral microbleeds after adjusting for age, sex, nonlobar cerebral microbleeds, white matter hyperintensities, and other vascular risk factors (odds ratio, 4.39 [95% CI, 1.27-15.25]). However, compared with the healthy control group, the Parkinson disease dementia group was not significantly associated with lobar cerebral microbleeds. This study showed that patients with dementia with Lewy bodies had a greater burden of cerebral microbleeds and exhibited a lobar predominance of cerebral

  1. Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease.

    PubMed

    Kisler, Kassandra; Nelson, Amy R; Montagne, Axel; Zlokovic, Berislav V

    2017-07-01

    Cerebral blood flow (CBF) regulation is essential for normal brain function. The mammalian brain has evolved a unique mechanism for CBF control known as neurovascular coupling. This mechanism ensures a rapid increase in the rate of CBF and oxygen delivery to activated brain structures. The neurovascular unit is composed of astrocytes, mural vascular smooth muscle cells and pericytes, and endothelia, and regulates neurovascular coupling. This Review article examines the cellular and molecular mechanisms within the neurovascular unit that contribute to CBF control, and neurovascular dysfunction in neurodegenerative disorders such as Alzheimer disease.

  2. mTOR drives cerebral blood flow and memory deficits in LDLR(-/-) mice modeling atherosclerosis and vascular cognitive impairment.

    PubMed

    Jahrling, Jordan B; Lin, Ai-Ling; DeRosa, Nicholas; Hussong, Stacy A; Van Skike, Candice E; Girotti, Milena; Javors, Martin; Zhao, Qingwei; Maslin, Leigh Ann; Asmis, Reto; Galvan, Veronica

    2017-01-01

    We recently showed that mTOR attenuation blocks progression and abrogates established cognitive deficits in Alzheimer's disease (AD) mouse models. These outcomes were associated with the restoration of cerebral blood flow (CBF) and brain vascular density (BVD) resulting from relief of mTOR inhibition of NO release. Recent reports suggested a role of mTOR in atherosclerosis. Because mTOR drives aging and vascular dysfunction is a universal feature of aging, we hypothesized that mTOR may contribute to brain vascular and cognitive dysfunction associated with atherosclerosis. We measured CBF, BVD, cognitive function, markers of inflammation, and parameters of cardiovascular disease in LDLR(-/-) mice fed maintenance or high-fat diet ± rapamycin. Cardiovascular pathologies were proportional to severity of brain vascular dysfunction. Aortic atheromas were reduced, CBF and BVD were restored, and cognitive dysfunction was attenuated potentially through reduction in systemic and brain inflammation following chronic mTOR attenuation. Our studies suggest that mTOR regulates vascular integrity and function and that mTOR attenuation may restore neurovascular function and cardiovascular health. Together with our previous studies in AD models, our data suggest mTOR-driven vascular damage may be a mechanism shared by age-associated neurological diseases. Therefore, mTOR attenuation may have promise for treatment of cognitive impairment in atherosclerosis.

  3. Cerebral small vessel disease and incident parkinsonism

    PubMed Central

    van der Holst, Helena M.; van Uden, Inge W.M.; Tuladhar, Anil M.; de Laat, Karlijn F.; van Norden, Anouk G.W.; Norris, David G.; van Dijk, Ewoud J.; Esselink, Rianne A.J.; Platel, Bram

    2015-01-01

    Objective: To investigate the relation between baseline cerebral small vessel disease (SVD) and the risk of incident parkinsonism using different MRI and diffusion tensor imaging (DTI) measures. Methods: In the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) study, a prospective cohort study, 503 elderly participants with SVD and without parkinsonism were included in 2006. During follow-up (2011–2012), parkinsonism was diagnosed according to UK Brain Bank criteria. Cox regression analysis was used to investigate the association between baseline imaging measures and incident all-cause parkinsonism and vascular parkinsonism (VP). Tract-based spatial statistics analysis was used to identify differences in baseline DTI measures of white matter (WM) tracts between participants with VP and without parkinsonism. Results: Follow-up was available from 501 participants (mean age 65.6 years; mean follow-up duration 5.2 years). Parkinsonism developed in 20 participants; 15 were diagnosed with VP. The 5-year risk of (any) parkinsonism was increased for those with a high white matter hyperintensity (WMH) volume (hazard ratio [HR] 1.8 per SD increase, 95% confidence interval [CI] 1.3–2.4) and a high number of lacunes (HR 1.4 per number increase, 95% CI 1.1–1.8) at baseline. For VP, this risk was also increased by the presence of microbleeds (HR 5.7, 95% CI 1.9–16.8) and a low gray matter volume (HR 0.4 per SD increase, 95% CI 0.2–0.8). Lower fractional anisotropy values in bifrontal WM tracts involved in movement control were observed in participants with VP compared to participants without parkinsonism. Conclusions: SVD at baseline, especially a high WMH volume and a high number of lacunes, is associated with incident parkinsonism. Our findings favor a role of SVD in the etiology of parkinsonism. PMID:26446068

  4. Psoriasis and vascular disease: an unsolved mystery.

    PubMed

    Shelling, Michael L; Federman, Daniel G; Prodanovich, Srdjan; Kirsner, Robert S

    2008-05-01

    Psoriasis is an immune disease most commonly recognized for its skin and joint manifestations. These produce significant physical, social, and psychological distress in affected patients and resultant reductions in their quality of life. As expected, these concerns are vital in providing symptomatic improvement and in selecting an individualized therapy. Yet, the approach in management of these patients is likely to change given the growing body of evidence linking psoriasis and vascular disease. Stemming from an anecdotally described relationship, the association between psoriasis and vascular disease has become a focus of current research to further elucidate the pathophysiology underlying and connecting these two diseases. This article includes a review of the classical cardiovascular risk factors, the atherothrombotic markers, and the environmental stressors associated with psoriasis, as well as a critical review of the observed vascular diseases, the proposed mechanism of atherosclerosis, and the benefits of treatment of psoriasis.

  5. Structure and vascular function of MEKK3–cerebral cavernous malformations 2 complex

    SciTech Connect

    Fisher, Oriana S.; Deng, Hanqiang; Liu, Dou; Zhang, Ya; Wei, Rong; Deng, Yong; Zhang, Fan; Louvi, Angeliki; Turk, Benjamin E.; Boggon, Titus J.; Su, Bing

    2015-08-03

    Cerebral cavernous malformations 2 (CCM2) loss is associated with the familial form of CCM disease. The protein kinase MEKK3 (MAP3K3) is essential for embryonic angiogenesis in mice and interacts physically with CCM2, but how this interaction is mediated and its relevance to cerebral vasculature are unknown. Here we report that Mekk3 plays an intrinsic role in embryonic vascular development. Inducible endothelial Mekk3 knockout in neonatal mice is lethal due to multiple intracranial haemorrhages and brain blood vessels leakage. We discover direct interaction between CCM2 harmonin homology domain (HHD) and the N terminus of MEKK3, and determine a 2.35 Å cocrystal structure. We find Mekk3 deficiency impairs neurovascular integrity, which is partially dependent on Rho–ROCK signalling, and that disruption of MEKK3:CCM2 interaction leads to similar neurovascular leakage. We conclude that CCM2:MEKK3-mediated regulation of Rho signalling is required for maintenance of neurovascular integrity, unravelling a mechanism by which CCM2 loss leads to disease.

  6. Structure and vascular function of MEKK3–cerebral cavernous malformations 2 complex

    PubMed Central

    Fisher, Oriana S.; Deng, Hanqiang; Liu, Dou; Zhang, Ya; Wei, Rong; Deng, Yong; Zhang, Fan; Louvi, Angeliki; Turk, Benjamin E.; Boggon, Titus J.; Su, Bing

    2015-01-01

    Cerebral cavernous malformations 2 (CCM2) loss is associated with the familial form of CCM disease. The protein kinase MEKK3 (MAP3K3) is essential for embryonic angiogenesis in mice and interacts physically with CCM2, but how this interaction is mediated and its relevance to cerebral vasculature are unknown. Here we report that Mekk3 plays an intrinsic role in embryonic vascular development. Inducible endothelial Mekk3 knockout in neonatal mice is lethal due to multiple intracranial haemorrhages and brain blood vessels leakage. We discover direct interaction between CCM2 harmonin homology domain (HHD) and the N terminus of MEKK3, and determine a 2.35 Å cocrystal structure. We find Mekk3 deficiency impairs neurovascular integrity, which is partially dependent on Rho–ROCK signalling, and that disruption of MEKK3:CCM2 interaction leads to similar neurovascular leakage. We conclude that CCM2:MEKK3-mediated regulation of Rho signalling is required for maintenance of neurovascular integrity, unravelling a mechanism by which CCM2 loss leads to disease. PMID:26235885

  7. Cerebral/Peripheral Vascular Reactivity and Neurocognition in Middle-Age Athletes

    PubMed Central

    Tarumi, Takashi; Gonzales, Mitzi M.; Fallow, Bennett; Nualnim, Nantinee; Lee, Jeongseok; Pyron, Martha; Tanaka, Hirofumi; Haley, Andreana P.

    2015-01-01

    Introduction Midlife vascular disease risk is associated with higher incidence of cognitive impairment in late life. Regular aerobic exercise improves vascular function, which in turn may translate into better cognitive function. The purpose of this study was to determine the associations among cardiorespiratory fitness, cerebral and peripheral vascular reactivity, and cognitive function in the sedentary and endurance-trained middle-aged adults. Methods Thirty-two endurance-trained and 27 healthy sedentary participants aged 43–65 years underwent measurements of maximal oxygen uptake (VO2max), neurocognitive assessment, cerebrovascular reactivity to CO2 (CVR), and brachial artery flow-mediated dilation (FMD). Results There were no group differences in age, sex, education level, fasting blood glucose, and blood pressure. Compared with sedentary subjects, endurance-trained athletes demonstrated better cognitive performance on memory (z-score: −0.36±1.11 vs. 0.30±0.76, P<0.01), attention-executive function (z-score: −0.21±0.53 vs. 0.18±0.72, P=0.02), and total cognitive composite scores (z-score: −0.27±0.63 vs. 0.23±0.57, P<0.01). Furthermore, brachial FMD (4.70±2.50 % vs. 7.13±3.09 %, P<0.01) and CVR (4.19±0.71 %/mmHg vs. 4.69±1.06 %/mmHg, P=0.052) were greater in endurance-trained individuals than in the sedentary subjects. Total cognitive composite scores showed a significant positive association with brachial FMD (r = 0.36, P < 0.01) and CVR (r = 0.30, P = 0.03). Finally, when brachial FMD and CVR were entered as covariates, fitness-related group differences in total cognitive composite score were significantly attenuated (all P>0.05). Conclusion Endurance-trained middle-aged adults demonstrated better cognitive performance which may, at least in part, be mediated by their enhanced vascular function, including cerebral and endothelial-dependent vascular reactivity. PMID:26083772

  8. Cerebral perfusion alterations and cerebral amyloid in autosomal dominant Alzheimer disease.

    PubMed

    McDade, Eric; Kim, Albert; James, Jeffrey; Sheu, Lei K; Kuan, Dora Chieh-Hsin; Minhas, Davneet; Gianaros, Peter J; Ikonomovic, Snezana; Lopez, Oscar; Snitz, Beth; Price, Julie; Becker, Jim; Mathis, Chet; Klunk, William

    2014-08-19

    To evaluate alterations in cerebral blood flow (CBF) using arterial spin-labeled MRI in autosomal dominant Alzheimer disease (ADAD) mutation carriers (MCs) in relation to cerebral amyloid and compared with age-matched healthy controls. Recent work has identified alterations in CBF in elderly subjects with mild cognitive impairment and Alzheimer dementia using MRI. However, similar studies are lacking in ADAD. Subjects with ADAD are generally free of significant vascular disease and offer the opportunity to measure CBF early in the pathologic process before significant symptom onset when unique markers might be identified. Fourteen MCs (presenilin-1 and amyloid beta precursor protein) (Clinical Dementia Rating [CDR] 0 = 9, CDR 0.5 = 4, CDR 1 = 1) and 50 controls underwent 3-tesla pulsed arterial spin-labeled MRI. SPM8 was used to test the effect of MC status at the voxel level on CBF before and after controlling for age and CDR. MCs had decreased perfusion in the caudate and inferior striatum bilaterally even after controlling for age and CDR. In MCs, separate areas of decreased CBF were associated with increasing cerebral amyloid and to decreased performance of attention and executive function. Early CBF changes were identified in asymptomatic and mildly symptomatic subjects with ADAD, particularly in the anterior striatum. Furthermore, amyloid deposition was associated with decreased CBF in a number of regions including anterior and posterior cortical areas. Both amyloid and decreased CBF were associated with declines primarily in executive cognitive function. © 2014 American Academy of Neurology.

  9. Cerebral perfusion alterations and cerebral amyloid in autosomal dominant Alzheimer disease

    PubMed Central

    Kim, Albert; James, Jeffrey; Sheu, Lei K.; Kuan, Dora Chieh-Hsin; Minhas, Davneet; Gianaros, Peter J.; Ikonomovic, Snezana; Lopez, Oscar; Snitz, Beth; Price, Julie; Becker, Jim; Mathis, Chet; Klunk, William

    2014-01-01

    Objective: To evaluate alterations in cerebral blood flow (CBF) using arterial spin-labeled MRI in autosomal dominant Alzheimer disease (ADAD) mutation carriers (MCs) in relation to cerebral amyloid and compared with age-matched healthy controls. Background: Recent work has identified alterations in CBF in elderly subjects with mild cognitive impairment and Alzheimer dementia using MRI. However, similar studies are lacking in ADAD. Subjects with ADAD are generally free of significant vascular disease and offer the opportunity to measure CBF early in the pathologic process before significant symptom onset when unique markers might be identified. Methods: Fourteen MCs (presenilin-1 and amyloid beta precursor protein) (Clinical Dementia Rating [CDR] 0 = 9, CDR 0.5 = 4, CDR 1 = 1) and 50 controls underwent 3-tesla pulsed arterial spin-labeled MRI. SPM8 was used to test the effect of MC status at the voxel level on CBF before and after controlling for age and CDR. Results: MCs had decreased perfusion in the caudate and inferior striatum bilaterally even after controlling for age and CDR. In MCs, separate areas of decreased CBF were associated with increasing cerebral amyloid and to decreased performance of attention and executive function. Conclusions: Early CBF changes were identified in asymptomatic and mildly symptomatic subjects with ADAD, particularly in the anterior striatum. Furthermore, amyloid deposition was associated with decreased CBF in a number of regions including anterior and posterior cortical areas. Both amyloid and decreased CBF were associated with declines primarily in executive cognitive function. PMID:25031286

  10. Mechanisms of vascular calcification and associated diseases.

    PubMed

    Marulanda, Juliana; Alqarni, Saleh; Murshed, Monzur

    2014-01-01

    Mineralization of bone and tooth extracellular matrix (ECM) is a physiologic process, while soft tissue mineralization, also known as ectopic mineralization (calcification), is a pathologic condition. Vascular calcification is common in aging and also in a number of genetic and metabolic disorders. The calcific deposits in arteries complicate the prognosis and increase the morbidity in diseases such as atherosclerosis, diabetes and chronic kidney disease (CKD). To completely understand the pathophysiology of these lifethreatening diseases, it is critical to elucidate the molecular mechanisms underlying vascular calcification. Unveiling these mechanisms will eventually identify new therapeutic targets and also improve the management of the associated complications. In the current review, we discussed the common determinants of ECM mineralization, the mechanism of vascular calcification associated with several human diseases and outlined the most common therapeutic approaches to prevent its progression.

  11. Nanomedicine approaches in vascular disease: a review.

    PubMed

    Gupta, Anirban Sen

    2011-12-01

    Nanomedicine approaches have revolutionized the treatment of cancer and vascular diseases, where the limitations of rapid nonspecific clearance, poor biodistribution and harmful side effects associated with direct systemic drug administration can be overcome by packaging the agents within sterically stabilized, long-circulating nanovehicles that can be further surface-modified with ligands to actively target cellular/molecular components of the disease. With significant advancements in genetics, proteomics, cellular and molecular biology and biomaterials engineering, the nanomedicine strategies have become progressively refined regarding the modulation of surface and bulk chemistry of the nanovehicles, control of drug release kinetics, manipulation of nanoconstruct geometry and integration of multiple functionalities on single nanoplatforms. The current review aims to capture the various nanomedicine approaches directed specifically toward vascular diseases during the past two decades. Analysis of the promises and limitations of these approaches will help identify and optimize vascular nanomedicine systems to enhance their efficacy and clinical translation in the future. Nanomedicine-based approaches have had a major impact on the treatment and diagnosis of malignancies and vascular diseases. This review discusses various nanomedicine approaches directed specifically toward vascular diseases during the past two decades, highlighting their advantages, limitations and offering new perspectives on future applications. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. [Impact of isolated diastolic hypertension on new-onset cardiovascular and cerebro-vascular diseases].

    PubMed

    Xing, Fengmei; Dong, Yan; Tao, Jie; Gao, Xinying; Zhou, Jianhui; Chen, Shuohua; Ji, Chunpeng; Yao, Tao; Wu, Shouling

    2014-08-01

    To explore the impact of isolated diastolic hypertension (IDH) on new-onset cardio-cerebral vascular diseases (CVD). This cohort study involved 101 510 participants who were employees of the Kailuan Group-a state-run coal mining company, in 2006 and 2007. Among them, 6 780 subjects were diagnosed with IDH, 35 448 subjects were diagnosed with high-normal blood pressure and 19 460 subjects were diagnosed with normal tension. However, none of them had the history of either cardio-cerebral vascular disease or malignant cancer. Cardio-cerebral vascular events including cerebral infarction, cerebral hemorrhage, acute myocardial infarction were recorded every 6 months during the follow-up (47.1 ± 4.8) period. Multivariable Cox proportional hazards regression models were used to analyze the risk factors of first-ever CVD events. 1) There were 675 CVD events occurred during the follow-up period. The incidence rates of CVD events (1.7% vs. 0.9%), cerebral infarction (1.0% vs. 0.6%) and cerebral hemorrhage (0.4% vs. 0.1%) were significantly higher in IDH group than that in the normal tension group (all P < 0.05). 2) After adjustment for other established CVD risk factors, the hazards ratios became 1.67 (95% CI: 1.28-2.17) for total CVD events and 1.59 (95% CI: 1.12-2.27) for cerebral infarction and 2.67 (95% CI: 1.54-4.65) for cerebral hemorrhage in the IDH group. 3). In stratified analysis on age, after adjustment for other established CVD risk factors, the hazards ratio was 2.22 (95% CI: 1.41-3.50) for cerebral infarction in lower 60 years old group, while the it was 7.27 (95% CI: 2.58-20.42) for cerebral hemorrhage in groups older than 60 years of age. IDH was the independent risk factor for the total cardio-cerebral vascular events, on both cerebral infarction and cerebral hemorrhage. The predicted values of IDH for different CVD events were diverse on different age groups.

  13. Tobacco and vascular disease (image)

    MedlinePlus

    Tobacco use and exposure may cause an acceleration of coronary artery disease and peptic ulcer disease. It is also linked to reproductive disturbances, esophageal reflux, hypertension, fetal illness and death, and ...

  14. Emphysema: an autoimmune vascular disease?

    PubMed

    Voelkel, Norbert; Taraseviciene-Stewart, Laima

    2005-01-01

    We propose that an endogenous maintenance program controls lung cell turnover, apoptosis, and tissue repair, and that emphysema is a manifestation of the breakdown of the lung structure maintenance program. Emphysema can be induced experimentally in rats by three methods: blockade of vascular endothelial growth factor receptors using SU5416, a small molecule-tyrosine kinase inhibitor; methylprednisolone, which activates matrix metalloproteinase-9 and decreases Akt phosphorylation; and antibodies directed against endothelial cells (autoimmune emphysema). SU5416-induced emphysema is associated with lung induction of cytochrome P450 and oxidant stress, and a superoxide dismutase mimetic or N-acetylcysteine prevents this form of emphysema. A broad-spectrum metalloproteinase inhibitor prevents methylprednisolone-induced emphysema and, finally, autoimmune emphysema is associated with increased lung tissue metalloproteinase-9 expression and alveolar septal cell apoptosis. Athymic rats, which lack CD4+ T cells, are protected against autoimmune emphysema, whereas adoptive transfer of CD4+ T cells causes autoimmune emphysema in naive adult rats. It appears that vascular endothelial growth factor and signaling via its receptors plays a central role in the lung structural maintenance program, and oxidative stress, proteolysis, and apoptosis may coincide in the moment of lung cell destruction. Interestingly, the methylprednisolone model illustrates that inflammation is not necessary for the development of emphysema.

  15. Semaphorin3A elevates vascular permeability and contributes to cerebral ischemia-induced brain damage

    PubMed Central

    Hou, Sheng Tao; Nilchi, Ladan; Li, Xuesheng; Gangaraju, Sandhya; Jiang, Susan X.; Aylsworth, Amy; Monette, Robert; Slinn, Jacqueline

    2015-01-01

    Semaphorin 3A (Sema3A) increased significantly in mouse brain following cerebral ischemia. However, the role of Sema3A in stroke brain remains unknown. Our aim was to determine wether Sema3A functions as a vascular permeability factor and contributes to ischemic brain damage. Recombinant Sema3A injected intradermally to mouse skin, or stereotactically into the cerebral cortex, caused dose- and time-dependent increases in vascular permeability, with a degree comparable to that caused by injection of a known vascular permeability factor vascular endothelial growth factor receptors (VEGF). Application of Sema3A to cultured endothelial cells caused disorganization of F-actin stress fibre bundles and increased endothelial monolayer permeability, confirming Sema3A as a permeability factor. Sema3A-mediated F-actin changes in endothelial cells were through binding to the neuropilin2/VEGFR1 receptor complex, which in turn directly activates Mical2, a F-actin modulator. Down-regulation of Mical2, using specific siRNA, alleviated Sema3A-induced F-actin disorganization, cellular morphology changes and endothelial permeability. Importantly, ablation of Sema3A expression, cerebrovascular permeability and brain damage were significantly reduced in response to transient middle cerebral artery occlusion (tMCAO) and in a mouse model of cerebral ischemia/haemorrhagic transformation. Together, these studies demonstrated that Sema3A is a key mediator of cerebrovascular permeability and contributes to brain damage caused by cerebral ischemia. PMID:25601765

  16. Semaphorin3A elevates vascular permeability and contributes to cerebral ischemia-induced brain damage.

    PubMed

    Hou, Sheng Tao; Nilchi, Ladan; Li, Xuesheng; Gangaraju, Sandhya; Jiang, Susan X; Aylsworth, Amy; Monette, Robert; Slinn, Jacqueline

    2015-01-20

    Semaphorin 3A (Sema3A) increased significantly in mouse brain following cerebral ischemia. However, the role of Sema3A in stroke brain remains unknown. Our aim was to determine wether Sema3A functions as a vascular permeability factor and contributes to ischemic brain damage. Recombinant Sema3A injected intradermally to mouse skin, or stereotactically into the cerebral cortex, caused dose- and time-dependent increases in vascular permeability, with a degree comparable to that caused by injection of a known vascular permeability factor vascular endothelial growth factor receptors (VEGF). Application of Sema3A to cultured endothelial cells caused disorganization of F-actin stress fibre bundles and increased endothelial monolayer permeability, confirming Sema3A as a permeability factor. Sema3A-mediated F-actin changes in endothelial cells were through binding to the neuropilin2/VEGFR1 receptor complex, which in turn directly activates Mical2, a F-actin modulator. Down-regulation of Mical2, using specific siRNA, alleviated Sema3A-induced F-actin disorganization, cellular morphology changes and endothelial permeability. Importantly, ablation of Sema3A expression, cerebrovascular permeability and brain damage were significantly reduced in response to transient middle cerebral artery occlusion (tMCAO) and in a mouse model of cerebral ischemia/haemorrhagic transformation. Together, these studies demonstrated that Sema3A is a key mediator of cerebrovascular permeability and contributes to brain damage caused by cerebral ischemia.

  17. Is Vasomotion in Cerebral Arteries Impaired in Alzheimer’s Disease?

    PubMed Central

    Di Marco, Luigi Yuri; Farkas, Eszter; Martin, Chris; Venneri, Annalena; Frangi, Alejandro F.

    2015-01-01

    Abstract A substantial body of evidence supports the hypothesis of a vascular component in the pathogenesis of Alzheimer’s disease (AD). Cerebral hypoperfusion and blood-brain barrier dysfunction have been indicated as key elements of this pathway. Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder, frequent in AD, characterized by the accumulation of amyloid-β (Aβ) peptide in cerebral blood vessel walls. CAA is associated with loss of vascular integrity, resulting in impaired regulation of cerebral circulation, and increased susceptibility to cerebral ischemia, microhemorrhages, and white matter damage. Vasomotion— the spontaneous rhythmic modulation of arterial diameter, typically observed in arteries/arterioles in various vascular beds including the brain— is thought to participate in tissue perfusion and oxygen delivery regulation. Vasomotion is impaired in adverse conditions such as hypoperfusion and hypoxia. The perivascular and glymphatic pathways of Aβ clearance are thought to be driven by the systolic pulse. Vasomotion produces diameter changes of comparable amplitude, however at lower rates, and could contribute to these mechanisms of Aβ clearance. In spite of potential clinical interest, studies addressing cerebral vasomotion in the context of AD/CAA are limited. This study reviews the current literature on vasomotion, and hypothesizes potential paths implicating impaired cerebral vasomotion in AD/CAA. Aβ and oxidative stress cause vascular tone dysregulation through direct effects on vascular cells, and indirect effects mediated by impaired neurovascular coupling. Vascular tone dysregulation is further aggravated by cholinergic deficit and results in depressed cerebrovascular reactivity and (possibly) impaired vasomotion, aggravating regional hypoperfusion and promoting further Aβ and oxidative stress accumulation. PMID:25720414

  18. Induction of hyperhomocysteinemia models vascular dementia by induction of cerebral microhemorrhages and neuroinflammation

    PubMed Central

    Sudduth, Tiffany L; Powell, David K; Smith, Charles D; Greenstein, Abigail; Wilcock, Donna M

    2013-01-01

    Vascular dementia (VaD) is the second leading cause of dementia behind Alzheimer's disease (AD) and is a frequent comorbidity with AD, estimated to occur in as many as 40% of AD patients. The causes of VaD are varied and include chronic cerebral hypoperfusion, microhemorrhages, hemorrhagic infarcts, or ischemic infarcts. We have developed a model of VaD by inducing hyperhomocysteinemia (HHcy) in wild-type mice. By placing wild-type mice on a diet deficient in folate, B6, and B12 and supplemented with excess methionine, we induced a moderate HHcy (plasma level homocysteine 82.93±3.561 μmol). After 11 weeks on the diet, the hyperhomocysteinemic mice showed a spatial memory deficit as assessed by the 2-day radial-arm water maze. Also, magnetic resonance imaging and subsequent histology revealed significant microhemorrhage occurrence. We found neuroinflammation induced in the hyperhomocysteinemic mice as determined by elevated interleukin (IL)-1β, tumor necrosis factor (TNF)α, and IL-6 in brain tissue. Finally, we found increased expression and increased activity of the matrix metalloproteinase 2 (MMP2) and MMP9 systems that are heavily implicated in the pathogenesis of cerebral hemorrhage. Overall, we have developed a dietary model of VaD that will be valuable for studying the pathophysiology of VaD and also for studying the comorbidity of VaD with other dementias and other neurodegenerative disorders. PMID:23361394

  19. Protective or pathogenic effects of vascular endothelial growth factor (VEGF) as potential biomarker in cerebral malaria

    PubMed Central

    Canavese, Miriam; Spaccapelo, Roberta

    2014-01-01

    Cerebral malaria (CM) is the major lethal complication of Plasmodium falciparum infection. It is characterized by persistent coma along with symmetrical motor signs. Several clinical, histopathological, and laboratory studies have suggested that cytoadherence of parasitized erythrocytes, neural injury by malarial toxin, and excessive inflammatory cytokine production are possible pathogenic mechanisms. Although the detailed pathophysiology of CM remains unsolved, it is thought that the binding of parasitized erythrocytes to the cerebral endothelia of microvessels, leading to their occlusion and the consequent angiogenic dysregulation play a key role in the disease pathogenesis. Recent evidences showed that vascular endothelial growth factor (VEGF) and its receptor-related molecules are over-expressed in the brain tissues of CM patients, as well as increased levels of VEGF are detectable in biologic samples from malaria patients. Whether the modulation of VEGF is causative agent of CM mortality or a specific phenotype of patients with susceptibility to fatal CM needs further evaluation. Currently, there is no biological test available to confirm the diagnosis of CM and its complications. It is hoped that development of biomarkers to identify patients and potential risk for adverse outcomes would greatly enhance better intervention and clinical management to improve the outcomes. We review and discuss here what it is currently known in regard to the role of VEGF in CM as well as VEGF as a potential biomarker. PMID:24601908

  20. Cerebral Hemodynamics and Vascular Reactivity in Mild and Severe Ischemic Rodent Middle Cerebral Artery Occlusion Stroke Models

    PubMed Central

    Sim, Jeongeun; Jo, Areum; Kang, Bok-Man; Lee, Sohee; Bang, Oh Young; Heo, Chaejeong; Jhon, Gil-Ja; Lee, Youngmi

    2016-01-01

    Ischemia can cause decreased cerebral neurovascular coupling, leading to a failure in the autoregulation of cerebral blood flow. This study aims to investigate the effect of varying degrees of ischemia on cerebral hemodynamic reactivity using in vivo real-time optical imaging. We utilized direct cortical stimulation to elicit hyper-excitable neuronal activation, which leads to induced hemodynamic changes in both the normal and middle cerebral artery occlusion (MCAO) ischemic stroke groups. Hemodynamic measurements from optical imaging accurately predict the severity of occlusion in mild and severe MCAO animals. There is neither an increase in cerebral blood volume nor in vessel reactivity in the ipsilateral hemisphere (I.H) of animals with severe MCAO. The pial artery in the contralateral hemisphere (C.H) of the severe MCAO group reacted more slowly than both hemispheres in the normal and mild MCAO groups. In addition, the arterial reactivity of the I.H in the mild MCAO animals was faster than the normal animals. Furthermore, artery reactivity is tightly correlated with histological and behavioral results in the MCAO ischemic group. Thus, in vivo optical imaging may offer a simple and useful tool to assess the degree of ischemia and to understand how cerebral hemodynamics and vascular reactivity are affected by ischemia. PMID:27358581

  1. Vascular calcification in chronic kidney disease.

    PubMed

    Jono, Shuichi; Shioi, Atsushi; Ikari, Yuji; Nishizawa, Yoshiki

    2006-01-01

    Vascular calcification is often encountered in advanced atherosclerotic lesions and is a common consequence of aging. Calcification of the coronary arteries has been positively correlated with coronary atherosclerotic plaque burden, increased risk of myocardial infarction, and plaque instability. Chronic kidney disease (CKD) patients have two to five times more coronary artery calcification than healthy age-matched individuals. Vascular calcification is a strong prognostic marker of cardiovascular disease mortality in CKD patients. Vascular calcification has long been considered to be a passive, degenerative, and end-stage process of atherosclerosis and inflammation. However, recent evidence indicates that bone matrix proteins such as osteopontin, matrix Gla protein (MGP), and osteocalcin are expressed in calcified atherosclerotic lesions, and that calcium-regulating hormones such as vitamin D3 and parathyroid hormone-related protein regulate vascular calcification in in vitro vascular calcification models based on cultured aortic smooth muscle cells. These findings suggest that vascular calcification is an actively regulated process similar to osteogenesis, and that bone-associated proteins may be involved in the development of vascular calcification. The pathogenesis of vascular calcification in CKD is not well understood and is almost multifactorial. In CKD patients, several studies have found associations of both traditional risk factors, such as hypertension, hyperlipidemia, and diabetes, and uremic-specific risk factors with vascular calcification. Most patients with progressive CKD develop hyperphosphatemia. An elevated phosphate level is an important risk factor for the development of calcification and cardiovascular mortality in CKD patients. Thus, it is hypothesized that an important regulator of vascular calcification is the level of inorganic phosphate. In order to test this hypothesis, we characterized the response of human smooth muscle cell (HSMC

  2. Vascular radiology in liver disease

    PubMed Central

    Kreel, Louis

    1970-01-01

    Vascular radiology of the liver has increased in scope and function in recent years due mainly to the application of new techniques. It is now possible to examine not only the inferior vena cava and the portal venous system, but also the hepatic veins and the coeliac axis and superior mesenteric artery. Hepatic vein occlusion, portal vein patency and collateral veins, as well as space-occupying lesions, can now be diagnosed with a fair degree of accuracy. These techniques have also helped in the understanding of the altered haemodynamics of portal hypertension and can be used for treatment by intra-arterial perfusion of chemotherapeutic substances. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 14 PMID:5460928

  3. Inhibition of cerebral vascular inflammation by brain endothelium-targeted oligodeoxynucleotide complex.

    PubMed

    Hu, Jing; Al-Waili, Daniah; Hassan, Aishlin; Fan, Guo-Chang; Xin, Mei; Hao, Jiukuan

    2016-08-04

    The present study generated a novel DNA complex to specifically target endothelial NF-κB to inhibit cerebral vascular inflammation. This DNA complex (GS24-NFκB) contains a DNA decoy which inhibits NF-κB activity, and a DNA aptamer (GS-24), a ligand of transferrin receptor (TfR), which allows for targeted delivery of the DNA decoy into cells. The results indicate that GS24-NFκB was successfully delivered into a murine brain-derived endothelial cell line, bEND5, and inhibited inflammatory responses induced by tumor necrosis factor α (TNF-α) or oxygen-glucose deprivation/re-oxygenation (OGD/R) via down-regulation of the nuclear NF-κB subunit, p65, as well as its downstream inflammatory cytokines, inter-cellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1). The inhibitory effect of the GS24-NFκB was demonstrated by a significant reduction in TNF-α or OGD/R induced monocyte adhesion to the bEND5 cells after GS24-NFκB treatment. Intravenous (i.v.) injection of GS24-'NFκB (15mg/kg) was able to inhibit the levels of phoseph-p65 and VCAM-1 in brain endothelial cells in a mouse lipopolysaccharide (LPS)-induced inflammatory model in vivo. In conclusion, our approach using DNA nanotechnology for DNA decoy delivery could potentially be utilized for inhibition of inflammation in ischemic stroke and other neuro-inflammatory diseases affecting cerebral vasculature. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. Homocysteine and non-cardiac vascular disease.

    PubMed

    Katsiki, Niki; Perez-Martinez, Pablo; Mikhailidis, Dimitri P

    2017-03-17

    Elevated homocysteine (Hcy) levels are predictors of cardiovascular disease (CVD). Hyperhomocysteinemia has also been associated with total and CVD mortality. However, whether Hcy is just a marker or plays a causal role in CVD remains to be elucidated. In this narrative review, we discuss the associations between Hcy and non-cardiac vascular diseases, namely stroke, peripheral artery disease (PAD), carotid artery disease, chronic kidney disease (CKD), atherosclerotic renal artery stenosis (ARAS), abdominal aortic aneurysm (AAA) and erectile dysfunction (ED). The effects of several drugs on Hcy levels are also considered. Folic acid, vitamin B6 and B12 supplementation can significantly decrease circulating Hcy concentrations but their effects on CVD risk reduction are conflicting. No current guidelines recommend the routine screening of Hcy levels in patients with non-cardiac vascular diseases. Therefore, further research is needed to elucidate the use of Hcy in the clinical practice.

  5. Lysophosphatidic acid in vascular development and disease.

    PubMed

    Teo, Siew T; Yung, Yun C; Herr, Deron R; Chun, Jerold

    2009-08-01

    Lysophosphatidic acid (LPA) is a small signaling lipid that is capable of stimulating a plethora of different cellular responses through the activation of its family of cognate G protein-coupled receptors. LPA mediates a wide range of biological effects in many tissue types that have been recently reviewed; however, its effects on vasculature development and function have received comparatively less examination. In this review, literature on the actions of LPA in three main aspects of vascular development (vasculogenesis, angiogenesis, and vascular maturation) is discussed. In addition, evidence for the roles of LPA signaling in the formation of secondary vascular structures, such as the blood brain barrier, is considered, consistent with significant roles for LPA signaling in vascular development, function, and disease.

  6. Nanoengineering of therapeutics for retinal vascular disease.

    PubMed

    Gahlaut, Nivriti; Suarez, Sandra; Uddin, Md Imam; Gordon, Andrew Y; Evans, Stephanie M; Jayagopal, Ashwath

    2015-09-01

    Retinal vascular diseases, including diabetic retinopathy, neovascular age related macular degeneration, and retinal vein occlusion, are leading causes of blindness in the Western world. These diseases share several common disease mechanisms, including vascular endothelial growth factor (VEGF) signaling, hypoxia, and inflammation, which provide opportunities for common therapeutic strategies. Treatment of these diseases using laser therapy, anti-VEGF injections, and/or steroids has significantly improved clinical outcomes. However, these strategies do not address the underlying root causes of pathology, and may have deleterious side effects. Furthermore, many patients continue to progress toward legal blindness despite receiving regular therapy. Nanomedicine, the engineering of therapeutics at the 1-100 nm scale, is a promising approach for improving clinical management of retinal vascular diseases. Nanomedicine-based technologies have the potential to revolutionize the treatment of ophthalmology, through enabling sustained release of drugs over several months, reducing side effects due to specific targeting of dysfunctional cells, and interfacing with currently "undruggable" targets. We will discuss emerging nanomedicine-based applications for the treatment of complications associated with retinal vascular diseases, including angiogenesis and inflammation.

  7. Sensory-related neural activity regulates the structure of vascular networks in the cerebral cortex

    PubMed Central

    Lacoste, Baptiste; Comin, Cesar H.; Ben-Zvi, Ayal; Kaeser, Pascal S.; Xu, Xiaoyin; Costa, Luciano da F.; Gu, Chenghua

    2014-01-01

    SUMMARY Neurovascular interactions are essential for proper brain function. While the effect of neural activity on cerebral blood flow has been extensively studied, whether neural activity influences vascular patterning remains elusive. Here, we demonstrate that neural activity promotes the formation of vascular networks in the early postnatal mouse barrel cortex. Using a combination of genetics, imaging, and computational tools to allow simultaneous analysis of neuronal and vascular components, we found that vascular density and branching were decreased in the barrel cortex when sensory input was reduced by either a complete deafferentation, a genetic impairment of neurotransmitter release at thalamocortical synapses, or a selective reduction of sensory-related neural activity by whisker plucking. In contrast, enhancement of neural activity by whisker stimulation led to an increase in vascular density and branching. The finding that neural activity is necessary and sufficient to trigger alterations of vascular networks reveals a novel feature of neurovascular interactions. PMID:25155955

  8. Cerebral Microbleeds, Vascular Risk Factors, and Magnetic Resonance Imaging Markers: The Northern Manhattan Study.

    PubMed

    Caunca, Michelle R; Del Brutto, Victor; Gardener, Hannah; Shah, Nirav; Dequatre-Ponchelle, Nelly; Cheung, Ying Kuen; Elkind, Mitchell S V; Brown, Truman R; Cordonnier, Charlotte; Sacco, Ralph L; Wright, Clinton B

    2016-09-16

    Cerebral microbleeds (CMBs) represent intracerebral hemorrhages due to amyloid angiopathy or exposure to modifiable risk factors. Few community-based stroke-free studies including blacks and Hispanics have been done. The Northern Manhattan Study (NOMAS) is a stroke-free, racially and ethnically diverse cohort study. Brain MRI was performed in 1290 participants, 925 of whom had available T2* gradient-recall echo data. We used multivariable logistic regression to examine the association of sociodemographics, vascular risk factors, apolipoprotein E (APOE) genotype, and brain MRI markers with CMB presence and location. The prevalence of CMBs in our cohort was 5%. Of the 46 participants with CMBs, 37% had only deep CMBs, 48% had only lobar CMBs, and 15% had CMBs in both locations. The difference in CMB distribution was not statistically significant across race/ethnic group or APOE genotype. In multivariable analyses, age (OR [95% CI]: 1.09 [1.04, 1.15]) and SBIs (2.58 [1.01, 6.59]) were positively associated with CMB presence, and diabetes medication use was negatively associated (0.25 [0.07, 0.86]). CMBs may represent the severity of vascular disease in this racially and ethnically diverse cohort. Larger studies are needed to elucidate the association between diabetes medication use and CMB presence. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  9. Critical role of matrix metalloprotease-9 in chronic high fat diet-induced cerebral vascular remodelling and increase of ischaemic brain injury in mice†

    PubMed Central

    Deng, Jiao; Zhang, Junfeng; Feng, Chenzhuo; Xiong, Lize; Zuo, Zhiyi

    2014-01-01

    Aims About one-third of American adults and 20% of teenagers are obese. Obesity and its associated metabolic disturbances including hyperlipidaemia are risk factors for cardiovascular diseases including stroke. They can worsen neurological outcome after stroke. We determined whether obesity and hyperlipidaemia could induce cerebral vascular remodelling via matrix metalloproteases (MMP) and whether this remodelling affected neurological outcome after brain ischaemia. Methods and results Six-week-old male CD1, C57BL/6J, and MMP-9−/− mice were fed regular diet (RD) or high-fat diet (HFD) for 10 weeks. They were subjected to vascular casting or a 90 min middle cerebral arterial occlusion (MCAO). Mice on HFD were heavier and had higher blood glucose and lipid levels than those on RD. HFD-fed CD1 and C57BL/6J mice had an increased cerebral vascular tortuosity index and decreased inner diameters of the middle cerebral arterial root. HFD increased microvessel density in CD1 mouse cerebral cortex. After MCAO, CD1 and C57BL/6J mice on HFD had a bigger infarct volume, more severe brain oedema and blood–brain barrier damage, higher haemorrhagic transformation rate, greater haemorrhagic volume, and worse neurological function. HFD increased MMP-9 activity in the ischaemic and non-ischaemic brain tissues. Although HFD increased the body weights, blood glucose, and lipid levels in the MMP-9−/− mice on a C57BL/6J genetic background, the HFD-induced cerebral vascular remodelling and worsening of neurological outcome did not occur in these mice. Conclusion HFD induces cerebral vascular remodelling and worsens neurological outcome after transient focal brain ischaemia. MMP-9 activation plays a critical role in these HFD effects. PMID:24935427

  10. Antioxidants prevent depletion of [Mg2+]i induced by alcohol in cultured canine cerebral vascular smooth muscle cells: possible relationship to alcohol-induced stroke.

    PubMed

    Li, W; Zheng, T; Altura, B T; Altura, B M

    2001-07-01

    Low serum concentrations of Mg(2+) ions have been reported, recently, in patients with coronary disease, atherosclerosis, and stroke as well as in patients with cerebral hemorrhage. The aim of the present study was to determine whether potent antioxidants [alpha-tocopherol and pyrrolidine dithiocarbamate (PDTC)] can prevent or ameliorate intracellular Mg(2+) ([Mg(2+)](i)) depletion associated with cerebral vascular injury induced by alcohol. Exposure of cultured canine cerebral vascular smooth muscle cells to alcohol (10-100 mM) for 24 h induced marked depletion in [Mg(2+)](i) (i.e., approximately 30-65%, depending upon alcohol concentration). Treatment of the cultured cells with either PDTC (0.1 microM) or alpha-tocopherol (15 microM) for 24 h, alone, failed to interfere with basal [Mg(2+)](i) levels. However, preincubation of the cells with either alpha-tocopherol or PDTC for 24 h completely inhibited the depletion of [Mg(2+)](i) induced by exposure to 10-100 mM ethanol. These results indicate that alpha-tocopherol and PDTC prevent decreases in [Mg(2+)](i) produced by ethanol. Moreover, these new results suggest that such protective effects of alpha-tocopherol and PDTC on cerebral vascular cells might be useful therapeutic tools in prevention and amelioration of cerebral vascular injury and stroke in alcoholics.

  11. Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease

    SciTech Connect

    van Duinen, S.G.; Castano, E.M.; Prelli, F.; Bots, G.T.A.B.; Luyendijk, W.; Frangione, B.

    1987-08-01

    Hereditary cerebral hemorrhage with amyloidosis in Dutch patients is an autosomal dominant form of vascular amyloidosis restricted to the leptomeninges and cerebral cortex. Clinically the disease is characterized by cerebral hemorrhages leading to an early death. Immunohistochemical studies of five patients revealed that the vascular amyloid deposits reacted intensely with an antiserum raised against a synthetic peptide homologous to the Alzheimer disease-related ..beta..-protein. Silver stain-positive, senile plaque-like structures were also labeled by the antiserum, yet these lesions lacked the dense amyloid cores present in typical plaques of Alzheimer disease. No neurofibrillary tangles were present. Amyloid fibrils were purified from the leptomeningeal vessels of one patient who clinically had no signs of dementia. The protein had a molecular weight of approx. 4000 and its partial amino acid sequence to position 21 showed homology to the ..beta..-protein of Alzheimer disease and Down syndrome. These results suggest that hereditary cerebral hemorrhage with amyloidosis of Dutch origin is pathogenetically related to Alzheimer disease and support the concept that the initial amyloid deposition in this disorder occurs in the vessel walls before damaging the brain parenchyma. Thus, deposition of ..beta..-protein in brain tissue seems to be related to a spectrum of diseases involving vascular syndromes, progressive dementia, or both.

  12. Study of the Dynamics of Transcephalic Cerebral Impedance Data during Cardio-Vascular Surgery

    NASA Astrophysics Data System (ADS)

    Atefi, S. R.; Seoane, F.; Lindecrantz, K.

    2013-04-01

    Postoperative neurological deficits are one of the risks associated with cardio vascular surgery, necessitating development of new techniques for cerebral monitoring. In this study an experimental observation regarding the dynamics of transcephalic Electrical Bioimpedance (EBI) in patients undergoing cardiac surgery with and without extracorporeal circulation (ECC) was conducted to investigate the potential use of electrical Bioimpedance for cerebral monitoring in cardio vascular surgery. Tetrapolar transcephalic EBI measurements at single frequency of 50 kHz were recorded prior to and during cardio vascular surgery. The obtained results show that the transcephalic impedance decreases in both groups of patients as operation starts, however slight differences in these two groups were also observed with the cerebral impedance reduction in patients having no ECC being less common and not as pronounced as in the ECC group. Changes in the cerebral impedance were in agreement with changes of haematocrit and temperature. The origin of EBI changes is still unexplained however these results encourage us to continue investigating the application of electrical bioimpedance cerebral monitoring clinically.

  13. Vascular permeability and iron deposition biomarkers in longitudinal follow-up of cerebral cavernous malformations.

    PubMed

    Girard, Romuald; Fam, Maged D; Zeineddine, Hussein A; Tan, Huan; Mikati, Abdul Ghani; Shi, Changbin; Jesselson, Michael; Shenkar, Robert; Wu, Meijing; Cao, Ying; Hobson, Nicholas; Larsson, Henrik B W; Christoforidis, Gregory A; Awad, Issam A

    2016-08-05

    OBJECTIVE Vascular permeability and iron leakage are central features of cerebral cavernous malformation (CCM) pathogenesis. The authors aimed to correlate prospective clinical behavior of CCM lesions with longitudinal changes in biomarkers of dynamic contrast-enhanced quantitative permeability (DCEQP) and quantitative susceptibility mapping (QSM) assessed by MRI. METHODS Forty-six patients with CCMs underwent 2 or more permeability and/or susceptibility studies in conjunction with baseline and follow-up imaging and clinical surveillance during a mean 12.05 months of follow-up (range 2.4-31.27 months). Based on clinical and imaging features, cases/lesions were classified as stable, unstable, or recovering. Associated and predictive changes in quantitative permeability and susceptibility were investigated. RESULTS Lesional mean permeability and QSM values were not significantly different in stable versus unstable lesions at baseline. Mean lesional permeability in unstable CCMs with lesional bleeding or growth increased significantly (+85.9% change; p = 0.005), while mean permeability in stable and recovering lesions did not significantly change. Mean lesional QSM values significantly increased in unstable lesions (+44.1% change; p = 0.01), decreased slightly with statistical significance in stable lesions (-3.2% change; p = 0.003), and did not significantly change in recovering lesions. Familial cases developing new lesions during the follow-up period showed a higher background brain permeability at baseline (p = 0.001), as well as higher regional permeability (p = 0.003) in the area that would later develop a new lesion as compared with the homologous contralateral brain region. CONCLUSIONS In vivo assessment of vascular permeability and iron deposition on MRI can serve as objective and quantifiable biomarkers of disease activity in CCMs. This may be applied in natural history studies and may help calibrate clinical trials. The 2 techniques are likely applicable in

  14. Common Impact of Chronic Kidney Disease and Brain Microhemorrhages on Cerebral Aβ Pathology in SHRSP.

    PubMed

    Pirici, Daniel; Stanaszek, Luiza; Garz, Cornelia; Niklass, Solveig; Heinze, Hans-Jochen; Kalinski, Thomas; Attems, Johannes; Schreiber, Stefanie

    2017-03-01

    While chronic kidney disease seems to be an independent risk factor for cognitive decline, its impact on cerebral amyloid-β (Aβ) depositions, one hallmark of Alzheimer's Disease (AD) pathology, has not been investigated. Utilizing 80 male nontransgenic spontaneously hypertensive stroke prone rats (SHRSP) at various ages (12 to 44 weeks), tubulointerstitial renal damage, prevalence of cerebral microhemorrhages and Aβ accumulations were quantified. Using age-adjusted general linear models we investigated the main and interaction effects of renal damage and cerebral microhemorrhages on cerebral Aβ load. In addition, using post mortem human brain tissue of 16 stroke patients we examined the co-localization of perivascular Aβ deposits and small vessel wall damage. Statistical models revealed an age-independent main effect of tubulointerstitial kidney damage on brain Aβ accumulations, which was reinforced by the consecutive presence of cerebral microhemorrhages. Moreover, cerebral microhemorrhages independently predicted brain Aβ burden in SHRSP. In up to 69% of all human cases perivascular Aβ deposits were detected in the direct vicinity of small vessel wall damage. Our results support the associations between vascular pathology and Aβ deposition, and demonstrate a relationship between chronic kidney disease and cerebral Aβ pathology. Hence, our data suggest that prevention of chronic renal damage may reduce cerebral Aβ pathology. © 2016 International Society of Neuropathology.

  15. Targeting heme oxygenase-1 in vascular disease.

    PubMed

    Durante, William

    2010-12-01

    Heme oxygenase-1 (HO-1) metabolizes heme to generate carbon monoxide (CO), biliverdin, and iron. Biliverdin is subsequently metabolized to bilirubin by biliverdin reductase. HO-1 has recently emerged as a promising therapeutic target in the treatment of vascular disease. Pharmacological induction or gene transfer of HO-1 ameliorates vascular dysfunction in animal models of atherosclerosis, post-angioplasty restenosis, vein graft stenosis, thrombosis, myocardial infarction, and hypertension, while inhibition of HO-1 activity or gene deletion exacerbates these disorders. The vasoprotection afforded by HO-1 is largely attributable to its end products: CO and the bile pigments, biliverdin and bilirubin. These end products exert potent anti-inflammatory, antioxidant, anti-apoptotic, and anti-thrombotic actions. In addition, CO and bile pigments act to preserve vascular homeostasis at sites of arterial injury by influencing the proliferation, migration, and adhesion of vascular smooth muscle cells, endothelial cells, endothelial progenitor cells, or leukocytes. Several strategies are currently being developed to target HO-1 in vascular disease. Pharmacological induction of HO-1 by heme derivatives, dietary antioxidants, or currently available drugs, is a promising near-term approach, while HO-1 gene delivery is a long-term therapeutic goal. Direct administration of CO via inhalation or through the use of CO-releasing molecules and/or CO-sensitizing agents provides an attractive alternative approach in targeting HO-1. Furthermore, delivery of bile pigments, either alone or in combination with CO, presents another avenue for protecting against vascular disease. Since HO-1 and its products are potentially toxic, a major challenge will be to devise clinically effective therapeutic modalities that target HO-1 without causing any adverse effects.

  16. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of white matter lesions on MRI: the evaluation of vascular care in Alzheimer's disease (EVA) study.

    PubMed

    Richard, Edo; Gouw, Alida A; Scheltens, Philip; van Gool, Willem A

    2010-03-01

    White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs and prevents occurrence of new infarcts. A randomized controlled clinical trial, including 123 subjects, compared vascular care with standard care in patients with Alzheimer disease with cerebrovascular lesions on MRI. Progression of WMLs, lacunes, medial temporal lobe atrophy, and global cortical atrophy were semiquantitatively scored after 2-year follow-up. Sixty-five subjects (36 vascular care, 29 standard care) had a baseline and a follow-up MRI and in 58 subjects, a follow-up scan could not be obtained due to advanced dementia or death. Subjects in the vascular care group had less progression of WMLs as measured with the WML change score (1.4 versus 2.3, P=0.03). There was no difference in the number of new lacunes or change in global cortical atrophy or medial temporal lobe atrophy between the 2 groups. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs. Treatment aimed at vascular risk factors in patients with early Alzheimer disease may be beneficial, possibly in an even earlier stage of the disease.

  17. Cerebral blood flow in Alzheimer’s disease

    PubMed Central

    Roher, Alex E; Debbins, Josef P; Malek-Ahmadi, Michael; Chen, Kewei; Pipe, James G; Maze, Sharmeen; Belden, Christine; Maarouf, Chera L; Thiyyagura, Pradeep; Mo, Hua; Hunter, Jesse M; Kokjohn, Tyler A; Walker, Douglas G; Kruchowsky, Jane C; Belohlavek, Marek; Sabbagh, Marwan N; Beach, Thomas G

    2012-01-01

    Background Alzheimer’s disease (AD) dementia is a consequence of heterogeneous and complex interactions of age-related neurodegeneration and vascular-associated pathologies. Evidence has accumulated that there is increased atherosclerosis/arteriosclerosis of the intracranial arteries in AD and that this may be additive or synergistic with respect to the generation of hypoxia/ischemia and cognitive dysfunction. The effectiveness of pharmacologic therapies and lifestyle modification in reducing cardiovascular disease has prompted a reconsideration of the roles that cardiovascular disease and cerebrovascular function play in the pathogenesis of dementia. Methods Using two-dimensional phase-contrast magnetic resonance imaging, we quantified cerebral blood flow within the internal carotid, basilar, and middle cerebral arteries in a group of individuals with mild to moderate AD (n = 8) and compared the results with those from a group of age-matched nondemented control (NDC) subjects (n = 9). Clinical and psychometric testing was performed on all individuals, as well as obtaining their magnetic resonance imaging-based hippocampal volumes. Results Our experiments reveal that total cerebral blood flow was 20% lower in the AD group than in the NDC group, and that these values were directly correlated with pulse pressure and cognitive measures. The AD group had a significantly lower pulse pressure (mean AD 48, mean NDC 71; P = 0.0004). A significant group difference was also observed in their hippocampal volumes. Composite z-scores for clinical, psychometric, hippocampal volume, and hemodynamic data differed between the AD and NDC subjects, with values in the former being significantly lower (t = 12.00, df = 1, P = 0.001) than in the latter. Conclusion These results indicate an association between brain hypoperfusion and the dementia of AD. Cardiovascular disease combined with brain hypoperfusion may participate in the pathogenesis/pathophysiology of neurodegenerative

  18. Correlation of CT cerebral vascular territories with function. 3. Middle cerebral artery

    SciTech Connect

    Berman, S.A.; Hayman, L.A.; Hinck, V.C.

    1984-05-01

    Schematic displays are presented of the cerebral territories supplied by branches of the middle cerebral artery as they would appear on axial and coronal computed tomographic (CT) scan sections. Companion diagrams of regional cortical function and a discussion of the fiber tracts are provided to simplify correlation of clinical deficits with coronal and axial CT abnormalities.

  19. Osteoporosis, osteopenia, and atherosclerotic vascular disease

    PubMed Central

    Aronow, Wilbert S.

    2011-01-01

    Older women with low bone mineral density (BMD) have a higher prevalence of atherosclerotic vascular disease (coronary artery disease, ischemic stroke, or peripheral arterial disease) than older women with normal BMD. Three coronary angiographic studies have shown that low BMD is associated with obstructive coronary artery disease. Low BMD has been shown to be associated with stress test-induced myocardial ischemia, reduced exercise capacity, and with aortic valve calcification. Women with osteoporosis have an increased risk for cardiovascular events. Treatment of osteoporosis or osteopenia should include therapeutic measures to prevent cardiovascular events. PMID:22291728

  20. Selective head cooling during neonatal seizures prevents postictal cerebral vascular dysfunction without reducing epileptiform activity.

    PubMed

    Harsono, Mimily; Pourcyrous, Massroor; Jolly, Elliott J; de Jongh Curry, Amy; Fedinec, Alexander L; Liu, Jianxiong; Basuroy, Shyamali; Zhuang, Daming; Leffler, Charles W; Parfenova, Helena

    2016-11-01

    Epileptic seizures in neonates cause cerebrovascular injury and impairment of cerebral blood flow (CBF) regulation. In the bicuculline model of seizures in newborn pigs, we tested the hypothesis that selective head cooling prevents deleterious effects of seizures on cerebral vascular functions. Preventive or therapeutic ictal head cooling was achieved by placing two head ice packs during the preictal and/or ictal states, respectively, for the ∼2-h period of seizures. Head cooling lowered the brain and core temperatures to 25.6 ± 0.3 and 33.5 ± 0.1°C, respectively. Head cooling had no anticonvulsant effects, as it did not affect the bicuculline-evoked electroencephalogram parameters, including amplitude, duration, spectral power, and spike frequency distribution. Acute and long-term cerebral vascular effects of seizures in the normothermic and head-cooled groups were tested during the immediate (2-4 h) and delayed (48 h) postictal periods. Seizure-induced cerebral vascular injury during the immediate postictal period was detected as terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive staining of cerebral arterioles and a surge of brain-derived circulating endothelial cells in peripheral blood in the normothermic group, but not in the head-cooled groups. During the delayed postictal period, endothelium-dependent cerebral vasodilator responses were greatly reduced in the normothermic group, indicating impaired CBF regulation. Preventive or therapeutic ictal head cooling mitigated the endothelial injury and greatly reduced loss of postictal cerebral vasodilator functions. Overall, head cooling during seizures is a clinically relevant approach to protecting the neonatal brain by preventing cerebrovascular injury and the loss of the endothelium-dependent control of CBF without reducing epileptiform activity. Copyright © 2016 the American Physiological Society.

  1. Cerebral Blood Flow Heterogeneity in Preterm Sheep: Lack of Physiological Support for Vascular Boundary Zones in Fetal Cerebral White Matter

    PubMed Central

    McClure, Melissa; Riddle, Art; Manese, Mario; Luo, Ning Ling; Rorvik, Dawn A.; Kelly, Katherine A.; Barlow, Clyde H.; Kelly, Jeffrey J.; Vinecore, Kevin; Roberts, Colin; Hohimer, A. Roger; Back, Stephen A.

    2011-01-01

    Periventricular white matter (PVWM) injury is the leading cause of chronic neurological disability in survivors of prematurity. To address the role of cerebral ischemia in the pathogenesis of this injury, we tested the hypothesis that immaturity of spatially distal vascular “end” or “border” zones predisposes the PVWM to be more susceptible to falls in cerebral blood flow (CBF) than more proximal regions, such as the cerebral cortex. We used fluorescently-labeled microspheres to quantify regional CBF in situ in the 0.65 gestation fetal sheep in histopathologically-defined 3-dimensional regions by means of post hoc digital dissection and co-registration algorithms. Basal flow in PVWM was significantly lower than gyral white matter and cerebral cortex, but was equivalent in superficial, middle and deep PVWM. Absolute and relative CBF (expressed as percentage of basal) CBF did not differ during ischemia or reperfusion between the PVWM and more superficial gyral white matter or cortex. Moreover, CBF during ischemia and reperfusion was equivalent at three distinct levels of the PVWM. Absolute and relative CBF during ischemia and reperfusion was not predictive of the severity of PVWM injury, as defined by TUNEL staining. However, the magnitude of ischemia to the cerebral cortex directly correlated with lesion severity (r= −0.48, p<.05). Hence, the PVWM did not display unique CBF disturbances that accounted for the distribution of injury. These results suggest that previously-defined cellular-maturational factors have a greater influence on the vulnerability of PVWM to ischemic injury than the presence of immature vascular-boundary zones. PMID:18091757

  2. Vascular wall extracellular matrix proteins and vascular diseases

    PubMed Central

    Xu, Junyan; Shi, Guo-Ping

    2014-01-01

    Extracellular matrix proteins form the basic structure of blood vessels. Along with providing basic structural support to blood vessels, matrix proteins interact with different sets of vascular cells via cell surface integrin or non-integrin receptors. Such interactions induce vascular cell de novo synthesis of new matrix proteins during blood vessel development or remodeling. Under pathological conditions, vascular matrix proteins undergo proteolytic processing, yielding bioactive fragments to influence vascular wall matrix remodeling. Vascular cells also produce alternatively spliced variants that induce vascular cell production of different matrix proteins to interrupt matrix homeostasis, leading to increased blood vessel stiffness; vascular cell migration, proliferation, or death; or vascular wall leakage and rupture. Destruction of vascular matrix proteins leads to vascular cell or blood-borne leukocyte accumulation, proliferation, and neointima formation within the vascular wall; blood vessels prone to uncontrolled enlargement during blood flow diastole; tortuous vein development; and neovascularization from existing pathological tissue microvessels. Here we summarize discoveries related to blood vessel matrix proteins within the past decade from basic and clinical studies in humans and animals — from expression to cross-linking, assembly, and degradation under physiological and vascular pathological conditions, including atherosclerosis, aortic aneurysms, varicose veins, and hypertension. PMID:25045854

  3. Visfatin and cardio-cerebro-vascular disease.

    PubMed

    Wang, Pei; Vanhoutte, Paul M; Miao, Chao-Yu

    2012-01-01

    Nicotinamide phosphoribosyltransferase is the rate-limiting enzyme that catalyzes the first step in the biosynthesis of nicotinamide adenine dinucleotide from nicotinamide. This protein was originally cloned as a putative pre-B cell colony-enhancing factor and also found to be a visceral fat-derived adipokine (visfatin). As a multifunctional protein, visfatin plays an important role in immunity, metabolism, aging, inflammation, and responses to stress. Visfatin also participates in several pathophysiological processes contributing to cardio-cerebro-vascular diseases, including hypertension, atherosclerosis, ischemic heart disease, and ischemic stroke. However, whether visfatin is a friend or a foe in these diseases remains uncertain. This brief review focuses on the current understanding of the complex role of visfatin in the cardio-cerebro-vascular system under normal and pathophysiological conditions.

  4. Mesoglycan: Clinical Evidences for Use in Vascular Diseases

    PubMed Central

    Tufano, Antonella; Arturo, Claudia; Cimino, Ernesto; Di Minno, Matteo Nicola Dario; Di Capua, Mirko; Cerbone, Anna Maria; Di Minno, Giovanni

    2010-01-01

    Vascular glycosaminoglycans (GAG) are essential components of the endothelium and vessel wall and have been shown to be involved in several biologic functions. Mesoglycan, a natural GAG preparation, is a polysaccharide complex rich in sulphur radicals with strong negative electric charge. It is extracted from porcine intestinal mucosa and is composed of heparan sulfate, dermatan sulfate, electrophoretically slow-moving heparin, and variable and minimal quantities of chondroitin sulfate. Data on antithrombotic and profibrinolytic activities of the drug show that mesoglycan, although not indicated in the treatment of acute arterial or venous thrombosis because of the low antithrombotic effect, may be useful in the management of vascular diseases, when combined with antithrombotics in the case of disease of cerebral vasculature, and with antithrombotics and vasodilator drugs in the case of chronic peripheral arterial disease. The protective effect of mesoglycan in patients with venous thrombosis and the absence of side effects, support the use of GAG in patients with chronic venous insufficiency and persistent venous ulcers, in association with compression therapy (zinc bandages, multiple layer bandages, etc.), elastic compression stockings, and local care, and in the prevention of recurrences in patients with previous DVT following the standard course of oral anticoagulation treatment. PMID:21152191

  5. Mesoglycan: clinical evidences for use in vascular diseases.

    PubMed

    Tufano, Antonella; Arturo, Claudia; Cimino, Ernesto; Di Minno, Matteo Nicola Dario; Di Capua, Mirko; Cerbone, Anna Maria; Di Minno, Giovanni

    2010-01-01

    Vascular glycosaminoglycans (GAG) are essential components of the endothelium and vessel wall and have been shown to be involved in several biologic functions. Mesoglycan, a natural GAG preparation, is a polysaccharide complex rich in sulphur radicals with strong negative electric charge. It is extracted from porcine intestinal mucosa and is composed of heparan sulfate, dermatan sulfate, electrophoretically slow-moving heparin, and variable and minimal quantities of chondroitin sulfate. Data on antithrombotic and profibrinolytic activities of the drug show that mesoglycan, although not indicated in the treatment of acute arterial or venous thrombosis because of the low antithrombotic effect, may be useful in the management of vascular diseases, when combined with antithrombotics in the case of disease of cerebral vasculature, and with antithrombotics and vasodilator drugs in the case of chronic peripheral arterial disease. The protective effect of mesoglycan in patients with venous thrombosis and the absence of side effects, support the use of GAG in patients with chronic venous insufficiency and persistent venous ulcers, in association with compression therapy (zinc bandages, multiple layer bandages, etc.), elastic compression stockings, and local care, and in the prevention of recurrences in patients with previous DVT following the standard course of oral anticoagulation treatment.

  6. Cerebral vascular findings in PAPA syndrome: cerebral arterial vasculopathy or vasculitis and a posterior cerebral artery dissecting aneurysm.

    PubMed

    Khatibi, Kasra; Heit, Jeremy J; Telischak, Nicholas A; Elbers, Jorina M; Do, Huy M

    2015-06-24

    A young patient with PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome developed an unusual cerebral arterial vasculopathy/vasculitis (CAV) that resulted in subarachnoid hemorrhage from a ruptured dissecting posterior cerebral artery (PCA) aneurysm. This aneurysm was successfully treated by endovascular coil sacrifice of the affected segment of the PCA. The patient made an excellent recovery with no significant residual neurologic deficit.

  7. Cerebral vascular findings in PAPA syndrome: cerebral arterial vasculopathy or vasculitis and a posterior cerebral artery dissecting aneurysm.

    PubMed

    Khatibi, Kasra; Heit, Jeremy J; Telischak, Nicholas A; Elbers, Jorina M; Do, Huy M

    2016-08-01

    A young patient with PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome developed an unusual cerebral arterial vasculopathy/vasculitis (CAV) that resulted in subarachnoid hemorrhage from a ruptured dissecting posterior cerebral artery (PCA) aneurysm. This aneurysm was successfully treated by endovascular coil sacrifice of the affected segment of the PCA. The patient made an excellent recovery with no significant residual neurologic deficit.

  8. [Celiac disease, cerebral calcifications and epilepsy syndrome].

    PubMed

    Cuvellier, J C; Vallée, L; Nuyts, J P

    1996-10-01

    The syndrome of coeliac disease, epilepsy and cerebral calcifications is a rare complication of coeliac disease. The pathological changes consist in a patchy pial angiomatosis and resemble those of Sturge-Weber syndrome, whose variant without port-wine angioma must be ruled out. Typical course includes three stages leading to a severe encephalopathy. However, the mental impairment is extremely variable. The pathogenetic process is so for unknown; main clues involve a chronic folic acid deficiency or a HLA-related autoimmune disorder. Treatment requires early gluten-free diet and anti-epileptic drug.

  9. Human apolipoprotein E ɛ4 expression impairs cerebral vascularization and blood–brain barrier function in mice

    PubMed Central

    Alata, Wael; Ye, Yue; St-Amour, Isabelle; Vandal, Milène; Calon, Frédéric

    2015-01-01

    Human apolipoprotein E (APOE) exists in three isoforms ɛ2, ɛ3, and ɛ4, of which APOE4 is the main genetic risk factor of Alzheimer's disease (AD). As cerebrovascular defects are associated with AD, we tested whether APOE genotype has an impact on the integrity and function of the blood–brain barrier (BBB) in human APOE-targeted replacement mice. Using the quantitative in situ brain perfusion technique, we first found lower (13.0% and 17.0%) brain transport coefficient (Clup) of [3H]-diazepam in APOE4 mice at 4 and 12 months, compared with APOE2 and APOE3 mice, reflecting a decrease in cerebral vascularization. Accordingly, results from immunohistofluorescence experiments revealed a structurally reduced cerebral vascularization (26% and 38%) and thinner basement membranes (30% and 35%) in 12-month-old APOE4 mice compared with APOE2 and APOE3 mice, suggesting vascular atrophy. In addition, APOE4 mice displayed a 29% reduction in [3H]-d-glucose transport through the BBB compared with APOE2 mice without significant changes in the expression of its transporter GLUT1 in brain capillaries. However, an increase of 41.3% of receptor for advanced glycation end products (RAGE) was found in brain capillaries of 12-month-old APOE4 mice. In conclusion, profound divergences were observed between APOE genotypes at the cerebrovascular interface, suggesting that APOE4-induced BBB anomalies may contribute to AD development. PMID:25335802

  10. Impaired cerebral vascular blood flow in the premature infant.

    PubMed

    Bell, P L; Ellerbee, S

    1993-06-01

    Approximately 40% to 60% of infants born prior to 32 weeks' gestation experience an IVH. The impact of unregulated CBF precipitating an IVH has ramifications far beyond the walls of the neonatal intensive care unit. Infants who survive alterations in CBF may experience impaired neurologic development. Cerebral ischemia can lead to poor articulation, dysphasia, attention deficit, low intelligence quotient, dyspraxia, dyssynergia, spasticity, and short-term memory dysfunction. The neurologic and intellectual development of these premature infants must continue to be a crucial factor in planning their nursing care.

  11. The effect of ASK1 on vascular permeability and edema formation in cerebral ischemia.

    PubMed

    Song, Juhyun; Cheon, So Yeong; Lee, Won Taek; Park, Kyung Ah; Lee, Jong Eun

    2015-01-21

    Apoptosis signal-regulating kinase-1 (ASK1) is the mitogen-activated protein kinase kinase kinase (MAPKKK) and participates in the various central nervous system (CNS) signaling pathways. In cerebral ischemia, vascular permeability in the brain is an important issue because regulation failure of it results in edema formation and blood-brain barrier (BBB) disruption. To determine the role of ASK1 on vascular permeability and edema formation following cerebral ischemia, we first investigated ASK1-related gene expression using microarray analyses of ischemic brain tissue. We then measured protein levels of ASK1 and vascular endothelial growth factor (VEGF) in brain endothelial cells after hypoxia injury. We also examined protein expression of ASK1 and VEGF, edema formation, and morphological alteration through cresyl violet staining in ischemic brain tissue using ASK1-small interference RNA (ASK1-siRNA). Finally, immunohistochemistry was performed to examine VEGF and aquaporin-1 (AQP-1) expression in ischemic brain injury. Based on our findings, we propose that ASK1 is a regulating factor of vascular permeability and edema formation in cerebral ischemia.

  12. The Association of Type 2 Diabetes Mellitus with Cerebral Gray Matter Volume Is Independent of Retinal Vascular Architecture and Retinopathy

    PubMed Central

    Moran, C.; Tapp, R. J.; Hughes, A. D.; Magnussen, C. G.; Blizzard, L.; Phan, T. G.; Beare, R.; Witt, N.; Venn, A.; Münch, G.; Amaratunge, B. C.; Srikanth, V.

    2016-01-01

    It is uncertain whether small vessel disease underlies the relationship between Type 2 Diabetes Mellitus (T2DM) and brain atrophy. We aimed to study whether retinal vascular architecture, as a proxy for cerebral small vessel disease, may modify or mediate the associations of T2DM with brain volumes. In this cross-sectional study using Magnetic Resonance Imaging (MRI) scans and retinal photographs in 451 people with and without T2DM, we measured brain volumes, geometric measures of retinal vascular architecture, clinical retinopathy, and MRI cerebrovascular lesions. There were 270 people with (mean age 67.3 years) and 181 without T2DM (mean age 72.9 years). T2DM was associated with lower gray matter volume (p = 0.008). T2DM was associated with greater arteriolar diameter (p = 0.03) and optimality ratio (p = 0.04), but these associations were attenuated by adjustments for age and sex. Only optimality ratio was associated with lower gray matter volume (p = 0.03). The inclusion of retinal measures in regression models did not attenuate the association of T2DM with gray matter volume. The association of T2DM with lower gray matter volume was independent of retinal vascular architecture and clinical retinopathy. Retinal vascular measures or retinopathy may not be sufficiently sensitive to confirm a microvascular basis for T2DM-related brain atrophy. PMID:27314049

  13. Mediterranean Diet, Alzheimer Disease, and Vascular Mediation

    PubMed Central

    Scarmeas, Nikolaos; Stern, Yaakov; Mayeux, Richard; Luchsinger, Jose A.

    2011-01-01

    Objectives To examine the association between the Mediterranean diet (MeDi) and Alzheimer disease (AD) in a different AD population and to investigate possible mediation by vascular pathways. Design, Setting, Patients, and Main Outcome Measures A case-control study nested within a community-based cohort in New York, NY. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of AD status (194 patients with AD vs 1790 nondemented subjects) in logistic regression models that were adjusted for cohort, age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, smoking, medical comorbidity index, and body mass index (calculated as weight in kilograms divided by height in meters squared). We investigated whether there was attenuation of the association between MeDi and AD when vascular variables (stroke, diabetes mellitus, hypertension, heart disease, lipid levels) were simultaneously introduced in the models (which would constitute evidence of mediation). Results Higher adherence to the MeDi was associated with lower risk for AD (odds ratio, 0.76; 95% confidence interval, 0.67–0.87; P<.001). Compared with subjects in the lowest MeDi tertile, subjects in the middle MeDi tertile had an odds ratio of 0.47 (95% confidence interval, 0.29–0.76) and those at the highest tertile an odds ratio of 0.32 (95% confidence interval, 0.17–0.59) for AD (P for trend <.001). Introduction of the vascular variables in the model did not change the magnitude of the association. Conclusions We note once more that higher adherence to the MeDi is associated with a reduced risk for AD. The association does not seem to be mediated by vascular comorbidity. This could be the result of either other biological mechanisms (oxidative or inflammatory) being implicated or measurement error of the vascular variables. PMID:17030648

  14. Mediterranean diet, Alzheimer disease, and vascular mediation.

    PubMed

    Scarmeas, Nikolaos; Stern, Yaakov; Mayeux, Richard; Luchsinger, Jose A

    2006-12-01

    To examine the association between the Mediterranean diet (MeDi) and Alzheimer disease (AD) in a different AD population and to investigate possible mediation by vascular pathways. Design, Setting, Patients, and A case-control study nested within a community-based cohort in New York, NY. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of AD status (194 patients with AD vs 1790 nondemented subjects) in logistic regression models that were adjusted for cohort, age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, smoking, medical comorbidity index, and body mass index (calculated as weight in kilograms divided by height in meters squared). We investigated whether there was attenuation of the association between MeDi and AD when vascular variables (stroke, diabetes mellitus, hypertension, heart disease, lipid levels) were simultaneously introduced in the models (which would constitute evidence of mediation). Higher adherence to the MeDi was associated with lower risk for AD (odds ratio, 0.76; 95% confidence interval, 0.67-0.87; P<.001). Compared with subjects in the lowest MeDi tertile, subjects in the middle MeDi tertile had an odds ratio of 0.47 (95% confidence interval, 0.29-0.76) and those at the highest tertile an odds ratio of 0.32 (95% confidence interval, 0.17-0.59) for AD (P for trend <.001). Introduction of the vascular variables in the model did not change the magnitude of the association. We note once more that higher adherence to the MeDi is associated with a reduced risk for AD. The association does not seem to be mediated by vascular comorbidity. This could be the result of either other biological mechanisms (oxidative or inflammatory) being implicated or measurement error of the vascular variables.

  15. Associations among cerebral microbleeds, cerebral large-artery diseases and endothelial function.

    PubMed

    Peng, Qing; Huang, Yining; Sun, Wei; Xing, Haiying

    2014-01-01

    Endothelial dysfunction is not only an early stage of atherosclerosis, but also involved in the pathogenesis of cerebral small-vessel diseases. Patients with cerebral microbleeds (CMBs) may have arteriolosclerosis as well as systemic atherosclerosis. However, little is known about the associations among CMBs, atherosclerosis of cerebral large arteries, and endothelial function. Our study aimed to investigate the relationships among them. This was a cross-sectional study. Ninety patients hospitalized in Peking University First Hospital with acute ischemic stroke were enrolled consecutively between November 1, 2007 and January 31, 2008. All subjects underwent transcranial Doppler and carotid color duplex ultrasonography to record the intima-media thickness (IMT) of common carotid artery, carotid plaque, and cerebral artery stenosis. Brain magnetic resonance imaging (MRI) routine sequences and gradient recall-echo T2(*)-weighted imaging were performed to count CMBs with clinical data blindness. Endothelial function was evaluated using flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of the brachial artery. FMD and NMD were examined by an experienced vascular sonographer using a high-resolution ultrasound. Thirty cases (33.3%) had CMBs with counts ranging from 1 to 30. Both FMD ((9.9 ± 4.8)% vs. (15. 2 ± 7.4)%, P = 0.001) and NMD ((13.7 ± 6.1)% vs. (19.0 ± 7.4)%, P = 0.001) were significantly decreased in CMB-positive patients than in CMB-negative patients. No significant relationships were demonstrated between CMBs and intracranial and/or extracranial artery stenosis. The frequencies of CMBs in patients with IMT≥1.0 mm, carotid plaque, and extracranial artery stenosis were 37.5%, 39.4%, and 47.6% respectively, with no significant difference, but much higher than in patients with IMT <1.0 mm (5%, P < 0.05). In Logistic regression analysis, impaired FMD (OR = 5.783, 95% CI 1.652-6.718, P = 0.007) and high pulse pressure (OR = 6.228, 95% CI 1

  16. Cigarette smoking impairs nitric oxide-mediated cerebral blood flow increase: Implications for Alzheimer's disease.

    PubMed

    Toda, Noboru; Okamura, Tomio

    2016-08-01

    Cerebral blood flow is mainly regulated by nitrergic (parasympathetic, postganglionic) nerves and nitric oxide (NO) liberated from endothelial cells in response to shear stress and stretch of vasculature, whereas sympathetic vasoconstrictor control is quite weak. On the other hand, peripheral vascular resistance and blood flow are mainly controlled by adrenergic vasoconstrictor nerves; endothelium-derived NO and nitrergic nerves play some roles as vasodilator factors. Cigarette smoking impairs NO synthesis in cerebral vascular endothelial cells and nitrergic nerves leading to interference with cerebral blood flow and glucose metabolism in the brain. Smoking-induced cerebral hypoperfusion is induced by impairment of synthesis and actions of NO via endothelial nitric oxide synthase (eNOS)/neuronal NOS (nNOS) inhibition and by increased production of oxygen radicals, resulting in decreased actions of NO on vascular smooth muscle. Nicotine acutely and chronically impairs the action of endothelial NO and also inhibits nitrergic nerve function in chronic use. Impaired cerebral blood supply promotes the synthesis of amyloid β that accelerates blood flow decrease. This vicious cycle is thought to be one of the important factors involving in Alzheimer's disease (AD). Quitting smoking is undoubtedly one of the important ways to prevent and delay the genesis or slow the progress of impaired cognitive function and AD. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  17. Vascular amyloidosis impairs the gliovascular unit in a mouse model of Alzheimer’s disease

    PubMed Central

    Kimbrough, Ian F.; Robel, Stefanie

    2015-01-01

    Reduced cerebral blood flow impairs cognitive function and ultimately causes irreparable damage to brain tissue. The gliovascular unit, composed of neural and vascular cells, assures sufficient blood supply to active brain regions. Astrocytes, vascular smooth muscle cells, and pericytes are important players within the gliovascular unit modulating vessel diameters. While the importance of the gliovascular unit and the signals involved in regulating local blood flow to match neuronal activity is now well recognized, surprisingly little is known about this interface in disease. Alzheimer’s disease is associated with reduced cerebral blood flow. Here, we studied how the gliovascular unit is affected in a mouse model of Alzheimer’s disease, using a combination of ex vivo and in vivo imaging approaches. We specifically labelled vascular amyloid in living mice using the dye methoxy-XO4. We elicited vessel responses ex vivo using either pharmacological stimuli or cell-specific calcium uncaging in vascular smooth muscle cells or astrocytes. Multi-photon in vivo imaging through a cranial window allowed us to complement our ex vivo data in the presence of blood flow after label-free optical activation of vascular smooth muscle cells in the intact brain. We found that vascular amyloid deposits separated astrocyte end-feet from the endothelial vessel wall. High-resolution 3D images demonstrated that vascular amyloid developed in ring-like structures around the vessel circumference, essentially forming a rigid cast. Where vascular amyloid was present, stimulation of astrocytes or vascular smooth muscle cells via ex vivo Ca2+ uncaging or in vivo optical activation produced only poor vascular responses. Strikingly, vessel segments that were unaffected by vascular amyloid responded to the same extent as vessels from age-matched control animals. We conclude that while astrocytes can still release vasoactive substances, vascular amyloid deposits render blood vessels rigid and

  18. Kienböck's disease in cerebral palsy.

    PubMed

    Leclercq, C; Xarchas, C

    1998-12-01

    The incidence of Kienböck's disease is known to be higher in cerebral palsy patients, but little has been written on treatment. We report a case of Kienböck's disease in a young man affected by cerebral palsy. A proximal row carpectomy was done, which relieved spasticity at the same time as treating the disease.

  19. Vascular endothelial cells cultured from patients with cerebral or uncomplicated malaria exhibit differential reactivity to TNF

    PubMed Central

    Wassmer, Samuel Crocodile; Moxon, Christopher Alan; Taylor, Terrie; Grau, Georges Emile; Molyneux, Malcolm Edward; Craig, Alister Gordon

    2011-01-01

    Plasmodium falciparum malaria is a major cause of morbidity and mortality in African children, and factors that determine the development of uncomplicated (UM) versus cerebral malaria (CM) are not fully understood. We studied the ex vivo responsiveness of microvascular endothelial cells to pro-inflammatory stimulation and compared the findings between CM and UM patients. In patients with fatal disease we compared the properties of vascular endothelial cells cultured from brain tissue to those cultured from subcutaneous tissue, and found them to be very similar. We then isolated, purified and cultured primary endothelial cells from aspirated subcutaneous tissue of patients with CM (ECCM) or UM (ECUM) and confirmed the identity of the cells before analysis. Upon TNF stimulation in vitro, ECCM displayed a significantly higher capacity to upregulate ICAM-1, VCAM-1 and CD61 and to produce IL-6 and MCP-1 but not RANTES compared with ECUM. The shedding of endothelial microparticles, a recently described parameter of severity in CM, and the cellular level of activated caspase-3 were both significantly greater in ECCM than in ECUM. These data suggest that inter-individual differences in the endothelial inflammatory response to TNF may be an additional factor influencing the clinical course of malaria. PMID:21029292

  20. Determination of Vascular Reactivity of Middle Cerebral Arteries from Stroke and Spinal Cord Injury Animal Models Using Pressure Myography.

    PubMed

    Anwar, Mohammad A; Eid, Ali H

    2016-01-01

    Stroke and other neurovascular derangements are main causes of global death. They, along with spinal cord injuries, are responsible for being the principal cause of disability due to neurological and cognitive problems. These problems then lead to a burden on scarce financial resources and societal care facilities as well as have a profound effect on patients' families. The mechanism of action in these debilitating diseases is complex and unclear. An important component of these problems arises from derangement of blood vessels, such as blockage due to clotting/embolism, endothelial dysfunction, and overreactivity to contractile agents, as well as alteration in endothelial permeability. Moreover, the cerebro-vasculature (large vessels and arterioles) is involved in regulating blood flow by facilitating auto-regulatory processes. Moreover, the anterior (middle cerebral artery and the surrounding region) and posterior (basilar artery and its immediate locality) regions of the brain play a significant role in triggering the pathological progression of ischemic stroke particularly due to inflammatory activity and oxidative stress. Interestingly, modifiable and non-modifiable cardiovascular risk factors are responsible for driving ischemic and hemorrhagic stroke and spinal cord injury. There are different stroke animal models to examine the pathophysiology of middle cerebral and basilar arteries. In this context, arterial myography offers an opportunity to determine the etiology of vascular dysfunction in these diseases. Herein, we describe the technique of pressure myography to examine the reactivity of cerebral vessels to contractile and vasodilator agents and a prelude to stroke and spinal cord injury.

  1. Clinical Scenarios in Chronic Kidney Disease: Vascular Chronic Diseases.

    PubMed

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria

    2016-01-01

    Vascular chronic diseases represent one of the leading causes of end-stage renal disease in incident dialysis patients. B-Mode ultrasound (US) and color Doppler (CD) have a high sensitivity and specificity in the diagnosis of vascular chronic diseases. US and CD should be used to identify subjects in the high risk population who are affected by main renal artery stenosis (RAS) and to identify and characterize patients without RAS who have chronic ischemic nephropathy caused by nephroangiosclerosis and/or atheroembolic disease. The most important CD parameters in the work-up of suspected RAS are increased peak systolic velocity and diastolic velocity, spectral broadening, high renal:aortic ratio and lateralization of renal resistive indexes (RIs). In the absence of direct or indirect signs of RAS, increases in intraparenchymal RIs, associated with systemic atherosclerotic disease, are indicative of microcirculation damage related to nephroangiosclerosis or atheroembolic disease. © 2016 S. Karger AG, Basel.

  2. Cerebral vascular adaptation to pregnancy and its role in the neurological complications of eclampsia

    PubMed Central

    Sweet, Julie G.; Chan, Siu-Lung

    2011-01-01

    The cerebral circulation has a central role in mediating the neurological complications of eclampsia, yet our understanding of how pregnancy and preeclampsia affect this circulation is severely limited. Here, we show that pregnancy causes outward remodeling of penetrating arterioles and increased capillary density in the brain due to activation of peroxisome proliferator-activated receptor-γ (PPARγ), a transcription factor involved in cerebrovascular remodeling and highly activated in pregnancy. Pregnancy-induced PPARγ activation also significantly affected cerebral hemodynamics, decreasing vascular resistance and increasing cerebral blood flow by ∼40% in response to acute hypertension that caused breakthrough of autoregulation. These structural and hemodynamic changes in the brain during pregnancy were associated with substantially increased blood-brain barrier permeability, an effect that could promote passage of damaging proteins into the brain and cause the neurological complications of eclampsia, including seizure. PMID:21071591

  3. Bacterial toxins activation of abbreviated urea cycle in porcine cerebral vascular smooth muscle cells.

    PubMed

    Mishra, Rajesh G; Tseng, Tzu-Ling; Chen, Mei-Fang; Chen, Po-Yi; Lee, Tony J-F

    2016-12-01

    Nitric oxide (NO) overproduction via induction of inducible nitric oxide synthase (iNOS) is implicated in vasodilatory shock in sepsis, leading to septic encephalopathy and accelerating cerebral ischemic injury. An abbreviated urea-cycle (l-citrulline-l-arginine-NO cycle) has been demonstrated in cerebral perivascular nitrergic nerves and endothelial cells but not in normal cerebral vascular smooth muscle cell (CVSMC). This cycle indicates that argininosuccinate synthase (ASS) catalyzes l-citrulline (l-cit) conversion to form argininosuccinate (AS), and subsequent AS cleavage by argininosuccinate lyase (ASL) forms l-arginine (l-arg), the substrate for NO synthesis. The possibility that ASS enzyme in this cycle was induced in the CVSMC in sepsis was examined. Blood-vessel myography technique was used for measuring porcine isolated basilar arterial tone. NO in cultured CVSMC and in condition mediums were estimated by diaminofluorescein (DAF)-induced fluorescence and Griess reaction, respectively. Immunohistochemical and immunoblotting analyses were used to examine iNOS and ASS induction. l-cit and l-arg, which did not relax endothelium-denuded normal basilar arteries precontracted by U-46619, induced significant vasorelaxation with increased NO production in these arteries and the CVSMCs following 6-hour exposure to 20μg/ml lipopolysaccharide (LPS) or lipoteichoic acid (LTA). Pre-treatment with pyrrolidine dithiocarbamate (PDTC) and salicylate (SAL) (NFκB inhibitors), aminoguanidine (AG, an iNOS inhibitor), and nitro-l-arg (NLA, a non-specific NOS inhibitor) blocked NO synthesis in the CVSMC and attenuated l-cit- and l-arg-induced relaxation of LPS- and LTA-treated arteries. Furthermore, immunohistochemical and immunoblotting studies demonstrated that expression of basal iNOS and ASS in the smooth muscle cell of arterial segments denuded of endothelium and the cultured CVSMCs was significantly increased following 6-hour incubation with LPS or LTA. This increased i

  4. [Cerebro-vascular emergencies: cerebral and meningeal hemorrhage].

    PubMed

    Philippon, Jacques

    2002-01-01

    Intracerebral haemorrhage is the most dramatic, even if not the most frequent among cerebrovascular emergencies. However the improved treatment of arterial hypertension has decreased its frequency. Modern neuroradiological methods have led to an easier diagnosis, but the best choice for treatment (medical or surgical) is still debated. Decision must be based upon different factors, the most important of which are clinical condition volume, and location of haemorrhage. If the general prognosis has been improved by the transfer to specialized Units, wherein such are available, the benefit of surgery, while indispensable in some cases, has yet to be demonstrated by prospective studies. The problem is far different in subarachnoïd haemorrhage due to rupture of a vascular malformation: the necessity of a rapid treatment by surgery or embolization is largely admitted except for those patients in a bad clinical conditions.

  5. Both acute and prolonged administration of EPO reduce cerebral and systemic vascular conductance in humans.

    PubMed

    Rasmussen, Peter; Kim, Yu-Sok; Krogh-Madsen, Rikke; Lundby, Carsten; Olsen, Niels V; Secher, Niels H; van Lieshout, Johannes J

    2012-03-01

    Administration of erythropoietin (EPO) has been linked to cerebrovascular events. EPO reduces vascular conductance, possibly because of the increase in hematocrit. Whether EPO in itself affects the vasculature remains unknown; here it was evaluated in healthy males by determining systemic and cerebrovascular variables following acute (30,000 IU/d for 3 d; n=8) and chronic (5000 IU/week for 13 wk; n=8) administration of EPO, while the responsiveness of the vasculature was challenged during cycling exercise, with and without hypoxia. Prolonged administration of EPO increased hematocrit from 42.5 ± 3.7 to 47.6 ± 4.1% (P<0.01), whereas hematocrit was unaffected following acute EPO administration. Yet, the two EPO regimes increased arterial pressure similarly (by 8±4 and 7±3 mmHg, respectively; P=0.01) through reduced vascular conductance (by 7±3 and 5±2%; P<0.05). Also, both EPO regimes widened the arterial-to-jugular O(2) differences at rest as well as during normoxic and hypoxic exercise (P<0.01), which indicated reduced cerebral blood flow despite preserved dynamic cerebral autoregulation, and an increase in middle cerebral artery mean blood flow velocity (P<0.05), therefore, reflected vasoconstriction. Thus, administration of EPO to healthy humans lowers systemic and cerebral conductance independent of its effect on hematocrit.

  6. Role of endovascular embolization for trigeminal neuralgia related to cerebral vascular malformation.

    PubMed

    Ge, Huijian; Lv, Xianli; Jin, Hengwei; He, Hongwei; Li, Youxiang

    2016-10-01

    The objective of this article is to describe the trigeminal neuralgia related to cerebral vascular malformation that is rarely reported and the experience referring to endovascular treatment. A total of 10 patients who had cerebral vascular malformation (AVM and dAVF) in a single center presented with trigeminal neuralgia. Clinical and angiographic presentations as well as their clinical outcomes after embolization were reviewed. Of the 10 cases, seven dAVFs and three AVMs were detected. In contrast to the dilated feeding arteries, an ectasia of the draining vein that is adjacent to the root entry zone of the trigeminal nerve such as the petrosal vein and lateral mesencephalic vein has the major role in causing the trigeminal neuralgia. All of these patients had relief of facial pain after endovascular embolization during follow-up (mean 57.3 months, range 5 to 100 months). There were no permanent neurological deficits. Endovascular embolization is an effective method in treating trigeminal neuralgia related to cerebral vascular malformation. © The Author(s) 2016.

  7. [The family: the support for the elderly with cerebral-vascular accident].

    PubMed

    Guimarães Andrade, Oséias; Partezani Rodríguez, Rosalina Aparecida

    2005-12-01

    This project had these objectives: 1) understand the reality of the family care system for an elderly person suffering from cerebral-vascular accident (CVA), 2) implement an aid to the family care system for an elderly person suffering from cerebral-vascular accident (CVA) from a holistic perspective on health. The sample for this investigation was composed by five families which were intentionally selected, with whom the authors shared the care of an elderly person suffering from CVA in their homes over a six month period. Based on concepts having a holistic reference about health formulated by Capra, the authors drew up the development of a methodology for research and action which has a participatory observation and a Drawing-Record procedural technique for the production of data. These data were subjected to a thematic analysis which made it possible to identify three main themes: 1) the main caretaker as the focus of the family care system; 2) the family care system as a context which has complexities and singularities, 3) the holistic nature of the family care system for an eldely person suffering from cerebral-vascular accident (CVA).

  8. Ryanodine receptors, calcium signaling and regulation of vascular tone in the cerebral parenchymal microcirculation

    PubMed Central

    Dabertrand, Fabrice; Nelson, Mark T.; Brayden, Joseph E.

    2012-01-01

    The cerebral blood supply is delivered by a surface network of pial arteries and arterioles from which arise (parenchymal) arterioles that penetrate into the cortex and terminate in a rich capillary bed. The critical regulation of cerebral blood flow, locally and globally, requires precise vasomotor regulation of the intracerebral microvasculature. This vascular region is anatomically unique as illustrated by the presence of astrocytic processes that envelope almost the entire basolateral surface of parenchymal arterioles. There are, moreover, notable functional differences between pial arteries and parenchymal arterioles. For example, in pial vascular smooth muscle cells (VSMCs), local calcium release events (“calcium sparks”) through ryanodine receptor (RyR) channels in sarcoplasmic reticulum membrane activate large conductance, calcium-sensitive potassium (BK) channels to modulate vascular diameter. In contrast, VSMCs in parenchymal arterioles express functional RyR and BK channels, but under physiological conditions these channels do not oppose pressure-induced vasoconstriction. Here we summarize the roles of ryanodine receptors in the parenchymal microvasculature under physiologic and pathologic conditions, and discuss their importance in the control of cerebral blood flow. PMID:23216877

  9. Small white matter lesion detection in cerebral small vessel disease

    NASA Astrophysics Data System (ADS)

    Ghafoorian, Mohsen; Karssemeijer, Nico; van Uden, Inge; de Leeuw, Frank E.; Heskes, Tom; Marchiori, Elena; Platel, Bram

    2015-03-01

    Cerebral small vessel disease (SVD) is a common finding on magnetic resonance images of elderly people. White matter lesions (WML) are important markers for not only the small vessel disease, but also neuro-degenerative diseases including multiple sclerosis, Alzheimer's disease and vascular dementia. Volumetric measurements such as the "total lesion load", have been studied and related to these diseases. With respect to SVD we conjecture that small lesions are important, as they have been observed to grow over time and they form the majority of lesions in number. To study these small lesions they need to be annotated, which is a complex and time-consuming task. Existing (semi) automatic methods have been aimed at volumetric measurements and large lesions, and are not suitable for the detection of small lesions. In this research we established a supervised voxel classification CAD system, optimized and trained to exclusively detect small WMLs. To achieve this, several preprocessing steps were taken, which included a robust standardization of subject intensities to reduce inter-subject intensity variability as much as possible. A number of features that were found to be well identifying small lesions were calculated including multimodal intensities, tissue probabilities, several features for accurate location description, a number of second order derivative features as well as multi-scale annular filter for blobness detection. Only small lesions were used to learn the target concept via Adaboost using random forests as its basic classifiers. Finally the results were evaluated using Free-response receiver operating characteristic.

  10. The arterial circle of Willis of the mouse helps to decipher secrets of cerebral vascular accidents in the human.

    PubMed

    Okuyama, Shinichi; Okuyama, Jun; Okuyama, Junko; Tamatsu, Yuichi; Shimada, Kazuyuki; Hoshi, Hajime; Iwai, Junichi

    2004-01-01

    The human brain represents an elaborate product of hominizing evolution. Likewise, its supporting vasculature may also embody evolutionary consequences. Thus, it is conceivable that the human tendency to develop cerebral vascular accidents (CVAs) might represent a disease of hominization. In a search for hominizing changes on the arterial circle of Willis (hWAC), we attempted an anatomical comparison of the hWAC with that of the mouse (mWAC) by injecting aliquots of resin into the vasculature of the mouse and then creating vascular endocasts of the mWAC. The internal carotid artery of the mouse (mICA) unites with the mWAC midway between the middle cerebral artery (mMCA) and posterior cerebral artery (mPCA). The mWAC does not complete a circle: the mWAC nourishes the anterior portion of the circle which branches out to the olfactory artery (OlfA) and mPCA, along with the mMCA, and the basilar artery (mBA) does not connect to the mPCA. The OlfA is thicker than the mMCA. The relative brain weight of the mouse was 74 g on average for a 60 kg male and 86 g for a 60 kg female, respectively, as compared with 1424 g for a 60 kg man. These findings are consistent with the mouse being a nocturnal carnivore that lives on olfactory information in contrast to the human that lives diurnally and depends on visual and auditory information. In man, the human ICA (hICA) unites with the hWAC at a point where the human middle cerebral artery (hMCA) branches out, and thus, blood from the hICA does not flow through the hWAC but drains into the hMCA directly. The hMCA is thicker than the anterior cerebral artery. The hPCA receives blood from the hBA rather than from the hICA, and thus, the entire hWAC forms a closed circuit. Since the hICA drains directly into the hMCA without flowing a distance through the hWAC, the capacitor and equalizer functions of the WAC will be mitigated so much that the resultant hemodynamic changes would render the hMCA more likely to contribute to CVAs. Thus

  11. Occludin is overexpressed in Alzheimer's disease and vascular dementia

    PubMed Central

    Romanitan, Mihaela Oana; Popescu, Bogdan O; Winblad, Bengt; Bajenaru, Ovidiu Alexandru; Bogdanovic, Nenad

    2007-01-01

    Abstract The tight junctions (TJs) are key players in the control of blood-brain barrier (BBB) properties, the most complex TJs in the vascular system being found in the endothelial cells of brain capillaries. One of the main TJs proteins is occludin, which anchors plasma membranes of neighbour cells and is present in large amounts in the brain endothelia. Previous studies demonstrated that disruption of BBB in various pathological situations associates with changes in occludin expression, and this change could be responsible for malfunction of BBB. Therefore in this study, applying an immunohistochemical approach, we decided to explore the occludin expression in frontal cortex (FC) and basal ganglia in ageing control, Alzheimer's disease (AD), and vascular dementia (VD) brains, as far as all these pathologies associate microangiopathy and disruption of BBB. Strikingly, we found selected neurons, astrocytes and oligodendrocytes expressing occludin, in all cases studied. To estimate the number of occludin-expressing neurons, we applied a stereological approach with random systematic sampling and the unbiased optical fractionator method. We report here a significant increase in ratio of occludin-expressing neurons in FC and basal ganglia regions in both AD and VD as compared to ageing controls. Within the cerebral cortex, occludin was selectively expressed by pyramidal neurons, which are the ones responsible for cognitive processes and affected by AD pathology. Our findings could be important in unravelling new pathogenic pathways in dementia disorders and new functions of occludin and TJs. PMID:17635647

  12. Magnetic Resonance Imaging of Plaque Burden in Vascular Walls of the Middle Cerebral Artery Correlates with Cerebral Infarction.

    PubMed

    Li, Fei; Chen, Qian-Xue; Chen, Zhi-Biao; Tian, Dao-Feng; Cai, Qiang

    2016-01-01

    Intracranial atherosclerosis may be related to the risk of ischemic stroke. High-resolution magnetic resonance imaging (H-R MRI) makes it possible to measure the intracranial atheroma in vivo. The aim of this study was to evaluate the plaque burden of the middle cerebral artery (MCA) using H-R MRI, and to determine its relationship with both cerebral infarction size and plaque burden in the carotid artery (CA). 54 patients with MCA territory infarction were enrolled and HR-MRI was performed within 7 days following stroke onset. The lumen area (LA), wall area (WA), total vessel area (TVA), and the normalized wall index (NWI) of MCA and CA were measured. We analyzed the status of MCA and CA atheroma, and the size of cerebral infarction, in the corresponding vascular territory. We observed a significant positive correlation between the NWI of the index artery and the volume of the ipsilateral ischemic lesions. In addition, the mean NWI of MCA was significantly correlated with that of the ipsilateral CA (left, r = 0.88, P.0.001; right, r = 0.79, P.0.001), and the plaque burden of the M1 segment of MCA was significantly higher than that of the ipsilateral CA (P < 0.05). There was no significant correlation between the TVA and WA of MCA and that of CA. Our findings suggest that MCA atherosclerosis is significantly correlated with cerebral infarction. In ischemic stroke patients, the plaque burden of M1 segment of MCA is more significant than that of CA.

  13. Discovery of a ROCK inhibitor, FPND, which prevents cerebral hemorrhage through maintaining vascular integrity by interference with VE-cadherin

    PubMed Central

    Li, Shang; Ai, Nana; Shen, Mingyun; Dang, Yuanye; Chong, Cheong-Meng; Pan, Peichen; Kwan, Yiu Wa; Chan, Shun Wan; Leung, George Pak Heng; Hoi, Maggie Pui Man; Hou, Tingjun; Lee, Simon Ming-Yuen

    2017-01-01

    Hemorrhagic stroke occurs when a weakened vessel ruptures and bleeds into the surrounding brain, leading to high rates of death and disability worldwide. A series of complex pathophysiological cascades contribute to the risk of hemorrhagic stroke, and no therapies have proven effective to prevent hemorrhagic stroke. Stabilization of vascular integrity has been considered as a potential therapeutic target for hemorrhagic stroke. ROCKs, which belong to the serine/threonine protein kinase family and participate in the organization of actin cytoskeleton, have become attractive targets for the treatment of strokes. In this study, in vitro enzyme-based assays revealed that a new compound (FPND) with a novel scaffold identified by docking-based virtual screening could inhibit ROCK1 specifically at low micromolar concentration. Molecular modeling showed that FPND preferentially interacted with ROCK1, and the difference between the binding affinity of FPND toward ROCK1 and ROCK2 primarily resulted from non-polar contributions. Furthermore, FPND significantly prevented statin-induced cerebral hemorrhage in a zebrafish model. In addition, in vitro studies using the xCELLigence RTCA system, immunofluorescence and western blotting revealed that FPND prevented statin-induced cerebral hemorrhage by enhancing endothelial cell–cell junctions through inhibiting the ROCK-mediated VE-cadherin signaling pathway. As indicated by the extremely low toxicity of FPND against mice, it is safe and can potentially prevent vascular integrity loss-related diseases, such as hemorrhagic stroke. PMID:28845297

  14. Discovery of a ROCK inhibitor, FPND, which prevents cerebral hemorrhage through maintaining vascular integrity by interference with VE-cadherin.

    PubMed

    Li, Shang; Ai, Nana; Shen, Mingyun; Dang, Yuanye; Chong, Cheong-Meng; Pan, Peichen; Kwan, Yiu Wa; Chan, Shun Wan; Leung, George Pak Heng; Hoi, Maggie Pui Man; Hou, Tingjun; Lee, Simon Ming-Yuen

    2017-01-01

    Hemorrhagic stroke occurs when a weakened vessel ruptures and bleeds into the surrounding brain, leading to high rates of death and disability worldwide. A series of complex pathophysiological cascades contribute to the risk of hemorrhagic stroke, and no therapies have proven effective to prevent hemorrhagic stroke. Stabilization of vascular integrity has been considered as a potential therapeutic target for hemorrhagic stroke. ROCKs, which belong to the serine/threonine protein kinase family and participate in the organization of actin cytoskeleton, have become attractive targets for the treatment of strokes. In this study, in vitro enzyme-based assays revealed that a new compound (FPND) with a novel scaffold identified by docking-based virtual screening could inhibit ROCK1 specifically at low micromolar concentration. Molecular modeling showed that FPND preferentially interacted with ROCK1, and the difference between the binding affinity of FPND toward ROCK1 and ROCK2 primarily resulted from non-polar contributions. Furthermore, FPND significantly prevented statin-induced cerebral hemorrhage in a zebrafish model. In addition, in vitro studies using the xCELLigence RTCA system, immunofluorescence and western blotting revealed that FPND prevented statin-induced cerebral hemorrhage by enhancing endothelial cell-cell junctions through inhibiting the ROCK-mediated VE-cadherin signaling pathway. As indicated by the extremely low toxicity of FPND against mice, it is safe and can potentially prevent vascular integrity loss-related diseases, such as hemorrhagic stroke.

  15. Characterization of cerebral microbleeds in idiopathic Parkinson's disease.

    PubMed

    Kim, J-H; Park, J; Kim, Y-H; Ma, H-I; Kim, Y J

    2015-02-01

    Cerebral microbleeds (CMBs) have been extensively studied in healthy controls and patients with cerebrovascular disease and Alzheimer's disease. Our aim was to characterize the clinical and radiological features of CMBs in idiopathic Parkinson's disease (IPD). This cross-sectional study included consecutive parkinsonian patients who attended the authors' movement disorders clinic from March 2010 to February 2012 and underwent a standard magnetic resonance imaging (MRI) protocol with gradient recalled echo taken with a 3 T MRI machine. Amongst parkinsonian disorders, CMBs were most common in vascular parkinsonism (VP) (56%) and least common in IPD (17.7%). In IPD, CMBs were significantly associated with white matter hyperintensities and concurrent lacunar infarctions. The presence of CMBs had no effect on various cognitive domains in IPD. IPD with CMBs was discriminated from VP by clinical and neuroimaging findings: frequencies of motor subtypes were similar between IPD with and without CMBs, whereas all VP patients were the postural-instability gait difficulty type. In 90.9% of the IPD cases with CMBs, the numbers of CMBs were three or less, whereas the numbers of CMBs exceeded three in 50% of the cases of VP and exceeded 10 in 31.3% of the cases (P < 0.001). The topography of the CMBs in IPD was also different from that in VP (P < 0.01). Cerebral microbleeds are not rare in IPD, and IPD with CMBs does not appear to be a form of VP. Further studies in larger populations are needed to elucidate the clinical implications of CMBs in terms of prognoses and cognitive changes in IPD. © 2014 EAN.

  16. Vascular Manifestations of von Recklinghausen's Disease

    PubMed Central

    Fye, Kenneth H.; Jacobs, Richard P.; Roe, Robert L.

    1975-01-01

    A casual relationship between von Recklinghausen's disease, or neurofibromatosis, and arteriolar abnormalities has been reported in the European literature. A patient was seen who had biopsy-proved neurofibromatosis and renovascular hypertension and retroperitoneal bleeding. An arteriographic study showed multiple small aneurysms throughout the coeliac axis, the superior mesenteric artery and in several small intrarenal vessels. Renal vein renin levels were elevated particularly in the right renal vein, supporting the diagnosis of renovascular hypertension. Both the aneurysms seen in angiographic studies and the retroperitoneal hemorrhage are probably vascular manifestations of von Recklinghausen's disease. Support for this conclusion is enhanced by the absence of clinical, laboratory or histologic data supporting the only tenable differential diagnosis, periarteritis nodosa. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:803743

  17. Vascular dysfunction in chronic obstructive pulmonary disease.

    PubMed

    Maclay, John D; McAllister, David A; Mills, Nicholas L; Paterson, Finny P; Ludlam, Christopher A; Drost, Ellen M; Newby, David E; Macnee, William

    2009-09-15

    Cardiovascular disease is a major cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), which may in part be attributable to abnormalities of systemic vascular function. It is unclear whether such associations relate to the presence of COPD or prior smoking habit. To undertake a comprehensive assessment of vascular function in patients with COPD and healthy control subjects matched for smoking history. Eighteen men with COPD were compared with 17 healthy male control subjects matched for age and lifetime cigarette smoke exposure. Participants were free from clinically evident cardiovascular disease. Pulse wave velocity and pulse wave analysis were measured via applanation tonometry at carotid, radial, and femoral arteries. Blood flow was measured in both forearms using venous occlusion plethysmography during intrabrachial infusion of endothelium-dependent vasodilators (bradykinin, 100-1,000 pmol/min; acetylcholine, 5-20 microg/min) and endothelium-independent vasodilators (sodium nitroprusside, 2-8 microg/min; verapamil, 10-100 microg/min). Tissue plasminogen activator (t-PA) was measured in venous plasma before and during bradykinin infusions. Patients with COPD have greater arterial stiffness (pulse wave velocity, 11 +/- 2 vs. 9 +/- 2 m/s; P = 0.003; augmentation index, 27 +/- 10 vs. 21 +/- 6%; P = 0.028), but there were no differences in endothelium-dependent and -independent vasomotor function or bradykinin-induced endothelial t-PA release (P > 0.05 for all). COPD is associated with increased arterial stiffness independent of cigarette smoke exposure. However, this abnormality is not explained by systemic endothelial dysfunction. Increased arterial stiffness may represent the mechanistic link between COPD and the increased risk for cardiovascular disease associated with this condition.

  18. Targeting pulmonary vascular disease to improve global health: pulmonary vascular disease: the global perspective.

    PubMed

    Rich, Stuart; Herskowitz, Ahvie

    2010-06-01

    Although there is widespread agreement on the need to address the glaring health-care disparities that exist in underserved countries in the world, there has not been an accepted approach to address these disparities that has proven to be successful. The international agenda has chosen to focus on maternal/fetal needs and infectious disease-based illnesses. However, cardiovascular diseases remain the leading cause of morbidity and mortality in the developing world. Since the adoption of the United Nations Millennium Development Goals in 2000, progress in raising the health-care standard in poorer countries has been slow. As an alternative approach, a global health-care strategy that targets cardiovascular disease may prove successful. The Pulmonary Vascular Research Institute has adopted a ground-up strategy by enlisting physicians from developing countries as partners in a virtual heart and lung institute. Realizing that pulmonary vascular disease is often a manifestation of advanced cardiovascular disease, we need to explore those illnesses that are prevalent in poorer countries where pulmonary hypertension is a resulting problem. Through education, capacity building, research, and clinical trials it should be possible to establish a successful paradigm that addresses the needs of patients and physicians while simultaneously expanding the knowledge and expertise about pulmonary vascular diseases worldwide. Eventually regional centers of excellence will be established worldwide that will serve the populace of both the developing and developed worlds combined.

  19. Antenatal betamethasone alters vascular reactivity in adult female ovine cerebral arteries.

    PubMed

    Eckman, Delrae M; Kerr, Brady A; Fuloria, Mamta; Simandle, Steve A; Watt, Suzanne E; Rose, James C; Figueroa, Jorge P

    2010-10-01

    Although the use of antenatal glucocorticoids has resulted in decreased neonatal morbidity/mortality, recent animal studies have raised concerns regarding adverse effects of these medications on postnatal cardiovascular function. We hypothesized that antenatal betamethasone (Beta) exposure alters cerebral vascular reactivity in adult female sheep. We observed that K-induced constriction was comparable in middle cerebral artery (MCA) from Beta-exposed animals and age-matched controls. Pressure-induced constriction was significantly attenuated in MCA from Beta-exposed compared with control sheep. Inhibition of NOS significantly augmented pressure-induced constriction in MCA from both Beta-exposed and control sheep, whereas cyclooxygenase (COX) inhibition augmented pressure-induced constriction only in MCA from Beta-exposed sheep. Furthermore, NOS and COX inhibition significantly attenuated bradykinin (BK)-induced dilation in MCA from both Beta-exposed and control sheep. However, there seemed to be a greater contribution of both NOS and COX to BK-induced dilation in Beta-exposed compared with control MCA. Our findings demonstrate that fetal exposure to a clinically relevant course of Beta alters cerebral vascular tone and reactivity in adult female sheep.

  20. Cerebral Cortex Structure in Prodromal Huntington Disease

    PubMed Central

    Nopoulos, Peggy C.; Aylward, Elizabeth H.; Ross, Christopher A.; Johnson, Hans J.; Magnotta, Vincent A.; Juhl, Andrew R.; Pierson, Ronald K.; Mills, James; Langbehn, Douglas R.; Paulsen, Jane S.

    2010-01-01

    Neuroimaging studies of subjects who are gene-expanded for Huntington Disease, but not yet diagnosed (termed prodromal HD), report that the cortex is “spared,” despite the decrement in striatal and cerebral white-matter volume. Measurement of whole-cortex volume can mask more subtle, but potentially clinically relevant regional changes in volume, thinning, or surface area. The current study addressed this limitation by evaluating cortical morphology of 523 prodromal HD subjects. Participants included 693 individuals enrolled in the PREDICT-HD protocol. Of these participants, 523 carried the HD gene mutation (prodromal HD group); the remaining 170 were non gene-expanded and served as the comparison group. Based on age and CAG repeat length, gene-expanded subjects were categorized as “Far from onset,” “Midway to onset,” “Near onset,” and “already diagnosed.” MRI scans were processed using FreeSurfer. Cortical volume, thickness, and surface area were not significantly different between the Far from onset group and controls. However, beginning in the Midway to onset group, the cortex showed significant volume decrement, affecting most the posterior and superior cerebral regions. This pattern progressed when evaluating the groups further into the disease process. Areas that remained mostly unaffected included ventral and medial regions of the frontal and temporal cortex. Morphologic changes were mostly in thinning as surface area did not substantially change in most regions. Early in the course of HD, the cortex shows changes that are manifest as cortical thinning and are most robust in the posterior and superior regions of the cerebrum. PMID:20688164

  1. Clinical Decision Support for Vascular Disease in Community Family Practice

    PubMed Central

    Keshavjee, K; Holbrook, AM; Lau, E; Esporlas-Jewer, I; Troyan, S

    2006-01-01

    The COMPETE III Vascular Disease Tracker (C3VT) is a personalized, Web-based, clinical decision support tool that provides patients and physicians access to a patient’s 16 individual vascular risk markers, specific advice for each marker and links to best practices in vascular disease management. It utilizes the chronic care model1 so that physicians can better manage patients with chronic diseases. Over 1100 patients have been enrolled into the COMPETE III study to date.

  2. Cerebral vascular amyloid seeds drive amyloid β-protein fibril assembly with a distinct anti-parallel structure

    PubMed Central

    Xu, Feng; Fu, Ziao; Dass, Sharmila; Kotarba, AnnMarie E.; Davis, Judianne; Smith, Steven O.; Van Nostrand, William E.

    2016-01-01

    Cerebrovascular accumulation of amyloid β-protein (Aβ), a condition known as cerebral amyloid angiopathy (CAA), is a common pathological feature of patients with Alzheimer's disease. Familial Aβ mutations, such as Dutch-E22Q and Iowa-D23N, can cause severe cerebrovascular accumulation of amyloid that serves as a potent driver of vascular cognitive impairment and dementia. The distinctive features of vascular amyloid that underlie its unique pathological properties remain unknown. Here, we use transgenic mouse models producing CAA mutants (Tg-SwDI) or overproducing human wild-type Aβ (Tg2576) to demonstrate that CAA-mutant vascular amyloid influences wild-type Aβ deposition in brain. We also show isolated microvascular amyloid seeds from Tg-SwDI mice drive assembly of human wild-type Aβ into distinct anti-parallel β-sheet fibrils. These findings indicate that cerebrovascular amyloid can serve as an effective scaffold to promote rapid assembly and strong deposition of Aβ into a unique structure that likely contributes to its distinctive pathology. PMID:27869115

  3. Microvasculature of the cerebral cortex: a vascular corrosion cast and immunocytochemical study.

    PubMed

    Scala, Gaetano

    2014-04-01

    In mammals, the cerebral cortex microvasculature (CCM) of the neopallium plays important roles in the physiological and pathological processes of the brain. The aim of the present work is to analyze the CCM by use of the SEM-vascular corrosion cast technique, and to examine the immunocytochemical characteristics of the CCM in adult domestic ruminants (cattle, buffalo, and sheep) by using the SEM-immunogold technique. The CCM originated from the very small, finger-like terminal branches of the macrovasculature of the brain. The superficial cortical arterioles were more numerous than the deep straight arterioles which proceeded toward the white matter. The surface casts of the arterioles and capillaries of the cerebral cortex showed ring-shaped formations in the arterioles and at the origin of the capillaries. All capillaries down-stream from these ring-shaped formations were flaccid. Casts of the capillaries showed wrinkles due to the presence of endothelial folds, which is characteristic of varying blood pressure. Formations having intense anti-GIFAP immunoreactivity were frequently evident along the course of the blood capillaries in the cerebral cortex. These formations were probably astrocytes that might regulate the cerebral microcirculation based on physiological and pathological stimuli, such as neuronal activation. Copyright © 2014 Wiley Periodicals, Inc.

  4. OBESITY INCREASES BLOOD PRESSURE, CEREBRAL VASCULAR REMODELING, AND SEVERITY OF STROKE IN THE ZUCKER RAT

    PubMed Central

    Osmond, Jessica M.; Mintz, James D.; Dalton, Brian; Stepp, David W.

    2009-01-01

    Obesity is a risk factor for stroke, but the mechanisms by which obesity increases stroke risk are unknown. Because microvascular architecture contributes to the outcome of stroke, we hypothesized that middle cerebral arteries (MCA) from obese Zucker rats (OZR) undergo inward remodeling and develop increased myogenic tone compared to lean Zucker rats (LZR). We further hypothesized that OZR have an increased infarct following cerebral ischemia and that changes in vascular structure and function correlate with the development of hypertension in OZR. Blood pressure was measured by telemetery in LZR and OZR from 6 to 17 weeks of age. Vessel structure and function were assessed in isolated MCAs. Stroke damage was assessed after ischemia was induced for 60 minutes followed by 24 hours of reperfusion. While mean arterial pressure (MAP) was similar between young rats (6–8 weeks old), MAP was higher in adult (14–17 weeks old) OZR than LZR. MCAs from OZR had a smaller lumen diameter and increased myogenic vasoconstriction compared to those from LZR. Following ischemia, infarction was 58% larger in OZR than LZR. Prior to the development of hypertension, MCA myogenic reactity and lumen diameter as well as infarct size were similar between young LZR and OZR. Our results indicate that the MCAs of OZR undergo structural remodeling and that these rats have greater cerebral injury following cerebral ischemia. These cerebrovascular changes correlate with the development of hypertension and suggest that the increased blood pressure may be the major determinant for stroke risk in obese individuals. PMID:19104000

  5. Ultrasound and dynamic functional imaging in vascular cognitive impairment and Alzheimer's disease.

    PubMed

    Malojcic, Branko; Giannakopoulos, Panteleimon; Sorond, Farzaneh A; Azevedo, Elsa; Diomedi, Marina; Oblak, Janja Pretnar; Carraro, Nicola; Boban, Marina; Olah, Laszlo; Schreiber, Stephan J; Pavlovic, Aleksandra; Garami, Zsolt; Bornstein, Nantan M; Rosengarten, Bernhard

    2017-02-09

    The vascular contributions to neurodegeneration and neuroinflammation may be assessed by magnetic resonance imaging (MRI) and ultrasonography (US). This review summarises the methodology for these widely available, safe and relatively low cost tools and analyses recent work highlighting their potential utility as biomarkers for differentiating subtypes of cognitive impairment and dementia, tracking disease progression and evaluating response to treatment in various neurocognitive disorders. At the 9th International Congress on Vascular Dementia (Ljubljana, Slovenia, October 2015) a writing group of experts was formed to review the evidence on the utility of US and arterial spin labelling (ASL) as neurophysiological markers of normal ageing, vascular cognitive impairment (VCI) and Alzheimer's disease (AD). Original articles, systematic literature reviews, guidelines and expert opinions published until September 2016 were critically analysed to summarise existing evidence, indicate gaps in current knowledge and, when appropriate, suggest standards of use for the most widely used US and ASL applications. Cerebral hypoperfusion has been linked to cognitive decline either as a risk or an aggravating factor. Hypoperfusion as a consequence of microangiopathy, macroangiopathy or cardiac dysfunction can promote or accelerate neurodegeneration, blood-brain barrier disruption and neuroinflammation. US can evaluate the cerebrovascular tree for pathological structure and functional changes contributing to cerebral hypoperfusion. Microvascular pathology and hypoperfusion at the level of capillaries and small arterioles can also be assessed by ASL, an MRI signal. Despite increasing evidence supporting the utility of these methods in detection of microvascular pathology, cerebral hypoperfusion, neurovascular unit dysfunction and, most importantly, disease progression, incomplete standardisation and missing validated cut-off values limit their use in daily routine. US and ASL are

  6. [Inflammatory cerebro-vascular disease: angiographic findings and distribution patterns (author's transl)].

    PubMed

    Stoeter, P; Ortega-Suhrkamp, E; Voigt, K

    1975-12-01

    Although cerebral angiography should be approached with caution in the diagnosis of inflammatory cerebro-vascular disease there are some characteristic angiographic findings which may be helpful for classification and differential diagnosis. The proximal cerebral arteries are favourably affected by basal meningitis and thrombangiitis obliterans with resulting stenoses and occlusions. Whereas those inflammations originating from neighbouring skull structures mostly involve the intracavernous parts of the carotid artery, the tuberculous and mycotic arteritis prefer the supraclinoid carotid siphon. Peripheral vascular changes are found in luetic endangiitis, necrotizing and toxic angiitis and in collagenoses. Simultaneous involvement of the temporal arteries is of great diagnostic importance demonstrating the systemic character of the inflammatory process; in Horton's arteritis it can be a pathognomonic finding. Infectious endocarditis, some mycoses and malaria may lead to embolic occlusion of cerebral vessels. Mycotic aneurysms mostly have a broad base or a fusiform shape and do not prefer the localizations of congenital aneurysms. Angiographically, abscesses, tuberculomas and viral encephalitis may result in circumscribed hypervascularized areas. The characteristic angiographic findings are exemplified and discussed on the basis of 8 cases of inflammatory cerebro-vascular disease (tuberculosis, pneumococcal and unspecific bacterial meningitis, syphilis, mycosis, Takayasu-syndrome, panarteritis nodosa, temporal arteritis).

  7. The rat cerebral vasculature exhibits time-of-day-dependent oscillations in circadian clock genes and vascular function that are attenuated following obstructive sleep apnea.

    PubMed

    Durgan, David J; Crossland, Randy F; Bryan, Robert M

    2017-08-01

    Circadian clock components oscillate in cells of the cardiovascular system. Disruption of these oscillations has been observed in cardiovascular diseases. We hypothesized that obstructive sleep apnea, which is associated with cerebrovascular diseases, disrupts the cerebrovascular circadian clock and rhythms in vascular function. Apneas were produced in rats during sleep. Following two weeks of sham or obstructive sleep apnea, cerebral arteries were isolated over 24 h for mRNA and functional analysis. mRNA expression of clock genes exhibited 24-h rhythms in cerebral arteries of sham rats (p < 0.05). Interestingly, peak expression of clock genes was significantly lower following obstructive sleep apnea (p < 0.05). Obstructive sleep apnea did not alter clock genes in the heart, or rhythms in locomotor activity. Isolated posterior cerebral arteries from sham rats exhibited a diurnal rhythm in sensitivity to luminally applied ATP, being most responsive at the beginning of the active phase (p < 0.05). This rhythm was absent in arteries from obstructive sleep apnea rats (p < 0.05). Rhythms in ATP sensitivity in sham vessels were absent, and not different from obstructive sleep apnea, following treatment with L-NAME and indomethacin. We conclude that cerebral arteries possess a functional circadian clock and exhibit a diurnal rhythm in vasoreactivity to ATP. Obstructive sleep apnea attenuates these rhythms in cerebral arteries, potentially contributing to obstructive sleep apnea-associated cerebrovascular disease.

  8. Unusual vascular events in the territory of the posterior cerebral artery.

    PubMed

    Fisher, C M

    1986-02-01

    There is an unusual type of vascular episode in the territory of the posterior cerebral artery which remains relatively unknown. Ten cases are presented in which a posterior cerebral artery deficit developed suddenly in dramatic fashion with headache, visual symptoms, sensory and motor deficits and signs of third nerve involvement. Nine of the patients were female and one was male. Seven were under the age of 33. In all instances there was a permanent neurologic sequela, usually a hemianopia. A similar case was described in 1901. The nature of the underlying process remains obscure, but the evidence favors accompanied migraine in which a particularly severe attack results in permanent damage. The term "catastrophic migraine" is suggested.

  9. Blood and CSF biomarkers in brain subcortical ischemic vascular disease: Involved pathways and clinical applicability

    PubMed Central

    Vilar-Bergua, A; Riba-Llena, I; Nafría, C; Bustamante, A; Llombart, V; Delgado, P

    2016-01-01

    Vascular dementia is the second most common type of dementia after Alzheimer’s disease (AD). Subcortical ischemic vascular disease refers to a form of vascular cognitive impairment characterized by the presence of diffuse white matter hyperintensities (WMHs) and multiple lacunar infarcts. These neuroimaging findings are mainly caused by cerebral small-vessel disease (cSVD) and relate to aging and cognitive impairment, but they can also be silent and highly prevalent in otherwise healthy individuals. We aimed to review studies on blood and cerebrospinal fluid (CSF) markers related to the presence of WMHs and lacunar infarcts that have been conducted in the past in large population-based studies and in high-risk selected patients (such as those with vascular risk factors, vascular cognitive impairment, or AD). Relevant associations with the presence and progression of cSVD have been described in the blood for markers related to inflammatory processes, endothelial damage and coagulation/fibrinolysis processes, etc. Also, different combinations of CSF markers might help to differentiate between etiologic types of dementia. In the future, to translate these findings into clinical practice and use biomarkers to early diagnosis and monitoring vascular cognitive impairment would require the replication of candidate markers in large-scale, multicenter, and prospectively designed studies. PMID:25899297

  10. CONTRIBUTION OF CEREBRAL VASCULAR ANOMALIES IN HEMORRHAGIC STROKE STRUCTURE IN DIFFERENT RACIAL GROUPS OF YAKUTIA.

    PubMed

    Chugunova, S A; Nikolaeva, T Y; Semenov, A

    2015-01-01

    Hemorrhagic stroke (HS) has higher incidence in Asian population compared to Caucasian. The reason for this phenomenon is not clearly understood. To investigate the contribution of cerebral vascular anomalies in hemorrhagic stroke structurein different racial groups of Yakutia. The study group included 1078 consecutively hospitalized patients with acute HS. A comparative analysis of demographic data and frequency of CVA, which were identified as a cause of HS, was carried out between the group of indigenous patients of Asian race and the group of Caucasian patients. The proportion of hemorrhage due to rupture of cerebralarterial aneurysms (CAA) in the hospital HS structure was higher in Asians, compared to Caucasians (p = 0.001; OR = 1.7; 95% CL: 1.2-2.4). No difference in the arteriovenous malformations' (AVM) frequency was found between groups (p = 0.345), as well as in age and gender distribution (p = 0.052 and p = 0.759, respectively). The CAA frequency was higher among female patients compared to male in both racial groups (p < 0.0001; OR = 1.71; CI 95% 1.3-2.3). In Yakutia, the proportion of hemorrhage due to rupture of cerebral arterial aneurysmsin hemorrhagic stroke structure is higher among indigenous ethnic group of Asian race, compared to Caucasians. No difference in the arteriovenous malformations' frequency was found between racial groups, as well as in age and gender distribution. The cerebral aneurisms' frequency was higher among female patients compared to male in both racial groups. Further studies of cerebral vascular anomalies and stroke risk factors using a population-based data in different racial groups are needed.

  11. A vascular disease educational program in the preclinical years of medical school increases student interest in vascular disease.

    PubMed

    Godshall, Christopher J; Moore, Phillip S; Fleming, Shawn H; Andrews, Jeanette S; Hansen, Kimberley J; Hoyle, John R; Edwards, Matthew S

    2010-09-01

    New training paradigms in vascular surgery necessitate medical student interest in vascular disease. We examined the effects of incorporation of a vascular disease educational program during the second year of the medical school curriculum on student acquisition of knowledge and interest in the treatment of vascular disease. We developed and administered a new educational program on vascular disease and delivered the program to all second-year medical students. The new program encompassed 9 didactic hours, including 7 traditional lecture hours and 2 hours of problem-based learning. After completing the program, students were surveyed regarding vascular disease-specific knowledge, interest in treating vascular disease, and career choices. Third-year students who were not exposed to the program were surveyed as a control group. We recorded the voluntary student enrollment in the vascular and endovascular surgery rotation during the following academic year. Voluntary enrollment of the students exposed to the vascular disease education program was compared with enrollment for the previous 8 years. Before the introduction of the new educational program, 946 total lecture hours were delivered to first- and second-year medical students, comprising 490 hours (52%) given by nonsurgeon physicians, 445 (47%) by nonphysicians, and 11 (1%) by surgeons. Survey response rate was 93% (112 of 121) for second-year students and 95% (39 of 41) for third-year students. After the vascular disease program, second-year students answered 7.1 +/- 1.4 of 9 vascular disease questions correctly, whereas unexposed third-year students answered 7.2 +/- 1.7 questions correctly (P = .96). Most second-year medical students described a "somewhat" or "much greater" interest in the medical (63%), procedural (59%), and overall (63%) management of vascular disease after exposure to the program. Most also had a "somewhat" or "much greater" interest in a vascular medicine (64%) or vascular and endovascular

  12. MMP-2 Is Mainly Expressed in Arterioles and Contributes to Cerebral Vascular Remodeling Associated with TGF-β1 Signaling.

    PubMed

    Hua, Ye; Zhang, Weifeng; Xie, Zhenying; Xu, Nanfei; Lu, Yunnan

    2016-07-01

    There is increasing evidence to suggest that matrix metalloproteinases (MMPs) play a crucial role in vascular remodeling. It has been reported that hypoxia stimulated MMP-9 expression in brain endothelial cells and MMP-9 plays an important role in cerebral vascular remodeling. However, little is known about MMP-2 in the cerebral vessels remodeling. Herein, the aim of this study is to examine the class of vessel and cell type expressing MMP-2 in cerebral vessels and to investigate its potential role in vascular remodeling. In the present study, dual-immunofluorescence assay showed that MMP-2 was mainly expressed in arterioles. In addition, we found that MMP-2 expression in cerebral vessels was derived from endothelial cells, not astrocyte cells. Notably, in the normoxic central nervous system (CNS), there was no effect on vascular development, integrity, or endothelial proliferation when MMP-2 was knocked out, but lack of MMP-2 led to defective arteriolar remodeling and associated with transforming growth factor β1 (TGF-β1) signaling in CNS. Moreover, blocking TGF-β with SB431542, a specific TGF-β inhibitor, significantly reduced the messenger RNA (mRNA) and protein expression levels of MMP-2 in human umbilical vein endothelial cells (HUVECs). Our findings reveal that the level of MMP-2 is high in arteriolar endothelial cells and demonstrate a novel connection between MMP-2 and TGF-β1 signaling in cerebral vascular remodeling.

  13. Decreased expression of transient receptor potential channels in cerebral vascular tissue from patients after hypertensive intracerebral hemorrhage.

    PubMed

    Thilo, Florian; Suess, Olaf; Liu, Ying; Tepel, Martin

    2011-01-01

    Recent data indicate that transient receptor potential (TRP) cation channels play an important role in hypertension. Now, we tested the hypothesis that TRP expression is altered in human cerebral vascular tissue in patients who had experienced hypertensive intracerebral hemorrhage. TRPC1, TRPC3, TRPC5, TRPC6, TRPM4, TRPM6, and TRPM7 channels were detected in cerebral vascular tissue by quantitative real-time RT-PCR. Control cerebral vascular tissue was obtained from normotensive patients who underwent neurosurgical operation because of brain tumor. To examine a possible relation between the expression of TRP expression and hypoxic conditions caused by the intracerebral bleeding, we examined the expression of hypoxia inducible factor 1a (HIF1a). Transcripts of TRPC3, TRPC5, TRPM6, and HIF1a were significantly reduced in cerebral vascular tissue from patients after hypertensive intracerebral hemorrhage compared to controls. TRPC3 mRNA correlated well with the expression of HIF1a mRNA (r(2) = 0.59; p = 0.01). TRPC3 expression is associated with hypertension and hypoxic conditions in human cerebral vascular tissue.

  14. Uric Acid, Hyperuricemia and Vascular Diseases

    PubMed Central

    Jin, Ming; Yang, Fan; Yang, Irene; Yin, Ying; Luo, Jin Jun; Wang, Hong; Yang, Xiao-Feng

    2011-01-01

    Uric acid is the product of purine metabolism. It is known that hyperuricemia, defined as high levels of blood uric acid, is the major etiological factor of gout. A number of epidemiological reports have increasingly linked hyperuricemia with cardiovascular and neurological diseases. Studies highlighting the pathogenic mechanisms of uric acid point to an inflammatory response as the primary mechanism for inducing gout and possibly contributing to uric acid's vascular effects. Monosodium urate (MSU) crystals induce an inflammatory reaction, which are recognized by Toll-like receptors (TLRs). These TLRs then activate NALP3 inflammasome. MSU also triggers neutrophil activation and further produces immune mediators, which lead to a proinflammatory response. In addition, soluble uric acid can also mediate the generation of free radicals and function as a pro-oxidant. This review summarizes the epidemiological studies of hyperuricemia and cardiovascular disease, takes a brief look at hyperuricemia and its role in neurological diseases, and highlights the studies of the advanced pathological mechanisms of uric acid and inflammation. PMID:22201767

  15. 2011 Vascular Research Initiatives Conference: basic foundations of translational research in vascular disease.

    PubMed

    Ziegler, Kenneth R; Dardik, Alan

    2011-07-01

    The Vascular Research Initiatives Conference (VRIC) is an annual conference organized by the Society for Vascular Surgery (SVS). The 2011 VRIC was held in Chicago (IL, USA) to precede and coincide with the first day of the meeting of the Council on Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) of the American Heart Association. The event is designed to present world class vascular research results, encourage collaboration between vascular surgeons and basic scientists in related disciplines, as well as to stimulate interest in research among aspiring academic vascular surgeons. The 2011 VRIC featured plenary sessions addressing peripheral arterial disease, vascular endothelium and thrombosis, aneurysms, and stem cells and tissue engineering. Recipients of the SVS partner grants with the National Institutes of Health K08 awardees presented their progress reports, and keynote addresses were given by Linda Graham and Frank LoGerfo.

  16. Vascular cognitive impairment: Modeling a critical neurologic disease in vitro and in vivo.

    PubMed

    Helman, Alex M; Murphy, M Paul

    2016-05-01

    Vascular contributions to cognitive impairment and dementia (VCID) is a complex form of dementia, combining aspects of vascular disease and other forms of dementia, such as Alzheimer's disease. VCID encompasses a wide spectrum of cerebrovascular-driven cognitive impairment, from mild cognitive impairment to fully developed dementia. This disease state is further complicated by metabolic disorders, such as type 2 diabetes and hypertension, and lifestyle factors, like obesity and high fat diets. This manuscript is meant to both define VCID and review the in vitro and in vivo models of the disease state. This includes in vitro models of the neurovascular unit, models of chronic cerebral hypoperfusion, animals with NOTCH3 mutations as a model of small vessel disease, large animals with cerebral amyloid angiopathy (CAA), and animal models of mixed dementia. Synthetic microvessels are a promising technique to study the neurovascular unit and canines, despite the cost, are an excellent model to study CAA. While there are several good models of individual aspects of VCID, the heterogeneity of the disease states prevents them from being a model of all aspects of the disease. Therefore, VCID needs to be further defined into disease states that exist within this umbrella term. This includes specific guidelines for stroke counts and stroke locations and further categorization of overlapping cerebrovascular and AD pathologies that contribute to dementia. This will allow for better models and a more thorough understanding of how vascular disease contributes to dementia. VCID is the second most common form of dementia and is expected to increase in coming years. The heterogeneity of VCID makes it difficult to study, but without better definitions and models, VCID presents a major public health problem for our aging population. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A

  17. Chronic resveratrol treatment restores vascular responsiveness of cerebral arterioles in type 1 diabetic rats

    PubMed Central

    Arrick, Denise M.; Sun, Hong; Patel, Kaushik P.

    2011-01-01

    Decreased dilation of cerebral arterioles via an increase in oxidative stress may be a contributing factor in the pathogenesis of diabetes-induced complications leading to cognitive dysfunction and/or stroke. Our goal was to determine whether resveratrol, a polyphenolic compound present in red wine, has a protective effect on cerebral arterioles during type 1 diabetes (T1D). We measured the responses of cerebral arterioles in untreated and resveratrol-treated (10 mg·kg−1·day−1) nondiabetic and diabetic rats to endothelial (eNOS) and neuronal (nNOS) nitric oxide synthase (NOS)-dependent agonists and to a NOS-independent agonist. In addition, we harvested brain tissue from nondiabetic and diabetic rats to measure levels of superoxide under basal conditions. Furthermore, we used Western blot analysis to determine the protein expression of eNOS, nNOS, SOD-1, and SOD-2 in cerebral arterioles and/or brain tissue from untreated and resveratrol-treated nondiabetic and diabetic rats. We found that T1D impaired eNOS- and nNOS-dependent reactivity of cerebral arterioles but did not alter NOS-independent vasodilation. While resveratrol did not alter responses in nondiabetic rats, resveratrol prevented T1D-induced impairment in eNOS- and nNOS-dependent vasodilation. In addition, superoxide levels were higher in brain tissue from diabetic rats and resveratrol reversed this increase. Furthermore, eNOS and nNOS protein were increased in diabetic rats and resveratrol produced a further increased eNOS and nNOS proteins. SOD-1 and SOD-2 proteins were not altered by T1D, but resveratrol treatment produced a decrease in SOD-2 protein. Our findings suggest that resveratrol restores vascular function and oxidative stress in T1D. We suggest that our findings may implicate an important therapeutic potential for resveratrol in treating T1D-induced cerebrovascular dysfunction. PMID:21666113

  18. Higher prevalence of spontaneous cerebral vasculopathy and cerebral infarcts in a mouse model of sickle cell disease.

    PubMed

    Hyacinth, Hyacinth I; Sugihara, Courtney L; Spencer, Thomas L; Archer, David R; Shih, Andy Y

    2017-01-01

    Stroke is a dramatic complication of sickle cell disease (SCD), which is associated with cerebral vasculopathies including moya moya, intravascular thrombi, cerebral hyperemia, and increased vessel tortuosity. The spontaneous occurrence of these pathologies in the sickle cell mouse model has not been described. Here, we studied Townes humanized sickle cell and age-matched control mice that were 13 months old. We used in vivo two-photon microscopy to assess blood flow dynamics, vascular topology, and evidence of cerebral vasculopathy. Results showed that compared to controls, sickle cell mice had significantly higher red blood cell (RBC) velocity (0.73 mm/s vs. 0.55 mm/s, p = 0.013), capillary vessel diameter (4.84 µM vs. 4.50 µM, p = 0.014), and RBC volume flux (0.015 nL/s vs. 0.010 nL/s, p = 0.021). Also, sickle cell mice had significantly more tortuous capillary vessels ( p < 0.0001) and significantly shorter capillary vessel branches ( p = 0.0065) compared to controls. Sickle cell mice also had significantly higher number of capillary occlusive events (3.4% vs. 1.9%, p < 0.0001) and RBC stalls (3.8% vs. 2.1%, p < 0.0001) in the cerebral capillary bed. In post-mortem immunohistochemical analyses, sickle cell mice had a 2.5-fold higher frequency of cortical microinfarcts compared to control mice. Our results suggest that aged Townes sickle cell mice spontaneously develop SCD-associated cerebral vasculopathy.

  19. Evidence of endothelial dysfunction in the development of Alzheimer's disease: Is Alzheimer's a vascular disorder?

    PubMed

    Kelleher, Rory J; Soiza, Roy L

    2013-11-01

    The etiology of Alzheimer's disease (AD) remains unclear. The emerging view is that cerebrovascular dysfunction is a feature not only of cerebrovascular diseases, such as stroke, but also of neurodegenerative conditions, such as AD. In AD, there is impaired structure and function of cerebral blood vessels and cells in the neurovascular unit. These effects are mediated by vascular oxidative stress. Injury to the neurovascular unit alters cerebral blood flow regulation, depletes vascular reserves, disrupts the blood-brain barrier and reduces the brain's repair capacity. Such injury can exacerbate the cognitive dysfunction exerted by incident ischemia and coexisting neurodegeneration. This article summarises data regarding cardiovascular risk factors, vascular abnormalities and brain endothelial damage in AD. In view of accumulating evidence of vascular pathology in AD, we also review the literature (MEDLINE, EMBASE) for clinical evidence of impaired endothelial function in AD. A total of 15 articles investigating endothelial dysfunction in AD were identified. 10 of these articles showed impaired endothelial function in AD patients. The current literature suggests endothelial dysfunction may be involved in the pathogenesis of AD. This aspect of AD pathology is particularly interesting in view of its potential for therapeutic intervention. Future research on endothelial function in AD should concentrate on population-based analysis and combine multiple methods to evaluate endothelial function.

  20. Stabiliztin of VEGFR2 Signaling by Cerebral Cavernous Malformation 3 is Critical for Vascular Development

    SciTech Connect

    Y He; H Zhang; L Yu; M Gunel; T Boggon; H Chen; W Min

    2011-12-31

    Cerebral cavernous malformations (CCMs) are human vascular malformations caused by mutations in three genes of unknown function: CCM1, CCM2, and CCM3. CCM3, also known as PDCD10 (programmed cell death 10), was initially identified as a messenger RNA whose abundance was induced by apoptotic stimuli in vitro. However, the in vivo function of CCM3 has not been determined. Here, we describe mice with a deletion of the CCM3 gene either ubiquitously or specifically in the vascular endothelium, smooth muscle cells, or neurons. Mice with global or endothelial cell-specific deletion of CCM3 exhibited defects in embryonic angiogenesis and died at an early embryonic stage. CCM3 deletion reduced vascular endothelial growth factor receptor 2 (VEGFR2) signaling in embryos and endothelial cells. In response to VEGF stimulation, CCM3 was recruited to and stabilized VEGFR2, and the carboxyl-terminal domain of CCM3 was required for the stabilization of VEGFR2. Indeed, the CCM3 mutants found in human patients lacking the carboxyl-terminal domain were labile and were unable to stabilize and activate VEGFR2. These results demonstrate that CCM3 promotes VEGFR2 signaling during vascular development.

  1. Stabilization of VEGFR2 signaling by cerebral cavernous malformation 3 is critical for vascular development.

    PubMed

    He, Yun; Zhang, Haifeng; Yu, Luyang; Gunel, Murat; Boggon, Titus J; Chen, Hong; Min, Wang

    2010-04-06

    Cerebral cavernous malformations (CCMs) are human vascular malformations caused by mutations in three genes of unknown function: CCM1, CCM2, and CCM3. CCM3, also known as PDCD10 (programmed cell death 10), was initially identified as a messenger RNA whose abundance was induced by apoptotic stimuli in vitro. However, the in vivo function of CCM3 has not been determined. Here, we describe mice with a deletion of the CCM3 gene either ubiquitously or specifically in the vascular endothelium, smooth muscle cells, or neurons. Mice with global or endothelial cell-specific deletion of CCM3 exhibited defects in embryonic angiogenesis and died at an early embryonic stage. CCM3 deletion reduced vascular endothelial growth factor receptor 2 (VEGFR2) signaling in embryos and endothelial cells. In response to VEGF stimulation, CCM3 was recruited to and stabilized VEGFR2, and the carboxyl-terminal domain of CCM3 was required for the stabilization of VEGFR2. Indeed, the CCM3 mutants found in human patients lacking the carboxyl-terminal domain were labile and were unable to stabilize and activate VEGFR2. These results demonstrate that CCM3 promotes VEGFR2 signaling during vascular development.

  2. Vascular Cures

    MedlinePlus

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  3. Mechanisms of vascular stability and the relationship to human disease

    PubMed Central

    Smith, Matthew C.P.; Li, Dean Y.; Whitehead, Kevin J.

    2010-01-01

    Purpose of review The genetic basis for a variety of vascular malformation syndromes have been described, with an increasing functional understanding of the associated genes. Recent findings Genes responsible for familial vascular malformation syndromes have increasingly been shown to be involved in the control of vascular stability. Summary Genes involved in vascular stability pathways are good candidates for causing vascular malformation syndromes. Although these findings confirm the biologic importance of the involved pathways, further explanations are required to describe the focal nature of disease. PMID:20308891

  4. Simvastatin combined with antioxidant attenuates the cerebral vascular endothelial inflammatory response in a rat traumatic brain injury.

    PubMed

    Wang, Kuo-Wei; Wang, Hao-Kuang; Chen, Han-Jung; Liliang, Po-Chou; Liang, Cheng-Loong; Tsai, Yu-Duan; Cho, Chung-Lung; Lu, Kang

    2014-01-01

    Traumatic brain injury (TBI) leads to important and deleterious neuroinflammation, as evidenced by indicators such as edema, cytokine production, induction of nitric oxide synthase, and leukocyte infiltration. After TBI, cerebral vascular endothelial cells play a crucial role in the pathogenesis of inflammation. In our previous study, we proved that simvastatin could attenuate cerebral vascular endothelial inflammatory response in a rat traumatic brain injury. This purpose of this study was to determine whether simvastatin combined with an antioxidant could produce the same effect or greater and to examine affected surrogate biomarkers for the neuroinflammation after traumatic brain injury in rat. In our study, cortical contusions were induced, and the effect of acute and continuous treatment of simvastatin and vitamin C on behavior and inflammation in adult rats following experimental TBI was evaluated. The results demonstrated that simvastatin combined with an antioxidant could provide neuroprotection and it may be attributed to a dampening of cerebral vascular endothelial inflammatory response.

  5. Vascular Inward Rectifier K+ Channels as External K+ Sensors in the Control of Cerebral Blood Flow

    PubMed Central

    LONGDEN, THOMAS A.; NELSON, MARK T.

    2015-01-01

    For decades it has been known that external potassium (K+) ions are rapid and potent vasodilators that increase cerebral blood flow (CBF). Recent studies have implicated the local release of K+ from astrocytic endfeet—which encase the entirety of the parenchymal vasculature—in the dynamic regulation of local CBF during neurovascular coupling (NVC). It has been proposed that the activation of strong inward rectifier K+ (KIR) channels in the vascular wall by external K+ is a central component of these hyperemic responses; however, a number of significant gaps in our knowledge remain. Here, we explore the concept that vascular KIR channels are the major extracellular K+ sensors in the control of CBF. We propose that K+ is an ideal mediator of NVC, and discuss KIR channels as effectors that produce rapid hyperpolarization and robust vasodilation of cerebral arterioles. We provide evidence that KIR channels, of the KIR2 subtype in particular, are present in both the endothelial and smooth muscle cells of parenchymal arterioles and propose that this dual positioning of KIR2 channels increases the robustness of the vasodilation to external K+, enables the endothelium to be actively engaged in neurovascular coupling, and permits electrical signaling through the endothelial syncytium to promote upstream vasodilation to modulate CBF. PMID:25641345

  6. Cerebral Arteriovenous Malformation Associated with Moyamoya Disease

    PubMed Central

    Noh, Jung-Hoon; Yeon, Je Young; Park, Jae-Han

    2014-01-01

    The coexistence of moyamoya disease (MMD) with an arteriovenous malformation (AVM) is exceedingly rare. We report two cases of AVM associated with MMD. The first case was an incidental AVM diagnosed simultaneously with MMD. This AVM was managed expectantly after encephalo-duro-arterio-synangiosis (EDAS) as the main feeders stemmed from the internal carotid artery, which we believed would be obliterated with the progression of MMD. However, the AVM persisted with replacement of the internal carotid artery feeders by new external carotid artery feeders from the EDAS site. The AVM was eventually treated with gamma knife radiosurgery considering an increasing steal effect. The second case was a de novo AVM case. The patient was initially diagnosed with MMD, and acquired an AVM eight years later that was slowly fed by the reconstituted anterior cerebral artery. Because the patient remained asymptomatic, the AVM is currently being closely followed for more than 2 years without further surgical intervention. Possible differences in the pathogenesis and the radiologic presentation of these AVMs are discussed with a literature review. No solid consensus exists on the optimal treatment of MMD-associated AVMs. Gamma knife radiosurgery appears to be an effective treatment option for an incidental AVM. However, a de novo AVM may be managed expectantly considering the possible risks of damaging established collaterals, low flow characteristics, and probably low risks of rupture. PMID:25371789

  7. Cerebral arteriovenous malformation associated with moyamoya disease.

    PubMed

    Noh, Jung-Hoon; Yeon, Je Young; Park, Jae-Han; Shin, Hyung Jin

    2014-10-01

    The coexistence of moyamoya disease (MMD) with an arteriovenous malformation (AVM) is exceedingly rare. We report two cases of AVM associated with MMD. The first case was an incidental AVM diagnosed simultaneously with MMD. This AVM was managed expectantly after encephalo-duro-arterio-synangiosis (EDAS) as the main feeders stemmed from the internal carotid artery, which we believed would be obliterated with the progression of MMD. However, the AVM persisted with replacement of the internal carotid artery feeders by new external carotid artery feeders from the EDAS site. The AVM was eventually treated with gamma knife radiosurgery considering an increasing steal effect. The second case was a de novo AVM case. The patient was initially diagnosed with MMD, and acquired an AVM eight years later that was slowly fed by the reconstituted anterior cerebral artery. Because the patient remained asymptomatic, the AVM is currently being closely followed for more than 2 years without further surgical intervention. Possible differences in the pathogenesis and the radiologic presentation of these AVMs are discussed with a literature review. No solid consensus exists on the optimal treatment of MMD-associated AVMs. Gamma knife radiosurgery appears to be an effective treatment option for an incidental AVM. However, a de novo AVM may be managed expectantly considering the possible risks of damaging established collaterals, low flow characteristics, and probably low risks of rupture.

  8. Placental growth factor deficiency is associated with impaired cerebral vascular development in mice.

    PubMed

    Luna, Rayana Leal; Kay, Vanessa R; Rätsep, Matthew T; Khalaj, Kasra; Bidarimath, Mallikarjun; Peterson, Nichole; Carmeliet, Peter; Jin, Albert; Croy, B Anne

    2016-02-01

    Placental growth factor (PGF) is expressed in the developing mouse brain and contributes to vascularization and vessel patterning. PGF is dynamically expressed in fetal mouse brain, particularly forebrain, and is essential for normal cerebrovascular development. PGF rises in maternal plasma over normal human and mouse pregnancy but is low in many women with the acute onset hypertensive syndrome, pre-eclampsia (PE). Little is known about the expression of PGF in the fetus during PE. Pgf  (-/-) mice appear normal but recently cerebral vascular defects were documented in adult Pgf  (-/-) mice. Here, temporal-spatial expression of PGF is mapped in normal fetal mouse brains and cerebral vasculature development is compared between normal and congenic Pgf  (-/-) fetuses to assess the actions of PGF during cerebrovascular development. Pgf/PGF, Vegfa/VEGF, Vegf receptor (Vegfr)1 and Vegfr2 expression were examined in the brains of embryonic day (E)12.5, 14.5, 16.5 and 18.5 C57BL/6 (B6) mice using quantitative PCR and immunohistochemistry. The cerebral vasculature was compared between Pgf  (-/-) and B6 embryonic and adult brains using whole mount techniques. Vulnerability to cerebral ischemia was investigated using a left common carotid ligation assay. Pgf/PGF and Vegfr1 are highly expressed in E12.5-14.5 forebrain relative to VEGF and Vegfr2. Vegfa/VEGF is relatively more abundant in hindbrain (HB). PGF and VEGF expression were similar in midbrain. Delayed HB vascularization was seen at E10.5 and 11.5 in Pgf  (-/-) brains. At E14.5, Pgf  (-/-) circle of Willis showed unilateral hypoplasia and fewer collateral vessels, defects that persisted post-natally. Functionally, adult Pgf  (-/-) mice experienced cerebral ischemia after left common carotid arterial occlusion while B6 mice did not. Since Pgf  (-/-) mice were used, consequences of complete absence of maternal and fetal PGF were defined. Therefore, the effects of maternal versus fetal PGF

  9. Cerebral microbleeds in patients with Parkinson's disease.

    PubMed

    Ham, Jee Hyun; Yi, Han; Sunwoo, Mun Kyung; Hong, Jin Yong; Sohn, Young H; Lee, Phil Hyu

    2014-08-01

    Cerebral microbleeds (CMBs) are known to be associated with cognitive impairments in the elderly and in patients with various diseases; however, the nature of this association has not yet been evaluated in Parkinson's disease (PD). In the present study, we analyzed the incidence of CMBs in PD according to cognitive status, and the impact of CMBs on cognitive performance was also evaluated. The CMBs in PD with dementia (n = 36), mild cognitive impairment (MCI, n = 46), or cognitively normal (n = 41) were analyzed using conventional T2*-weighted gradient-recalled echo images. Additionally, the relationship between the presence of CMBs and cognitive performance on individual tests of cognitive subdomains was analyzed using a detailed neuropsychological test. CMBs occurred more frequently in PD patients with dementia (36.1 %) compared to those with MCI (15.2 %), those who are cognitively normal (14.6 %), and normal controls (12.2 %, p = 0.025). However, the significant association of CMBs with PD dementia disappeared after adjusting white matter hyperintensities (WMHs) as a covariate. The frequencies of deep, lobar, and infratentorial CMBs did not differ among the four groups. After adjusting for age, sex, years of education, and WMHs, PD patients with CMBs had poorer performance in attention domain compared with those without CMBs (34.9 vs 42.6, p = 0.018). The present data demonstrate that even though CMBs were inseparably associated with the presence of WMHs, CMBs occur more commonly in PD patients with dementia than in those without dementia. Additionally, the burden of CMBs may contribute to further cognitive impairment in PD.

  10. [Frequency and causes of vascular complications requiring surgery in patients without primary vascular disease].

    PubMed

    Pongratz, J; Reeps, C; Eckstein, H-H

    2011-10-01

    Arterial and venous vascular injuries are known but rare complications of severe multiple traumatised patients but are meanwhile more frequently induced iatrogenically. However there are only few reports about incidence, causes, surgical techniques and prognosis of these vascular emergencies. We have therefore analysed the causes, type of therapy, localisation of injury, primary dis-ease, morbidity and mortality of all vascular emergencies in patients without preexisting vascular disease. 2.9 % of all vascular repairs in our unit had to be performed for cases of iatrogenic (87 %) and non-iatrogenic (13 %) vascular complications. The overall mortality and major complication rate of these intrahospital iatrogenically aquired lesions were 4.8 % and 5 %, respectively, which are clearly below those of extrahospital vascular injuries. Thereby the observed increase of iatrogenic vascular injuries seems to be due to the increase in complex and even catheter-based techniques in modern therapy. The iliacofemoral region was affected in 45 % of the cases, in 50 % complex reconstructions and specific surgical skills were needed for the repair. This article on the incidence of and reasons for vascular iatrogenic lesions shows the importance of a planned management for the prognosis of these injuries.

  11. Smoking and vascular risk: are all forms of smoking harmful to all types of vascular disease?

    PubMed

    Katsiki, N; Papadopoulou, S K; Fachantidou, A I; Mikhailidis, D P

    2013-05-01

    Smoking, both active and passive, is an established vascular risk factor. The present narrative review considers the effects of different forms of smoking (i.e. cannabis, cigar, pipe, smokeless tobacco and cigarette) on cardiovascular risk. Furthermore, the impact of smoking on several vascular risk factors [e.g. hypertension, diabetes mellitus (DM), dyslipidaemia and haemostasis] and on vascular diseases such as coronary heart disease (CHD), peripheral arterial disease (PAD), abdominal aortic aneurysms (AAA) and carotid arterial disease, is discussed. The adverse effects of all forms of smoking and the interactions between smoking and established vascular risk factors highlight the importance of smoking cessation in high-risk patients in terms of both primary and secondary vascular disease prevention. Healthcare providers should discourage people (especially the young) from becoming smokers, strongly encourage all vascular patients to stop smoking and support those who decide to quit by pharmaceutical and psychological interventions. In high-risk populations such as patients with CHD, DM and/or PAD, smoking cessation should always be a part of a multifactorial treatment to reduce vascular risk. Copyright © 2013 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  12. Vascular Endothelial Growth Factor in Eye Disease

    PubMed Central

    Penn, J.S.; Madan, A.; Caldwell, R.B.; Bartoli, M.; Caldwell, R.W.; Hartnett, M.E.

    2012-01-01

    Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis. PMID:18653375

  13. Plasmodium falciparum histidine-rich protein II causes vascular leakage and exacerbates experimental cerebral malaria in mice.

    PubMed

    Pal, Priya; Balaban, Amanda E; Diamond, Michael S; Sinnis, Photini; Klein, Robyn S; Goldberg, Daniel E

    2017-01-01

    A devastating complication of Plasmodium falciparum infection is cerebral malaria, in which vascular leakage and cerebral swelling lead to coma and often death. P. falciparum produces a protein called histidine-rich protein II (HRPII) that accumulates to high levels in the bloodstream of patients and serves as a diagnostic and prognostic marker for falciparum malaria. Using a human cerebral microvascular endothelial barrier model, we previously found that HRPII activates the endothelial cell inflammasome, resulting in decreased integrity of tight junctions and increased endothelial barrier permeability. Here, we report that intravenous administration of HRPII induced blood-brain barrier leakage in uninfected mice. Furthermore, HRPII infusion in P. berghei-infected mice increased early mortality from experimental cerebral malaria. These data support the hypothesis that HRPII is a virulence factor that contributes to cerebral malaria by compromising the integrity of the blood-brain barrier.

  14. Taxifolin inhibits amyloid-β oligomer formation and fully restores vascular integrity and memory in cerebral amyloid angiopathy.

    PubMed

    Saito, Satoshi; Yamamoto, Yumi; Maki, Takakuni; Hattori, Yorito; Ito, Hideki; Mizuno, Katsuhiko; Harada-Shiba, Mariko; Kalaria, Raj N; Fukushima, Masanori; Takahashi, Ryosuke; Ihara, Masafumi

    2017-04-04

    Cerebral amyloid angiopathy (CAA) induces various forms of cerebral infarcts and hemorrhages from vascular amyloid-β accumulation, resulting in acceleration of cognitive impairment, which is currently untreatable. Soluble amyloid-β protein likely impairs cerebrovascular integrity as well as cognitive function in early stage Alzheimer's disease. Taxifolin, a flavonol with strong anti-oxidative and anti-glycation activities, has been reported to disassemble amyloid-β in vitro but the in vivo relevance remains unknown. Here, we investigated whether taxifolin has therapeutic potential in attenuating CAA, hypothesizing that inhibiting amyloid-β assembly may facilitate its clearance through several elimination pathways. Vehicle- or taxifolin-treated Tg-SwDI mice (commonly used to model CAA) were used in this investigation. Cognitive and cerebrovascular function, as well as the solubility and oligomerization of brain amyloid-β proteins, were investigated. Spatial reference memory was assessed by water maze test. Cerebral blood flow was measured with laser speckle flowmetry and cerebrovascular reactivity evaluated by monitoring cerebral blood flow changes in response to hypercapnia. Significantly reduced cerebrovascular pan-amyloid-β and amyloid-β1-40 accumulation was found in taxifolin-treated Tg-SwDI mice compared to vehicle-treated counterparts (n = 5). Spatial reference memory was severely impaired in vehicle-treated Tg-SwDI mice but normalized after taxifolin treatment, with scoring similar to wild type mice (n = 10-17). Furthermore, taxifolin completely restored decreased cerebral blood flow and cerebrovascular reactivity in Tg-SwDI mice (n = 4-6). An in vitro thioflavin-T assay showed taxifolin treatment resulted in efficient inhibition of amyloid-β1-40 assembly. In addition, a filter trap assay and ELISA showed Tg-SwDI mouse brain homogenates exhibited significantly reduced levels of amyloid-β oligomers in vivo after taxifolin treatment (n

  15. Combined gene therapy with vascular endothelial growth factor plus apelin in a chronic cerebral hypoperfusion model in rats.

    PubMed

    Hiramatsu, Masafumi; Hishikawa, Tomohito; Tokunaga, Koji; Kidoya, Hiroyasu; Nishihiro, Shingo; Haruma, Jun; Shimizu, Tomohisa; Takasugi, Yuji; Shinji, Yukei; Sugiu, Kenji; Takakura, Nobuyuki; Date, Isao

    2017-09-01

    OBJECTIVE The aim of this study was to evaluate whether combined gene therapy with vascular endothelial growth factor (VEGF) plus apelin during indirect vasoreconstructive surgery enhances brain angiogenesis in a chronic cerebral hypoperfusion model in rats. METHODS A chronic cerebral hypoperfusion model induced by the permanent ligation of bilateral common carotid arteries (CCAs; a procedure herein referred to as "CCA occlusion" [CCAO]) in rats was employed in this study. Seven days after the CCAO procedure, the authors performed encephalo-myo-synangiosis (EMS) and injected plasmid(s) into each rat's temporal muscle. Rats were divided into 4 groups based on which plasmid was received (i.e., LacZ group, VEGF group, apelin group, and VEGF+apelin group). Protein levels in the cortex and attached muscle were assessed with enzyme-linked immunosorbent assay (ELISA) on Day 7 after EMS, while immunofluorescent analysis of cortical vessels was performed on Day 14 after EMS. RESULTS The total number of blood vessels in the cortex on Day 14 after EMS was significantly larger in the VEGF group and the VEGF+apelin group than in the LacZ group (p < 0.05, respectively). Larger vessels appeared in the VEGF+apelin group than in the other groups (p < 0.05, respectively). Apelin protein on Day 7 after EMS was not detected in the cortex for any of the groups. In the attached muscle, apelin protein was detected only in the apelin group and the VEGF+apelin group. Immunofluorescent analysis revealed that apelin and its receptor, APJ, were expressed on endothelial cells (ECs) 7 days after the CCAO. CONCLUSIONS Combined gene therapy (VEGF plus apelin) during EMS in a chronic cerebral hypoperfusion model can enhance angiogenesis in rats. This treatment has the potential to be a feasible option in a clinical setting for patients with moyamoya disease.

  16. Delivery of Polymeric Nanoparticles to Target Vascular Diseases

    PubMed Central

    Agyare, Edward; Kandimalla, Karunyna

    2015-01-01

    Current advances in nanotechnology have paved the way for the early detection, prevention and treatment of various diseases such as vascular disorders and cancer. These advances have provided novel approaches or modalities of incorporating or adsorbing therapeutic, biosensor and targeting agents into/on nanoparticles. With significant progress, nanomedicine for vascular therapy has shown significant advantages over traditional medicine because of its ability to selectively target the disease site and reduce adverse side effects. Targeted delivery of nanoparticles to vascular endothelial cells or the vascular wall provides an effective and more efficient way for early detection and/or treatment of vascular diseases such as atherosclerosis, thrombosis and Cerebrovascular Amyloid Angiopathy (CAA). Clinical applications of biocompatible and biodegradable polymers in areas such as vascular graft, implantable drug delivery, stent devices and tissue engineering scaffolds have advanced the candidature of polymers as potential nano-carriers for vascular-targeted delivery of diagnostic agents and drugs. This review focuses on the basic aspects of the vasculature and its associated diseases and relates them to polymeric nanoparticle-based strategies for targeting therapeutic agents to diseased vascular site. PMID:26069867

  17. l-arginine and l-NMMA for assessing cerebral endothelial dysfunction in ischaemic cerebrovascular disease: A systematic review.

    PubMed

    Karlsson, William K; Sørensen, Caspar G; Kruuse, Christina

    2017-01-01

    Endothelial dysfunction (ED), in particular cerebral ED, may be an essential biomarker for ischaemic cerebrovascular disease. However, there is no consensus on methods to best estimate cerebral ED. In this systematic review, we evaluate the use of l-arginine and N(G) -monomethyl-l-arginine (l-NMMA) for assessment of cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was done. We included studies investigating cerebrovascular response to l-arginine or l-NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular disease. Seven studies (315 subjects) were eligible according to inclusion and exclusion criteria. Studies investigated the effect of age (n=2), type 2 diabetes mellitus (DM) (n=1), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (n=1), leukoaraiosis (n=1), and prior ischaemic stroke or transient ischaemic attack (TIA) (n=2) on cerebral ED. Most studies applied transcranial Doppler to quantify cerebral ED. Endothelium-dependent vasodilatation (EDV) induced by l-arginine was impaired in elderly and subjects with leukoaraiosis, but enhanced in CADASIL patients. Studies including subjects with prior ischaemic stroke or TIA reported both enhanced and impaired EDV to l-arginine. Responses to l-NMMA deviated between subjects with type 2 DM and the elderly. We found only few studies investigating cerebral endothelial responses to l-arginine and l-NMMA in subjects with vascular risk factors or ischaemic cerebrovascular disease. Inconsistencies in results were most likely due to variations in methods and included subject populations. In order to use cerebral ED as a prognostic marker, further studies are required to evaluate the association to cerebrovascular disease.

  18. Vascular lesions in mixed dementia, vascular dementia, and Alzheimer disease with cerebrovascular disease: the Kurihara Project.

    PubMed

    Meguro, Kenichi; Tanaka, Naofumi; Nakatsuka, Masahiro; Nakamura, Kei; Satoh, Masayuki

    2012-11-15

    The concept and diagnosis for mixed dementia is not simple, since it is difficult to identify the type and regions of cerebrovascular disease (CVD) responsible for causing dementia. An investigation is needed to confirm the presence of mixed dementia, those who met the criteria for Alzheimer's disease (AD) and those for vascular dementia (VaD). According to the community-based stroke, dementia, and bed-confinement prevention in Kurihara, northern Japan (Kurihara Project), the prevalence of dementia and dementing diseases was surveyed in 2008-2010. Five hundred and ninety people finally agreed to participate (47.0%), and 73 (12.4%) people were diagnosed with dementia according to the DSM-IV. Using MRI, intensive evaluations on CVDs were performed for the 49 dementia patients associated with CVDs (mixed dementia, VaD, and AD with CVD). For the mixed dementia group, all had left subcortical strategic CVDs. These included the caudate head and thalamus. For the VaD group, all patients had at least cortical CVDs or subcortical strategic CVDs. The AD with CVD group had non-strategic CVDs in cortical, subcortical, or other areas in 5 or 6 patients each. Two extreme concepts regarding CVD and dementia are possible. One is that there is no concept for mixed dementia or VaD. An alternative is that the vascular factor should be considered as primary. Our data showed an importance of cortical and subcortical "strategic" areas, the latter included thalamus and caudate head.

  19. Effect of combined VEGF165/ SDF-1 gene therapy on vascular remodeling and blood perfusion in cerebral ischemia.

    PubMed

    Hu, Guo-Jie; Feng, Yu-Gong; Lu, Wen-Peng; Li, Huan-Ting; Xie, Hong-Wei; Li, Shi-Fang

    2016-12-16

    OBJECTIVE Therapeutic neovascularization is a promising strategy for treating patients after an ischemic stroke; however, single-factor therapy has limitations. Stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) proteins synergistically promote angiogenesis. In this study, the authors assessed the effect of combined gene therapy with VEGF165 and SDF-1 in a rat model of cerebral infarction. METHODS An adenoviral vector expressing VEGF165 and SDF-1 connected via an internal ribosome entry site was constructed (Ad- VEGF165-SDF-1). A rat model of middle cerebral artery occlusion (MCAO) was established; either Ad- VEGF165-SDF-1 or control adenovirus Ad- LacZ was stereotactically microinjected into the lateral ventricle of 80 rats 24 hours after MCAO. Coexpression and distribution of VEGF165 and SDF-1 were examined by reverse-transcription polymerase chain reaction, Western blotting, and immunofluorescence. The neurological severity score of each rat was measured on Days 3, 7, 14, 21, and 28 after MCAO. Angiogenesis and vascular remodeling were evaluated via bromodeoxyuridine and CD34 immunofluorescence labeling. Relative cerebral infarction volumes were determined by T2-weighted MRI and triphenyltetrazolium chloride staining. Cerebral blood flow, relative cerebral blood volume, and relative mean transmit time were assessed using perfusion-weighted MRI. RESULTS The Ad- VEGF165-SDF-1 vector mediated coexpression of VEGF165 and SDF-1 in multiple sites around the ischemic core, including the cortex, corpus striatum, and hippocampal granular layer. Coexpression of VEGF165 and SDF-1 improved neural function, reduced cerebral infarction volume, increased microvascular density and promoted angiogenesis in the ischemic penumbra, and improved cerebral blood flow and perfusion. CONCLUSIONS Combined VEGF165 and SDF-1 gene therapy represents a potential strategy for improving vascular remodeling and recovery of neural function after cerebral

  20. Large-vessel correlates of cerebral small-vessel disease

    PubMed Central

    Brisset, Marion; Boutouyrie, Pierre; Pico, Fernando; Zhu, Yicheng; Zureik, Mahmoud; Schilling, Sabrina; Dufouil, Carole; Mazoyer, Bernard; Laurent, Stéphane

    2013-01-01

    Objective: Our aim was to investigate the relationship of carotid structure and function with MRI markers of cerebral ischemic small-vessel disease. Methods: The study comprised 1,800 participants (aged 72.5 ± 4.1 years, 59.4% women) from the 3C-Dijon Study, a population-based, prospective cohort study, who had undergone quantitative brain MRI and carotid ultrasound. We used multivariable logistic and linear regression adjusted for age, sex, and vascular risk factors. Results: Presence of carotid plaque and increasing carotid lumen diameter (but not common carotid artery intima-media thickness) were associated with higher prevalence of lacunar infarcts: odds ratio (OR) = 1.60 (95% confidence interval [CI]: 1.09–2.35), p = 0.02 and OR = 1.24 (95% CI: 1.02–1.50), p = 0.03 (by SD increase). Carotid plaque was also associated with large white matter hyperintensity volume (WMHV) (age-specific top quartile of WMHV distribution): OR = 1.32 (95% CI: 1.04–1.67), p = 0.02, independently of vascular risk factors. Increasing Young elastic modulus and higher circumferential wall stress, reflecting augmented carotid stiffness, were associated with increasing WMHV (effect estimate [β] ± standard error: 0.0003 ± 0.0001, p = 0.024; β ± standard error: 0.005 ± 0.002, p = 0.008). Large WMHV was also associated with increasing Young elastic modulus (OR = 1.22 [95% CI: 1.04–1.42], p = 0.01) and with decreasing distensibility coefficient (OR = 0.83 [95% CI: 0.69–0.99], p = 0.04), independently of vascular risk factors. Associations of carotid lumen diameter with lacunar infarcts and of carotid stiffness markers with WMHV were independent of carotid plaque. Conclusions: In addition to and independently of carotid plaque, increasing carotid lumen diameter and markers of carotid stiffness were associated with increasing prevalence of lacunar infarcts and increasing WMHV, respectively. PMID:23345633

  1. Monoclonality and cytogenetic abnormalities in hyaline vascular Castleman disease.

    PubMed

    Chang, Kung-Chao; Wang, Yu-Chu; Hung, Liang-Yi; Huang, Wan-Ting; Tsou, Jen-Hui; M Jones, Dan; Song, Hsiang-Lin; Yeh, Yu-Min; Kao, Lin-Yuan; Medeiros, L Jeffrey

    2014-06-01

    Hyaline vascular Castleman disease is traditionally regarded as a reactive hyperplastic process. Occasional cases, however, have been reported with cytogenetic anomalies bringing this concept into question. In this study, we used conventional and methylation-specific polymerase chain reaction methods to assess the human androgen receptor α (HUMARA) gene in 29 female patients with hyaline vascular Castleman disease and compared the results with three cases of plasma cell Castleman disease and 20 cases of age-matched lymphoid hyperplasia. We also assessed for immunoglobulin gene and T-cell receptor gene rearrangements, and conventional cytogenetic analysis was performed in three cases of hyaline vascular Castleman disease. In cases with informative results, conventional and methylation-specific human androgen receptor α gene analyses yielded a monoclonal pattern in 10 of 19 (53%) and 17 of 23 (74%) cases of hyaline vascular Castleman disease, respectively. A monoclonal pattern was also detected in three cases of plasma cell Castleman disease but not in cases of lymphoid hyperplasia. The frequency of monoclonality was higher for lesions >5 cm in size (100%) and for the stromal-rich variant (91%). Cytogenetic abnormalities in stromal cells were revealed in two cases of hyaline vascular Castleman disease and no cases showed monoclonal immunoglobulin or T-cell receptor gene rearrangements. Follow-up data showed persistent disease in 4 of 23 (17%) patients. We conclude that hyaline vascular Castleman disease is often a monoclonal proliferation, most likely of lymph node stromal cells.

  2. Clearance of cerebral Aβ in Alzheimer's disease: reassessing the role of microglia and monocytes.

    PubMed

    Zuroff, Leah; Daley, David; Black, Keith L; Koronyo-Hamaoui, Maya

    2017-06-01

    Deficiency in cerebral amyloid β-protein (Aβ) clearance is implicated in the pathogenesis of the common late-onset forms of Alzheimer's disease (AD). Accumulation of misfolded Aβ in the brain is believed to be a net result of imbalance between its production and removal. This in turn may trigger neuroinflammation, progressive synaptic loss, and ultimately cognitive decline. Clearance of cerebral Aβ is a complex process mediated by various systems and cell types, including vascular transport across the blood-brain barrier, glymphatic drainage, and engulfment and degradation by resident microglia and infiltrating innate immune cells. Recent studies have highlighted a new, unexpected role for peripheral monocytes and macrophages in restricting cerebral Aβ fibrils, and possibly soluble oligomers. In AD transgenic (ADtg) mice, monocyte ablation or inhibition of their migration into the brain exacerbated Aβ pathology, while blood enrichment with monocytes and their increased recruitment to plaque lesion sites greatly diminished Aβ burden. Profound neuroprotective effects in ADtg mice were further achieved through increased cerebral recruitment of myelomonocytes overexpressing Aβ-degrading enzymes. This review summarizes the literature on cellular and molecular mechanisms of cerebral Aβ clearance with an emphasis on the role of peripheral monocytes and macrophages in Aβ removal.

  3. Inapparent pulmonary vascular disease in an ex-heroin user

    SciTech Connect

    Antonelli Incalzi, R.; Ludovico Maini, C.; Giuliano Bonetti, M.; Campioni, P.; Pistelli, R.; Fuso, L.

    1986-04-01

    A severe pulmonary vascular derangement, usually reported in drug addicts, was diagnosed in a 28-year-old asymptomatic ex-heroin user by means of fortuitously performed pulmonary perfusion imaging. Neither physical findings nor pulmonary function tests, aroused suspicion of the diagnosis. A search for asymptomatic pulmonary vascular disease probably should be undertaken in drug addicts.

  4. Systemic atheromatosis influence on retinal vascular disease.

    PubMed

    Ştefănescu, A; Sas, T; Bătăiosu, C

    2014-01-01

    Clinical study on a group of 48 patients over 3 months: 27 patients were recruited from ophtalmology and 21 recruited from cardiology, 25 % of these patients coming for routine check. Patients were investigated by ophthalmic, cardiologic examination, imaging and laboratory tests. The study demonstrated the need for interdisciplinary consultation for patients with vascular complaints in carotid territory and a close correlation between the vascular pathology and ophthalmology at this level.

  5. Andrographolide, a Novel NF-κB Inhibitor, Inhibits Vascular Smooth Muscle Cell Proliferation and Cerebral Endothelial Cell Inflammation

    PubMed Central

    Chang, Chao-Chien; Duann, Yeh-Fang; Yen, Ting-Lin; Chen, Yu-Ying; Jayakumar, Thanasekaran; Ong, Eng-Thiam; Sheu, Joen-Rong

    2014-01-01

    Background Aberrant vascular smooth muscle cell (VSMC) proliferation and cerebral endothelial cell (CEC) dysfunction contribute significantly in the pathogenesis of cardiovascular diseases. Therefore, inhibition of these cellular events would be by candidate agents for treating these diseases. In the present study, the mechanism of anti-proliferative and anti-inflammatory effects of andrographolides, a novel nuclear factor-κB inhibitor, was investigated in VSMC and CEC cells. Methods VSMCs and CECs were isolated from rat artery and mouse brain, respectively, and cultured before experimentation. The effect of andro on platelet-derived growth factor-BB (PDGF-BB) induced VSMC cell proliferation was evaluated by cell number, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of extracellular signal regulated kinase 1/2 (ERK1/2), proliferating cell nuclear antigen (PCNA), and the effects on lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) and, cyclooxygenase-2 (COX2) were detected by Western blotting. Results Andro significantly inhibited PDGF-BB (10 ng/ml) induced cell proliferation in a concentration (20-100 μM) dependent manner, which may be due to reducing the expression of ERK1/2, and by inhibiting the expression of PCNA. Andro also remarkably diminished LPS-induced iNOS and COX2 expression. Conclusions The results of this study suggested that the effects of andro against VSMCs proliferation and CECs dysfunction may represent a promising approach for treatment of vascular diseases. PMID:27122804

  6. Nursing diagnoses in patients with cerebral vascular accident: an integrative review.

    PubMed

    Lima, Ana Carolina Maria Araújo Chagas Costa; Silva, Aurilene Lima da; Guerra, Débora Rodrigues; Barbosa, Islene Victor; Bezerra, Karine de Castro; Oriá, Mônica Oliveira Batista

    2016-01-01

    to verify the nursing diagnoses in patients affected by CVAs. this is an integrative review of the literature. The search was conducted on LILACS, Scielo, Medline, CINAHL, and Scopus databases between February and March 2015, using the following keywords: "Enfermagem", "Acidente Vascular Cerebral", "Diagnóstico de Enfermagem"; and "Nursing", "Stroke", and "Nursing Diagnosis". we found 9 articles published between 2009 and 2015; most of them were Brazilian, cross-sectional, and exploratory, with a level of evidence of 6. The evidence from the publications was classified as: "Evaluation and validation of specific nursing diagnoses for subjects affected by CVAs" and "Application of the nursing process on subjects affected by CVAs". we noticed the publications focused on nursing diagnoses related to motor disorders, such as risk of falls and impaired physical mobility. Domains regarding safety/protection (domain 11) and sleep/resting (domain 4) were present in most evaluated publications.

  7. Matrix metalloproteinase-9 mediates post-hypoxic vascular pruning of cerebral blood vessels by degrading laminin and claudin-5.

    PubMed

    Boroujerdi, Amin; Welser-Alves, Jennifer V; Milner, Richard

    2015-07-01

    Vascular remodeling involves a highly coordinated break-down and build-up of the vascular basal lamina and inter-endothelial tight junction proteins. In light of the important role of matrix metalloproteinases (MMPs) in tissue remodeling, the goal of this study was to examine the role of MMP-9 in remodeling of cerebral blood vessels, both in hypoxia-induced angiogenesis and in the vascular pruning that accompanies the switch from hypoxia back to normoxia. In a chronic mild hypoxia model of cerebrovascular remodeling, gel zymography revealed that MMP-9 levels were increased, both during hypoxic-induced angiogenesis and in the post-hypoxic pruning response. Interestingly, compared to wild-type mice, MMP-9 KO mice showed no alteration in hypoxic-induced angiogenesis, but did show marked delay in post-hypoxic vascular pruning. In wild-type mice, vascular pruning was associated with fragmentation of vascular laminin and the tight junction protein claudin-5, while this process was markedly attenuated in MMP-9 KO mice. In vitro experiments showed that hypoxia stimulated MMP-9 expression in brain endothelial cells but not pericytes. These results show that while MMP-9 is not essential for hypoxic-induced cerebral angiogenesis, it plays an important role in post-hypoxic vascular pruning by degrading laminin and claudin-5.

  8. Vascular targeting of nanoparticles for molecular imaging of diseased endothelium.

    PubMed

    Atukorale, Prabhani U; Covarrubias, Gil; Bauer, Lisa; Karathanasis, Efstathios

    2016-09-15

    This review seeks to highlight the enormous potential of targeted nanoparticles for molecular imaging applications. Being the closest point-of-contact, circulating nanoparticles can gain direct access to targetable molecular markers of disease that appear on the endothelium. Further, nanoparticles are ideally suitable to vascular targeting due to geometrically enhanced multivalent attachment on the vascular target. This natural synergy between nanoparticles, vascular targeting and molecular imaging can provide new avenues for diagnosis and prognosis of disease with quantitative precision. In addition to the obvious applications of targeting molecular signatures of vascular diseases (e.g., atherosclerosis), deep-tissue diseases often manifest themselves by continuously altering and remodeling their neighboring blood vessels (e.g., cancer). Thus, the remodeled endothelium provides a wide range of targets for nanoparticles and molecular imaging. To demonstrate the potential of molecular imaging, we present a variety of nanoparticles designed for molecular imaging of cancer or atherosclerosis using different imaging modalities.

  9. Assessment of risk of peripheral vascular disease and vascular care capacity in Ghana

    PubMed Central

    Gyedu, Adam; Stewart, Barclay T; Nakua, Emmanuel; Quansah, Robert; Donkor, Peter; Mock, Charles; Hardy, Mark A; Yangni-Angate, Koffi Herve

    2015-01-01

    Introduction This study aimed to describe national peripheral vascular disease (PVD) risk and health burden and vascular care capacity in Ghana. The gap between PVD burden and vascular care capacity in a low- and middle-income country (LMIC) is defined and capacity improvement priorities identified. Methods Data to estimate PVD risk factor burden were obtained from: i) World Health Organization’s Study on Global Ageing and Health (SAGE), Ghana; and ii) Institute of Health Metrics and Evaluation Global Burden of Disease database (IHME GBD). In addition, a novel nationwide assessment of vascular care capacity was performed, with 20 vascular care items assessed at 40 hospitals in Ghana. Factors contributing to specific item deficiency were also described. Results From the SAGE database, there were 4,305 respondents aged at least 50 years with data to estimate PVD risk. Out of these 57% were at moderate to high PVD risk with ≥3 risk factors, thus giving 1,654,557 persons when extrapolated nationally. Using IHME GBD data, the estimated disability-adjusted life years incurred from PVD increased 5-fold from 1990 to 2010 (1.3 to 3.2 per 100,000 persons, respectively). Vascular care capacity assessment demonstrated marked deficiencies in items for diagnosis, perioperative and vascular surgical care. Deficiencies were most often due to absence of equipment, lack of training and technology breakage. Conclusion Risk factor reduction and management as well as optimization of current resources are paramount to avoid the large burden of peripheral vascular disease falling on healthcare systems in low- and middle-income countries that are not well equipped to handle vascular surgical care, and for which rapid development of such capacity would be difficult and expensive. PMID:26560502

  10. Multichannel optical brain imaging to separate cerebral vascular, tissue metabolic, and neuronal effects of cocaine

    NASA Astrophysics Data System (ADS)

    Ren, Hugang; Luo, Zhongchi; Yuan, Zhijia; Pan, Yingtian; Du, Congwu

    2012-02-01

    Characterization of cerebral hemodynamic and oxygenation metabolic changes, as well neuronal function is of great importance to study of brain functions and the relevant brain disorders such as drug addiction. Compared with other neuroimaging modalities, optical imaging techniques have the potential for high spatiotemporal resolution and dissection of the changes in cerebral blood flow (CBF), blood volume (CBV), and hemoglobing oxygenation and intracellular Ca ([Ca2+]i), which serves as markers of vascular function, tissue metabolism and neuronal activity, respectively. Recently, we developed a multiwavelength imaging system and integrated it into a surgical microscope. Three LEDs of λ1=530nm, λ2=570nm and λ3=630nm were used for exciting [Ca2+]i fluorescence labeled by Rhod2 (AM) and sensitizing total hemoglobin (i.e., CBV), and deoxygenated-hemoglobin, whereas one LD of λ1=830nm was used for laser speckle imaging to form a CBF mapping of the brain. These light sources were time-sharing for illumination on the brain and synchronized with the exposure of CCD camera for multichannel images of the brain. Our animal studies indicated that this optical approach enabled simultaneous mapping of cocaine-induced changes in CBF, CBV and oxygenated- and deoxygenated hemoglobin as well as [Ca2+]i in the cortical brain. Its high spatiotemporal resolution (30μm, 10Hz) and large field of view (4x5 mm2) are advanced as a neuroimaging tool for brain functional study.

  11. [Prevention of vascular events after transient ischemic attack or cerebral infarct].

    PubMed

    Leys, Didier; Cordonnier, Charlotte

    2006-09-15

    After a first cerebral ischemic event, secondary prevention should be started as soon as possible, especially in transient ischemic attacks where the risk of recurrence is the highest, especially during the first week, needing a diagnostic workup in a short period of time, secondary prevention measures depending on the presumed cause of the event. Secondary prevention of vascular events after transient ischemic attack or cerebral infarct consists of 3 types of strategies: 1. treatment of risk factors for stroke, especially high blood pressure, high cholesterol and smoking cessation; 2. aspirin (50 to 325 mg), or clopidogrel, or association aspirine-dipyridamole in high-risk subjects, or warfarin in patients with high-risk cardiopathies; and 3. carotid surgery in patients selected by clinical and imaging criteria. Other strategies are currently partly under evaluation: statins in normocholesterolemic ischemic stroke patients without coronary event, angioplasty with stenting. Audits of practice are necessary to determine whether patients are actually treated according to scientific evidence. This is a crucial issue if we want the results of trials to be translated in the true life, and really improve health at the community level.

  12. Biomedicine and diseases: the Klippel-Trenaunay syndrome, vascular anomalies and vascular morphogenesis

    PubMed Central

    Timur, A. A.; Driscoll, D. J.

    2006-01-01

    Vascular morphogenesis is a vital process for embryonic development, normal physiologic conditions (e.g. wound healing) and pathological processes (e.g. atherosclerosis, cancer). Genetic studies of vascular anomalies have led to identification of critical genes involved in vascular morphogenesis. A susceptibility gene, VG5Q (formally named AGGF1), was cloned for Klippel-Trenaunay syndrome (KTS). AGGF1 encodes a potent angiogenic factor, and KTS-associated mutations enhance angiogenic activity of AGGF1, defining ‘increased angiogenesis’ as one molecular mechanism for the pathogenesis of KTS. Similar studies have identified other genes involved in vascular anomalies as important genes for vascular morphogenesis, including TIE2, VEGFR-3, RASA1, KRIT1, MGC4607, PDCD10, glomulin, FOXC2, NEMO, SOX18, ENG, ACVRLK1, MADH4, NDP, TIMP3, Notch3, COL3A1 and PTEN. Future studies of vascular anomaly genes will provide insights into the molecular mechanisms for vascular morphogenesis, and may lead to the development of therapeutic strategies for treating these and other angiogenesis-related diseases, including coronary artery disease and cancer. PMID:15905966

  13. Pathophysiology of white matter perfusion in Alzheimer's disease and vascular dementia.

    PubMed

    Barker, Rachel; Ashby, Emma L; Wellington, Dannielle; Barrow, Vivienne M; Palmer, Jennifer C; Kehoe, Patrick G; Esiri, Margaret M; Love, Seth

    2014-05-01

    of reduced ratio of myelin-associated glycoprotein to proteolipid protein 1 are likely to be protective physiological responses to reduced white matter perfusion. Further analysis of the Bristol cohort showed that endothelin 1 was reduced in the white matter in Alzheimer's disease (P < 0.05) compared with control subjects, but not in vascular dementia, in which endothelin 1 tended to be elevated, perhaps reflecting abnormal regulation of white matter perfusion in vascular dementia. Our findings demonstrate the potential of post-mortem measurement of myelin proteins and mediators of vascular function, to assess physiological and pathological processes involved in the regulation of cerebral perfusion in Alzheimer's disease and vascular dementia.

  14. Pathophysiology of white matter perfusion in Alzheimer’s disease and vascular dementia

    PubMed Central

    Barker, Rachel; Ashby, Emma L.; Wellington, Dannielle; Barrow, Vivienne M.; Palmer, Jennifer C.; Kehoe, Patrick G.; Esiri, Margaret M.

    2014-01-01

    context of reduced ratio of myelin-associated glycoprotein to proteolipid protein 1 are likely to be protective physiological responses to reduced white matter perfusion. Further analysis of the Bristol cohort showed that endothelin 1 was reduced in the white matter in Alzheimer’s disease (P < 0.05) compared with control subjects, but not in vascular dementia, in which endothelin 1 tended to be elevated, perhaps reflecting abnormal regulation of white matter perfusion in vascular dementia. Our findings demonstrate the potential of post-mortem measurement of myelin proteins and mediators of vascular function, to assess physiological and pathological processes involved in the regulation of cerebral perfusion in Alzheimer’s disease and vascular dementia. PMID:24618270

  15. The adverse effects of reduced cerebral perfusion on cognition and brain structure in older adults with cardiovascular disease

    PubMed Central

    Alosco, Michael L; Gunstad, John; Jerskey, Beth A; Xu, Xiaomeng; Clark, Uraina S; Hassenstab, Jason; Cote, Denise M; Walsh, Edward G; Labbe, Donald R; Hoge, Richard; Cohen, Ronald A; Sweet, Lawrence H

    2013-01-01

    Background It is well established that aging and vascular processes interact to disrupt cerebral hemodynamics in older adults. However, the independent effects of cerebral perfusion on neurocognitive function among older adults remain poorly understood. We examined the associations among cerebral perfusion, cognitive function, and brain structure in older adults with varying degrees of vascular disease using perfusion magnetic resonance imaging (MRI) arterial spin labeling (ASL). Materials and methods 52 older adults underwent neuroimaging and were administered the Mini Mental State Examination (MMSE), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and measures of attention/executive function. ASL and T1-weighted MRI were used to quantify total brain perfusion, total brain volume (TBV), and cortical thickness. Results Regression analyses showed reduced total brain perfusion was associated with poorer performance on the MMSE, RBANS total index, immediate and delayed memory composites, and Trail Making Test B. Reduced frontal lobe perfusion was associated with worse executive and memory function. A similar pattern emerged between temporal lobe perfusion and immediate memory. Regression analyses revealed that decreased total brain perfusion was associated with smaller TBV and mean cortical thickness. Regional effects of reduced total cerebral perfusion were found on temporal and parietal lobe volumes and frontal and temporal cortical thickness. Discussion Reduced cerebral perfusion is independently associated with poorer cognition, smaller TBV, and reduced cortical thickness in older adults. Conclusion Prospective studies are needed to clarify patterns of cognitive decline and brain atrophy associated with cerebral hypoperfusion. PMID:24363966

  16. Atrial fibrillation and vascular disease--a bad combination.

    PubMed

    Olesen, Jonas Bjerring; Gislason, Gunnar Hilmar; Torp-Pedersen, Christian; Lip, Gregory Y H

    2012-01-01

    This article provides an overview of (i) the risk of stroke associated with vascular disease (acute coronary syndromes and peripheral artery disease) in patients with atrial fibrillation, (ii) the frequent coexistence of vascular disease in patients with atrial fibrillation and, (iii) the cardiovascular risk associated with the coexisting of the two diseases. The literature on this topic is relatively sparse, and we discuss results from both clinical trials and observational studies. There is a clear indication of an increased stroke risk associated with vascular disease in patients with atrial fibrillation. Indeed, patients with atrial fibrillation often had coexisting vascular disease (around 18%), and the combination of the two diseases substantially increases the risk of future cardiovascular events. The increased risk associated with peripheral artery disease in atrial fibrillation is even more pronounced. Patients with atrial fibrillation and stable vascular disease should be treated with oral anticoagulation only, although when these patients present with acute coronary syndrome and/or undergo coronary stenting, concomitant treatment with antiplatelet drugs is indicated. To guide antithrombotic management in patients with atrial fibrillation, several stroke and bleeding risk prediction schemes have been developed. © 2012 Wiley Periodicals, Inc.

  17. Kienböck's disease in cerebral palsy.

    PubMed

    Rooker, G D; Goodfellow, J W

    1977-08-01

    Five cases of Kienböck's disease occurring in a group of fifty-three adults with cerebral palsy are described. The increased incidence of the disease is attributed to the flexed posture habitual in the affected wrist and to an effect on the pattern of blood supply to the lunate.

  18. Oscillation of Angiogenesis and Vascular Dropout in Progressive Human Vascular Disease. [Vascular Pattern as Useful Read-Out of Complex Molecular Signaling

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, Patricia

    2010-01-01

    When analyzed by VESsel GENeration Analysis (VESGEN) software, vascular patterns provide useful integrative read-outs of complex, interacting molecular signaling pathways. Using VESGEN, we recently discovered and published our innovative, surprising findings that angiogenesis oscillated with vascular dropout throughout progression of diabetic retinopathy, a blinding vascular disease. Our findings provide a potential paradigm shift in the current prevailing view on progression and treatment of this disease, and a new early-stage window of regenerative therapeutic opportunities. The findings also suggest that angiogenesis may oscillate with vascular disease in a homeostatic-like manner during early stages of other inflammatory progressive diseases such as cancer and coronary vascular disease.

  19. Vascular calcification in patients with chronic kidney disease.

    PubMed

    Nitta, Kosaku

    2011-12-01

    Vascular calcification is very prevalent in patients with chronic kidney disease (CKD). In addition to having more traditional cardiovascular (CV) risk factors, CKD patients also have a number of non-traditional CV risk factors that may play a prominent role in the pathogenesis of vascular calcification. The transformation of vascular smooth muscle cells into osteoblast-like cells seems to be a key element in the pathogenesis of vascular calcification in the presence of calcium (Ca) and phosphorus (P) deposition due to abnormal bone metabolism and impaired renal excretion. Vascular calcification causes increased arterial stiffness, left ventricular hypertrophy, decreased coronary artery perfusion, myocardial ischemia, and increased cardiovascular morbidity and mortality. Although current treatment strategies focus on correcting abnormal Ca, P, parathyroid hormone, or vitamin D levels in CKD, a better understanding of the mechanisms of abnormal tissue calcification may lead to the development of new therapeutic agents that are capable of reducing vascular calcification and improving the CV outcome of CKD patients. This review article summarizes the following: (i) the pathophysiological mechanism responsible for vascular calcification; (ii) the methods of detecting vascular calcification in CKD patients; and (iii) the treatment of vascular calcification in CKD patients. © 2011 The Author. Therapeutic Apheresis and Dialysis © 2011 International Society for Apheresis.

  20. On the measurement of absolute cerebral blood volume (CBV) using vascular-space-occupancy (VASO) MRI.

    PubMed

    Uh, Jinsoo; Lewis-Amezcua, Kelly; Varghese, Rani; Lu, Hanzhang

    2009-03-01

    Recently, a vascular-space-occupancy (VASO) MRI technique was developed for quantitative assessment of cerebral blood volume (CBV). This method uses the T(1)-shortening effect of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) with imaging parameters chosen that null the precontrast blood magnetization but allow the postcontrast blood magnetization to recover to equilibrium. A key advantage of VASO CBV estimation is that it provides a straightforward procedure for converting MR signals to absolute physiologic values. However, as with other T(1)-based steady-state approaches, several important factors need to be considered that influence the accuracy of CBV values obtained with VASO MRI. Here, the transverse relaxation (T(2)/T(2) (*)) effect in VASO MRI was investigated using multiecho spin-echo and gradient-echo experiments, resulting in underestimation of CBV by 14.9% +/- 1.1% and 16.0% +/- 2.5% for spin echo (TE = 10 ms) and gradient echo (TE = 6 ms), respectively. In addition, the influence of contrast agent clearance was studied by acquiring multiple postcontrast VASO images at 2.2-min intervals, which showed that the concentration of Gd-DTPA in the first 14 min (single dose) was sufficient for the blood magnetization to fully recover to equilibrium. Finally, the effect of vascular Gd-DTPA leakage was assessed for scalp tissue, and signal extrapolation as a function of postinjection time was demonstrated to be useful in minimizing the associated errors. Specific recommendations for VASO MRI acquisition and processing strategies are provided.

  1. Selective arterial distribution of cerebral hyperperfusion in Fabry disease.

    PubMed

    Moore, D F; Herscovitch, P; Schiffmann, R

    2001-07-01

    Fabry disease is an X-linked recessive deficiency of lysosomal alpha-galactosidase A associated with an increased risk of early onset cerebrovascular disease. The disorder is reported to affect the posterior circulation predominantly. This hypothesis was investigated directly by the measurement of regional cerebral blood flow with positron emission tomography (PET). Resting regional cerebral blood flow (rCBF) in 26 hemizygous patients with Fabry disease and 10 control participants was examined using H(2)15O and PET. Statistical parametric mapping (SPM(t), SPM99) and PET images of patients and controls were produced. Significantly increased SPM(t) clusters were then color coded and blended with a coregistered T1 magnetic resonance imaging (MRI) template. Cerebral arterial territory maps were digitized and rescaled. Custom OpenGL and ImageVision Library C++ code was written to allow a first-order affine transformation of the blended SPM(t) and MRI template onto the arterial territory map. The affine transformation was constrained by choosing corresponding cerebral landmark "tie points" between the SPM(t) [symbol: see text] MRI template images and the cerebral arterial territory maps. The data demonstrated that the posterior circulation is the predominant arterial territory with a significantly increased rCBF in Fabry disease. No arterial distribution had a decreased rCBF.

  2. Excessive vascular sprouting underlies cerebral hemorrhage in mice lacking αVβ8-TGFβ signaling in the brain.

    PubMed

    Arnold, Thomas D; Niaudet, Colin; Pang, Mei-Fong; Siegenthaler, Julie; Gaengel, Konstantin; Jung, Bongnam; Ferrero, Gina M; Mukouyama, Yoh-suke; Fuxe, Jonas; Akhurst, Rosemary; Betsholtz, Christer; Sheppard, Dean; Reichardt, Louis F

    2014-12-01

    Vascular development of the central nervous system and blood-brain barrier (BBB) induction are closely linked processes. The role of factors that promote endothelial sprouting and vascular leak, such as vascular endothelial growth factor A, are well described, but the factors that suppress angiogenic sprouting and their impact on the BBB are poorly understood. Here, we show that integrin αVβ8 activates angiosuppressive TGFβ gradients in the brain, which inhibit endothelial cell sprouting. Loss of αVβ8 in the brain or downstream TGFβ1-TGFBR2-ALK5-Smad3 signaling in endothelial cells increases vascular sprouting, branching and proliferation, leading to vascular dysplasia and hemorrhage. Importantly, BBB function in Itgb8 mutants is intact during early stages of vascular dysgenesis before hemorrhage. By contrast, Pdgfb(ret/ret) mice, which exhibit severe BBB disruption and vascular leak due to pericyte deficiency, have comparatively normal vascular morphogenesis and do not exhibit brain hemorrhage. Our data therefore suggest that abnormal vascular sprouting and patterning, not BBB dysfunction, underlie developmental cerebral hemorrhage.

  3. Clinical imaging of vascular disease in chronic kidney disease.

    PubMed

    Sag, Alan A; Covic, Adrian; London, Gerard; Vervloet, Marc; Goldsmith, David; Gorriz, Jose Luis; Kanbay, Mehmet

    2016-06-01

    Arterial wall calcification, once considered an incidental finding, is now known to be a consistent and strong predictor of cardiovascular events in patients with chronic renal insufficiency. It is also commonly encountered in radiologic examinations as an incidental finding. Forthcoming bench, translational, and clinical data seek to establish this and pre-calcification changes as surrogate imaging biomarkers for noninvasive prognostication and treatment follow-up. Emerging paradigms seek to establish vascular calcification as a surrogate marker of disease. Imaging of pre-calcification and decalcification events may prove more important than imaging of the calcification itself. Data-driven approaches to screening will be necessary to limit radiation exposure and prevent over-utilization of expensive imaging techniques.

  4. Current management of peripheral vascular disease: where is the evidence?

    PubMed

    Saha, Sibu P; Whayne, Thomas F; Mukherjee, Debabrata P

    2011-04-01

    The presence of peripheral vascular disease along with coronary heart disease are the two components of generalized atherosclerosis. The risk of having one when the other is present is extremely high. There are four parts to consider in peripheral vascular disease management and these are prevention, plaque stabilization, percutaneous intervention and surgery. Each part has its place but no one would argue that prevention is best when risk is recognized and treated. Classic risk factors and the available diagnostic methods are discussed. Treatment of risk factors is presented with reduction of the low density lipoproteins as the established gold standard during the current era. Procedures of percutaneous vascular intervention with their procedural indications are presented and their advantages and disadvantages discussed. Surgical indications are presented with special indication due to major claudication, rest pain, or tissue loss. Prognosis is also considered and this prognosis is worse in more proximal peripheral vascular disease. Association with other diseases is an important part of prognosis, with the latter especially made worse by the presence of diabetes mellitus. Surprisingly, the long-term prognosis of peripheral vascular disease is worse than that of coronary heart disease. These patients have a significant increase of cardiovascular risk factors and of comorbidities. It has been shown that these patients are undertreated in spite of their high cardiovascular risk. It is mandatory that they receive the same intensive treatment of risk factors as that given to coronary heart disease patients.

  5. Emerging diagnostic and therapeutic molecular imaging applications in vascular disease

    PubMed Central

    Eraso, Luis H; Reilly, Muredach P; Sehgal, Chandra; Mohler, Emile R

    2013-01-01

    Assessment of vascular disease has evolved from mere indirect and direct measurements of luminal stenosis to sophisticated imaging methods to depict millimeter structural changes of the vasculature. In the near future, the emergence of multimodal molecular imaging strategies may enable robust therapeutic and diagnostic (‘theragnostic’) approaches to vascular diseases that comprehensively consider structural, functional, biological and genomic characteristics of the disease in individualized risk assessment, early diagnosis and delivery of targeted interventions. This review presents a summary of recent preclinical and clinical developments in molecular imaging and theragnostic applications covering diverse atherosclerosis events such as endothelial activation, macrophage infammatory activity, plaque neovascularization and arterial thrombosis. The main focus is on molecular targets designed for imaging platforms commonly used in clinical medicine including magnetic resonance, computed tomography and positron emission tomography. A special emphasis is given to vascular ultrasound applications, considering the important role this imaging platform plays in the clinical and research practice of the vascular medicine specialty. PMID:21310769

  6. Endothelial fluid shear stress sensing in vascular health and disease

    PubMed Central

    Baeyens, Nicolas; Bandyopadhyay, Chirosree; Coon, Brian G.; Yun, Sanguk; Schwartz, Martin A.

    2016-01-01

    Endothelial cells transduce the frictional force from blood flow (fluid shear stress) into biochemical signals that regulate gene expression and cell behavior via specialized mechanisms and pathways. These pathways shape the vascular system during development and during postnatal and adult life to optimize flow to tissues. The same pathways also contribute to atherosclerosis and vascular malformations. This Review covers recent advances in basic mechanisms of flow signaling and the involvement of these mechanisms in vascular physiology, remodeling, and these diseases. We propose that flow sensing pathways that govern normal morphogenesis can contribute to disease under pathological conditions or can be altered to induce disease. Viewing atherosclerosis and vascular malformations as instances of pathological morphogenesis provides a unifying perspective that may aid in developing new therapies. PMID:26928035

  7. Aβ immunotherapy for Alzheimer's disease: effects on apoE and cerebral vasculopathy.

    PubMed

    Sakai, Kenji; Boche, Delphine; Carare, Roxana; Johnston, David; Holmes, Clive; Love, Seth; Nicoll, James A R

    2014-12-01

    Aβ immunotherapy for Alzheimer's disease (AD) results in the removal of Aβ plaques and increased cerebral amyloid angiopathy (CAA). In current clinical trials, amyloid-related imaging abnormalities (ARIAs), putatively due to exacerbation of CAA, are concerning side effects. We aimed to assess the role of the Aβ transporter apolipoprotein E (apoE) in the exacerbation of CAA and development of CAA-associated vasculopathy after Aβ immunotherapy. 12 Aβ42-immunized AD (iAD; AN1792, Elan Pharmaceuticals) cases were compared with 28 unimmunized AD (cAD) cases. Immunohistochemistry was quantified for Aβ42, apoE, apoE E4 and smooth muscle actin, and CAA-associated vasculopathy was analyzed. Aβ immunotherapy was associated with redistribution of apoE from cortical plaques to cerebral vessel walls, mirroring the altered distribution of Aβ42. Concentric vessel wall splitting was increased threefold in leptomeningeal vessels after immunotherapy (cAD 6.3 vs iAD 20.6 %, P < 0.001), but smooth muscle cell abnormalities did not differ. The findings suggest that apoE is involved in the removal of plaques and transport of Aβ to the cerebral vasculature induced by Aβ immunotherapy. Immunotherapy was not associated with CAA-related vascular smooth muscle damage, but was accompanied by increased splitting of the vessel wall, perhaps reflecting enhanced deposition and subsequent removal of Aβ. ARIA occurring in some current trials of Aβ immunotherapy may reflect an extreme form of these vascular changes.

  8. Vascular dysfunction associated with type 2 diabetes and Alzheimer's disease: a potential etiological linkage.

    PubMed

    Wang, Fuzhou; Guo, Xirong; Shen, Xiaofeng; Kream, Richard M; Mantione, Kirk J; Stefano, George B

    2014-08-01

    The endothelium performs a crucial role in maintaining vascular integrity leading to whole organ metabolic homeostasis. Endothelial dysfunction represents a key etiological factor leading to moderate to severe vasculopathies observed in both Type 2 diabetic and Alzheimer's Disease (AD) patients. Accordingly, evidence-based epidemiological factors support a compelling hypothesis stating that metabolic rundown encountered in Type 2 diabetes engenders severe cerebral vascular insufficiencies that are causally linked to long term neural degenerative processes in AD. Of mechanistic importance, Type 2 diabetes engenders an immunologically mediated chronic pro-inflammatory state involving interactive deleterious effects of leukocyte-derived cytokines and endothelial-derived chemotactic agents leading to vascular and whole organ dysfunction. The long term negative consequences of vascular pro-inflammatory processes on the integrity of CNS basal forebrain neuronal populations mediating complex cognitive functions establish a striking temporal comorbidity of AD with Type 2 diabetes. Extensive biomedical evidence supports the pivotal multi-functional role of constitutive nitric oxide (NO) production and release as a critical vasodilatory, anti-inflammatory, and anti-oxidant, mechanism within the vascular endothelium. Within this context, we currently review the functional contributions of dysregulated endothelial NO expression to the etiology and persistence of Type 2 diabetes-related and co morbid AD-related vasculopathies. Additionally, we provide up-to-date perspectives on critical areas of AD research with special reference to common NO-related etiological factors linking Type 2 diabetes to the pathogenesis of AD.

  9. Arterial disease and vascular access in diabetic patients.

    PubMed

    Baktiroglu, Selcuk; Yanar, Fatih; Ozata, Ibrahim H; Oner, Gizem; Ercan, Damla

    2016-03-01

    There are conflicting reports on the effects of diabetes on the outcomes of hemodialysis access procedures. While some found no negative effects, others reported deleterious effects of diabetes on vascular access outcomes. Why is there concern about diabetes and related vascular problems on vascular access procedures? What are the differences of diabetic patients and their vasculature from that of nondiabetics? Do they have an effect on hemodialysis vascular access outcomes? We will try to find answers to these questions in light of the available evidence. Recent literature on arterial disease in diabetes and end-stage renal disease (ESRD), and the effects on vascular access outcomes were searched in order to find answers to above questions. There are conflicting and controversial reports on the effects of preexisting vascular problems due to diabetes and chronic kidney disease (CKD) on the outcomes of hemodialysis access procedures. Diabetic vasculature, especially in patients with ESRD, has some specific problems, the most important of which seem to be the calcification and stiffening of the arteries. Although some authors report inferior outcomes of vascular access procedures in diabetic patients, there is evidence that most of the problems encountered can be dealt with by careful patient selection, surgical skill, and experience.

  10. Cerebral blood flow and metabolism associated with cerebral microbleeds in small vessel disease.

    PubMed

    Hashimoto, Tetsuya; Yokota, Chiaki; Koshino, Kazuhiro; Shimomura, Ryo; Hino, Tenyu; Moriguchi, Tetsuaki; Hori, Yuki; Uehara, Toshiyuki; Minematsu, Kazuo; Iida, Hidehiro; Toyoda, Kazunori

    2016-08-01

    Cerebral microbleeds (CMBs), probably reflecting microangiopathy, have not yet sufficiently been examined in association with cerebral blood flow (CBF) and metabolism. We investigated the relationships between CMBs, and CBF and metabolism in symptomatic small vessel disease. We enrolled 22 patients with symptomatic small vessel disease without severe stenosis (>50 %) in major cerebral arteries. Volumes of white matter lesions (WMLs) and number of CMBs were assessed on images of fluid-attenuated inversion recovery and gradient-echo T2*-weighted magnetic resonance imaging, respectively. Patients were divided into two groups according to the median number of CMBs (group I <5, n = 10; group II ≥5, n = 12). Parametric images of CBF, cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction and cerebral blood volume were estimated using positron emission tomography and (15)O-labeled gases. The functional values in the cortex-subcortex, basal ganglia, and centrum semiovale were compared between the two groups. Volumes of WMLs of group II were larger than those of group I (median: 38.4; range: 25.1-91.5 mL vs. median: 11.3; range: 4.2-73.4 mL, p = 0.01). In the centrum semiovale, the mean CBF of group II was significantly lower than that of group I (12.6 ± 2.6 vs. 15.6 ± 3.3 mL/100 g/min, p = 0.04). In the other regions, there were no significant differences in either CBF or CMRO2 between the two groups. Our study indicated that increases in the number of CMBs with larger volumes of WMLs were associated with cerebral ischemia in the deep white matter in patients with symptomatic small vessel disease.

  11. Infarctions in the vascular territory of the posterior cerebral artery: clinical features in 232 patients

    PubMed Central

    2011-01-01

    Background Ischemic stroke caused by infarction in the territory of the posterior cerebral artery (PCA) has not been studied as extensively as infarctions in other vascular territories. This single centre, retrospective clinical study was conducted a) to describe salient characteristics of stroke patients with PCA infarction, b) to compare data of these patients with those with ischaemic stroke due to middle cerebral artery (MCA) and anterior cerebral artery (ACA) infarctions, and c) to identify predictors of PCA stroke. Findings A total of 232 patients with PCA stroke were included in the "Sagrat Cor Hospital of Barcelona Stroke Registry" during a period of 19 years (1986-2004). Data from stroke patients are entered in the stroke registry following a standardized protocol with 161 items regarding demographics, risk factors, clinical features, laboratory and neuroimaging data, complications and outcome. The characteristics of these 232 patients with PCA stroke were compared with those of the 1355 patients with MCA infarctions and 51 patients with ACA infarctions included in the registry. Infarctions of the PCA accounted for 6.8% of all cases of stroke (n = 3808) and 9.6% of cerebral infarctions (n = 2704). Lacunar infarction was the most frequent stroke subtype (34.5%) followed by atherothrombotic infarction (29.3%) and cardioembolic infarction (21.6%). In-hospital mortality was 3.9% (n = 9). Forty-five patients (19.4%) were symptom-free at hospital discharge. Hemianopia (odds ratio [OR] = 6.43), lacunar stroke subtype (OR = 2.18), symptom-free at discharge (OR = 1.92), limb weakness (OR = 0.10), speech disorders (OR = 0.33) and cardioembolism (OR = 0.65) were independent variables of PCA stroke in comparison with MCA infarction, whereas sensory deficit (OR = 2.36), limb weakness (OR = 0.11) and cardioembolism as stroke mechanism (OR = 0.43) were independent variables associated with PCA stroke in comparison with ACA infarction. Conclusions Lacunar stroke is the

  12. Disruption of rich club organisation in cerebral small vessel disease.

    PubMed

    Tuladhar, Anil M; Lawrence, Andrew; Norris, David G; Barrick, Thomas R; Markus, Hugh S; de Leeuw, Frank-Erik

    2017-04-01

    Cerebral small vessel disease (SVD) is an important cause of vascular cognitive impairment. Recent studies have demonstrated that structural connectivity of brain networks in SVD is disrupted. However, little is known about the extent and location of the reduced connectivity in SVD. Here they investigate the rich club organisation-a set of highly connected and interconnected regions-and investigate whether there is preferential rich club disruption in SVD. Diffusion tensor imaging (DTI) and cognitive assessment were performed in a discovery sample of SVD patients (n = 115) and healthy control subjects (n = 50). Results were replicated in an independent dataset (49 SVD with confluent WMH cases and 108 SVD controls) with SVD patients having a similar SVD phenotype to that of the discovery cases. Rich club organisation was examined in structural networks derived from DTI followed by deterministic tractography. Structural networks in SVD patients were less dense with lower network strength and efficiency. Reduced connectivity was found in SVD, which was preferentially located in the connectivity between the rich club nodes rather than in the feeder and peripheral connections, a finding confirmed in both datasets. In discovery dataset, lower rich club connectivity was associated with lower scores on psychomotor speed (β = 0.29, P < 0.001) and executive functions (β = 0.20, P = 0.009). These results suggest that SVD is characterized by abnormal connectivity between rich club hubs in SVD and provide evidence that abnormal rich club organisation might contribute to the development of cognitive impairment in SVD. Hum Brain Mapp 38:1751-1766, 2017. © 2017 Wiley Periodicals, Inc.

  13. The use of erythtropoietin in cerebral diseases.

    PubMed

    Cotena, S; Piazza, O; Tufano, R

    2008-06-01

    Global and focal cerebral ischemia is followed by a secondary damage characterized by oxidative stress, excitotoxicity, inflammation and apoptosis. Erythropoietin (EPO) exerts antiapoptotic, anti-inflammatory, antioxidative, angiogenetic and neurotrophic properties. Its potential therapeutic role has been demonstrated in several animal models of cerebral ischemia and also in a clinical trial of ischemic stroke, so it could be considered an ideal compound for neuroprotection in ischemic stroke and in cardiac arrest. Intracerebral hemorrhage (ICH) is the least treatable form of stroke; the mechanisms involved in the secondary brain injury include hematoma mass effect, neuronal apoptosis and necrosis, inflammation. It has been demonstrated in an experimental ICH that EPO intervenes in the inflammatory process, reduces brain water content, hemorrhage volume and hemispheric atrophy, promotes cell survival, preserves cerebral blood flow, has antiapoptotic protective function against oxidative stress and excitotoxic damage. EPO can attenuate acute vasoconstriction and prevent brain ischemic damage in subarachnoid hemorrhage. The neuroprotective function of EPO has been studied also in traumatic brain injury: it reduces the inflammation and improves cognitive and motor deficits. The authors review some of the physiological actions of EPO in the physiopathology of ischemic and hemorrhagic stroke, subarachnoid hemorrhage and brain trauma, and its potential usefulness in the brain injured patient management.

  14. Interplay between coagulation and vascular inflammation in sickle cell disease

    PubMed Central

    Sparkenbaugh, Erica; Pawlinski, Rafal

    2013-01-01

    Sickle cell disease is the most common inherited hematologic disorder that leads to the irreversible damage of multiple organs. Although sickling of red blood cells and vaso-occlusion are central to the pathophysiology of sickle cell disease the importance of hemolytic anemia and vasculopathy has been recently recognized. Hypercoagulation state is another prominent feature of sickle cell disease and is mediated by activation of both intrinsic and extrinsic coagulation pathways. Growing evidence demonstrates that coagulation may not only contribute to the thrombotic complications, but also to vascular inflammation associated with this disease. This article summarizes the role of vascular inflammation and coagulation activation, discusses potential mechanisms responsible for activation of coagulation and reviews recent data demonstrating the crosstalk between coagulation and vascular inflammation in sickle cell disease. PMID:23593937

  15. Optical measures of changes in cerebral vascular tone during voluntary breath holding and a Sternberg memory task.

    PubMed

    Tan, Chin Hong; Low, Kathy A; Schneider-Garces, Nils; Zimmerman, Benjamin; Fletcher, Mark A; Maclin, Edward L; Chiarelli, Antonio M; Gratton, Gabriele; Fabiani, Monica

    2016-07-01

    The human cerebral vasculature responds to changes in blood pressure and demands for oxygenation via cerebral autoregulation. Changes in cerebrovascular tone (vasoconstriction and vasodilation) also mediate the changes in blood flow measured by the BOLD fMRI signal. This cerebrovascular reactivity is known to vary with age. In two experiments, we demonstrate that cerebral pulse parameters measured using optical imaging can quantify changes in cerebral vascular tone, both globally and locally. In experiment 1, 51 older adults (age range=55-87) performed a voluntary breath-holding task while cerebral pulse amplitude measures were taken. We found significant pulse amplitude variations across breath-holding periods, indicating vasodilation during, and vasoconstriction after breath holding. The breath-holding index (BHI), a measure of cerebrovascular reactivity (CVR) was derived and found to correlate with age. BHI was also correlated with performance in the Modified Mini-Mental Status Examination, even after controlling for age and education. In experiment 2, the same participants performed a Sternberg task, and changes in regional pulse amplitude between high (set-size 6) and low (set-size 2) task loads were compared. Only task-related areas in the fronto-parietal network (FPN) showed significant reduction in pulse amplitude, indicating vasodilation. Non-task-related areas such as the somatosensory and auditory cortices did not show such reductions. Taken together, these experiments suggest that optical pulse parameters can index changes in brain vascular tone both globally and locally, using both physiological and cognitive load manipulations.

  16. Matrix Metalloproteinases and their Inhibitors in Vascular Remodeling and Vascular Disease

    PubMed Central

    Raffetto, Joseph D.; Khalil, Raouf A.

    2008-01-01

    Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade various components of the extracellular matrix (ECM). Members of the MMP family include collagenases, gelatinases, stromelysins, matrilysins and membrane-type MMPs. ProMMPs are cleaved into active forms that promote degradation of ECM proteins. Also, recent evidence suggests direct or indirect effects of MMPs on ion channels in the endothelium and vascular smooth muscle, and on other mechanisms of vascular relaxation/contraction. Endogenous tissue inhibitors of metalloproteinases (TIMPs) reduce excessive proteolytic ECM degradation by MMPs. The balance between MMPs and TIMPs plays a major role in vascular remodeling, angiogenesis, and the uterine and systemic vasodilation during normal pregnancy. An imbalance in the MMPs/TIMPs activity ratio may underlie the pathogenesis of vascular diseases such as abdominal aortic aneurysm, varicose veins, hypertension and preeclampsia. Downregulation of MMPs using genetic manipulations of endogenous TIMPs, or synthetic pharmacological inhibitors such as BB-94 (Batimastat) and doxycycline, and Ro-28-2653, a more specific inhibitor of gelatinases and membrane type 1-MMP, could be beneficial in reducing the MMP-mediated vascular dysfunction and the progressive vessel wall damage associated with vascular disease. PMID:17678629

  17. Plasma β-amyloid in Alzheimer’s disease and vascular disease

    PubMed Central

    Janelidze, Shorena; Stomrud, Erik; Palmqvist, Sebastian; Zetterberg, Henrik; van Westen, Danielle; Jeromin, Andreas; Song, Linan; Hanlon, David; Tan Hehir, Cristina A.; Baker, David; Blennow, Kaj; Hansson, Oskar

    2016-01-01

    Implementation of amyloid biomarkers in clinical practice would be accelerated if such biomarkers could be measured in blood. We analyzed plasma levels of Aβ42 and Aβ40 in a cohort of 719 individuals (the Swedish BioFINDER study), including patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer’s disease (AD) dementia and cognitively healthy elderly, using a ultrasensitive immunoassay (Simoa platform). There were weak positive correlations between plasma and cerebrospinal fluid (CSF) levels for both Aβ42 and Aβ40, and negative correlations between plasma Aβ42 and neocortical amyloid deposition (measured with PET). Plasma levels of Aβ42 and Aβ40 were reduced in AD dementia compared with all other diagnostic groups. However, during the preclinical or prodromal AD stages (i.e. in amyloid positive controls, SCD and MCI) plasma concentration of Aβ42 was just moderately decreased whereas Aβ40 levels were unchanged. Higher plasma (but not CSF) levels of Aβ were associated with white matter lesions, cerebral microbleeds, hypertension, diabetes and ischemic heart disease. In summary, plasma Aβ is overtly decreased during the dementia stage of AD indicating that prominent changes in Aβ metabolism occur later in the periphery compared to the brain. Further, increased levels of Aβ in plasma are associated with vascular disease. PMID:27241045

  18. Is Pseudoexfoliation Syndrome a Risk Factor for Cerebro Vascular Disease?

    PubMed

    Kan, Emrah; Yılmaz, Ahmet; Demirağ, Mehmet Derya; Çalık, Murat

    2017-01-01

    To determine the relationship between cerebro vascular disease and pseudoexfoliation syndrome. This cross-sectional case control study consisted of 50 patients with ischemic-type cerebro vascular disease and 50 control subjects. All subjects were investigated for diabetes mellitus and hypertension status and underwent a detailed ophthalmic examination. A diagnosis of pseudoexfoliation syndrome was made if characteristic greyish particulate matter was found on the anterior lens capsule after pupillary dilatation by slit-lamp examination. All subjects were compared in terms of pseudoexfoliation syndrome, diabetes mellitus, and hypertension. Pearson Chi Square and Student's t test were used for statistical analysis. Logistic regression analyses of the risk factors between groups were also made. The presence of pseudoexfoliation syndrome was significantly higher in patients with cerebro vascular disease when compared to the control subjects (p = 0.02). The frequency of diabetes mellitus was similar between the two groups. Arterial hypertension was significantly more frequent in the patient group when compared to the control subjects (p < 0.01). The logistic regression analysis showed that both pseudoexfoliation syndrome and hypertension were significantly associated with cerebro vascular disease. In the present study, we found that pseudoexfoliation syndrome frequency was found to be higher in patients with cerebro vascular disease than in control subjects. A slit-lamp examination of the eye could be an important marker that indicates the risk of cerebro vascular disease. We recommend an evaluation of all subjects with pseudoexfoliation syndrome for the presence of cerebro vascular disease. Longitudinal studies with larger populations are needed to confirm this relationship.

  19. Treatment for cerebral small vessel disease: effect of relaxin on the function and structure of cerebral parenchymal arterioles during hypertension.

    PubMed

    Chan, Siu-Lung; Sweet, Julie G; Cipolla, Marilyn J

    2013-10-01

    We investigated the effect of hypertension on the function and structure of cerebral parenchymal arterioles (PAs), a major target of cerebral small vessel disease (SVD), and determined whether relaxin is a treatment for SVD during hypertension. PAs were isolated from 18-wk-old female normotensive Wistar-Kyoto (WKY) rats, spontaneous hypertensive rats (SHRs), and SHRs treated with human relaxin 2 for 14 d (4 μg/h; n=8/group) and studied using a pressurized arteriograph system. Hypertension reduced PA inner diameter (58±3 vs. 49±3 μm at 60 mmHg in WKY rats, P<0.05), suggesting inward remodeling that was reversed by relaxin (56±4 μm, P<0.05). Relaxin also increased PA distensibility in SHRs (34±2 vs. 10±2% in SHRs, P<0.05). Relaxin was detected in cerebrospinal fluid (110±30 pg/ml) after systemic administration, suggesting that it crosses the blood-brain barrier (BBB). Relaxin receptors (RXFP1/2) were not detected in cerebral vasculature, but relaxin increased vascular endothelial growth factor (VEGF) and matrix metalloproteinase 2 (MMP-2) expression in brain cortex. Inhibition of VEGF receptor tyrosine kinase (axitinib, 4 mg/kg/d, 14 d) had no effect on increased distensibility with relaxin, but caused outward hypertrophic remodeling of PAs from SHRs. These results suggest that relaxin crosses the BBB and activates MMP-2 in brain cortex, which may interact with PAs to increase distensibility. VEGF appears to be involved in remodeling of PAs, but not relaxin-induced increased distensibility.

  20. Brief Screening of Vascular Cognitive Impairment in Patients With Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Without Dementia

    PubMed Central

    Hollocks, Matthew J.; Tan, Rhea Y.Y.; Morris, Robin G.; Markus, Hugh S.

    2016-01-01

    Background and Purpose— Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic form of cerebral small vessel disease leading to early-onset stroke and dementia, with younger patients frequently showing subclinical deficits in cognition. At present, there are no targeted cognitive screening measures for this population. However, the Brief Memory and Executive Test (BMET) and the Montreal Cognitive Assessment (MoCA) have shown utility in detecting cognitive impairment in sporadic small vessel disease. This study assesses the BMET and the MoCA as clinical tools for detecting mild cognitive deficits in CADASIL. Methods— Sixty-six prospectively recruited patients with CADASIL, and 66 matched controls completed the BMET, with a subset of these also completing the MoCA. Receiver operating characteristic curves were calculated to examine the sensitivity and specificity of clinical cutoffs for the detection of vascular cognitive impairment and reduced activities of daily living. Results— Patients with CADASIL showed more cognitive impairment overall and were poorer on both executive/processing and memory indices of the BMET relative to controls. The BMET showed good accuracy in predicting vascular cognitive impairment (85% sensitivity and 84% specificity) and impaired instrumental activities of daily living (92% sensitivity and 77% specificity). The MoCA also showed good predictive validity for vascular cognitive impairment (80% sensitivity and 78% specificity) and instrumental activities of daily living (75% sensitivity and 76% specificity). The most important background predictor of vascular cognitive impairment was a history of stroke. Conclusions— The results indicate that the BMET and the MoCA are clinically useful and sensitive screening measures for early cognitive impairment in patients with CADASIL. PMID:27625375

  1. Brief Screening of Vascular Cognitive Impairment in Patients With Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Without Dementia.

    PubMed

    Brookes, Rebecca L; Hollocks, Matthew J; Tan, Rhea Y Y; Morris, Robin G; Markus, Hugh S

    2016-10-01

    Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic form of cerebral small vessel disease leading to early-onset stroke and dementia, with younger patients frequently showing subclinical deficits in cognition. At present, there are no targeted cognitive screening measures for this population. However, the Brief Memory and Executive Test (BMET) and the Montreal Cognitive Assessment (MoCA) have shown utility in detecting cognitive impairment in sporadic small vessel disease. This study assesses the BMET and the MoCA as clinical tools for detecting mild cognitive deficits in CADASIL. Sixty-six prospectively recruited patients with CADASIL, and 66 matched controls completed the BMET, with a subset of these also completing the MoCA. Receiver operating characteristic curves were calculated to examine the sensitivity and specificity of clinical cutoffs for the detection of vascular cognitive impairment and reduced activities of daily living. Patients with CADASIL showed more cognitive impairment overall and were poorer on both executive/processing and memory indices of the BMET relative to controls. The BMET showed good accuracy in predicting vascular cognitive impairment (85% sensitivity and 84% specificity) and impaired instrumental activities of daily living (92% sensitivity and 77% specificity). The MoCA also showed good predictive validity for vascular cognitive impairment (80% sensitivity and 78% specificity) and instrumental activities of daily living (75% sensitivity and 76% specificity). The most important background predictor of vascular cognitive impairment was a history of stroke. The results indicate that the BMET and the MoCA are clinically useful and sensitive screening measures for early cognitive impairment in patients with CADASIL. © 2016 The Authors.

  2. Differential effects of ischemic vascular disease and Alzheimer's disease on brain atrophy and cognition.

    PubMed

    Zheng, Ling; Vinters, Harry V; Mack, Wendy J; Weiner, Michael W; Chui, Helena C

    2016-01-01

    We previously reported that pathologic measures of arteriosclerosis (AS), cerebral infarction, and Alzheimer’s disease (AD) are independently correlated with cortical gray matter (CGM) atrophy measured by in vivo magnetic resonance imaging (MRI). Here, we use path analyses to model the associations between these three pathology measures and cognitive impairment, as mediated by CGM atrophy, after controlling for age and education. In this sample of 116 elderly persons followed longitudinally to autopsy (ischemic vascular disease (IVD) program project), differential patterns were observed between AS and atrophy/cognition versus AD and atrophy/cognition. The total effect of AD pathology on global cognition (β = -0.61, s.e. = 0.06) was four times stronger than that of AS (β = -0.15, s.e. = 0.08). The effect of AS on cognition appears to occur through cerebral infarction and CGM atrophy (β = -0.13, s.e. = 0.04). In contrast, the effects of AD pathology on global cognition (β = -0.50, s.e. = 0.07) occur through a direct pathway that is five times stronger than the indirect pathway acting through CGM atrophy (β = -0.09, s.e. = 0.03). The strength of this direct AD pathway was not significantly mitigated by adding hippocampal volume to the model. AD pathology affects cognition not only through brain atrophy, but also via an unmeasured pathway that could be related to synaptic dysfunction before the development of cortical atrophy.

  3. Differential effects of ischemic vascular disease and Alzheimer’s disease on brain atrophy and cognition

    PubMed Central

    Zheng, Ling; Vinters, Harry V; Mack, Wendy J; Weiner, Michael W

    2016-01-01

    We previously reported that pathologic measures of arteriosclerosis (AS), cerebral infarction, and Alzheimer’s disease (AD) are independently correlated with cortical gray matter (CGM) atrophy measured by in vivo magnetic resonance imaging (MRI). Here, we use path analyses to model the associations between these three pathology measures and cognitive impairment, as mediated by CGM atrophy, after controlling for age and education. In this sample of 116 elderly persons followed longitudinally to autopsy (ischemic vascular disease (IVD) program project), differential patterns were observed between AS and atrophy/cognition versus AD and atrophy/cognition. The total effect of AD pathology on global cognition (β = −0.61, s.e. = 0.06) was four times stronger than that of AS (β = −0.15, s.e. = 0.08). The effect of AS on cognition appears to occur through cerebral infarction and CGM atrophy (β = −0.13, s.e. = 0.04). In contrast, the effects of AD pathology on global cognition (β = −0.50, s.e. = 0.07) occur through a direct pathway that is five times stronger than the indirect pathway acting through CGM atrophy (β = −0.09, s.e. = 0.03). The strength of this direct AD pathway was not significantly mitigated by adding hippocampal volume to the model. AD pathology affects cognition not only through brain atrophy, but also via an unmeasured pathway that could be related to synaptic dysfunction before the development of cortical atrophy. PMID:26126864

  4. Platelets in the Alzheimer's disease brain: do they play a role in cerebral amyloid angiopathy?

    PubMed

    Kniewallner, Kathrin M; Ehrlich, Daniela; Kiefer, Andreas; Marksteiner, Josef; Humpel, Christian

    2015-01-01

    Alzheimer's disease (AD) is characterized by extracellular beta-amyloid plaques and intracellular tau tangles. AD-related pathology is often accompanied by vascular changes. The predominant vascular lesions in AD are cerebral amyloid angiopathy (CAA) and arteriosclerosis. Platelets circulate along the vessel wall responding immediately to vascular injury. The aim of the present study was to explore the presence and migration of platelets (thrombocytes) to sites of small vascular bleedings and/or to beta-amyloid plaques in the brain. We infused fluorescently labeled red PKH26 mouse platelets into transgenic Alzheimer mice overexpressing APP with Swedish/Dutch/Iowa mutations (APP_SDI) and explored if platelets migrate into the brain. Further we studied whether platelets accumulate in the vicinity of β-amyloid plaques. Our animal data shows that infused platelets are found in the liver and partly in the lung, while in the brain platelets were visible to a minor degree. In mice, we did not observe a significant association of platelets with beta-amyloid plaques or vessels. In the brain of Alzheimer postmortem patients platelets could be detected by immunohistochemistry for CD41 and CD62P, but the majority was found in vessels with or without beta-amyloid load, and only a few single platelets migrated deeper into the brain. Our findings suggest that platelets do not migrate into the brains of Alzheimer disease but are concentrated in brain vessels.

  5. Pulmonary vascular response of dogs with heartworm disease.

    PubMed Central

    Rawlings, C A

    1978-01-01

    Heartworm diseases in dogs is an infectious disease that produces pulmonary hypertension. Dogs with the early vascular changes of heartworm disease, but without the clinical cardiopulmonary signs and pulmonary hypertension, were studied. Dogs with early heartworm were identified that had an exaggerated hypertensive response to hypoxia and to postaglandin F2alpha as compared to those of normal dogs. The pulmonary hypertensive response of dogs with spontaneous heartworm disease varied widely between individuals. PMID:743600

  6. Pulmonary vascular response of dogs with heartworm disease.

    PubMed

    Rawlings, C A

    1978-10-01

    Heartworm diseases in dogs is an infectious disease that produces pulmonary hypertension. Dogs with the early vascular changes of heartworm disease, but without the clinical cardiopulmonary signs and pulmonary hypertension, were studied. Dogs with early heartworm were identified that had an exaggerated hypertensive response to hypoxia and to postaglandin F2alpha as compared to those of normal dogs. The pulmonary hypertensive response of dogs with spontaneous heartworm disease varied widely between individuals.

  7. Adiponectin as a potential biomarker of vascular disease

    PubMed Central

    Ebrahimi-Mamaeghani, Mehrangiz; Mohammadi, Somayeh; Arefhosseini, Seyed Rafie; Fallah, Parviz; Bazi, Zahra

    2015-01-01

    The increasing prevalence of diabetes and its complications heralds an alarming situation worldwide. Obesity-associated changes in circulating adiponectin concentrations have the capacity to predict insulin sensitivity and are a link between obesity and a number of vascular diseases. One obvious consequence of obesity is a decrease in circulating levels of adiponectin, which are associated with cardiovascular disorders and associated vascular comorbidities. Human and animal studies have demonstrated decreased adiponectin to be an independent risk factor for cardiovascular disease. However, in animal studies, increased circulating adiponectin alleviates obesity-induced endothelial dysfunction and hypertension, and also prevents atherosclerosis, myocardial infarction, and diabetic cardiac tissue disorders. Further, metabolism of a number of foods and medications are affected by induction of adiponectin. Adiponectin has beneficial effects on cardiovascular cells via its antidiabetic, anti-inflammatory, antioxidant, antiapoptotic, antiatherogenic, vasodilatory, and antithrombotic activity, and consequently has a favorable effect on cardiac and vascular health. Understanding the molecular mechanisms underlying the regulation of adiponectin secretion and signaling is critical for designing new therapeutic strategies. This review summarizes the recent evidence for the physiological role and clinical significance of adiponectin in vascular health, identification of the receptor and post-receptor signaling events related to the protective effects of the adiponectin system on vascular compartments, and its potential use as a target for therapeutic intervention in vascular disease. PMID:25653535

  8. Deviation from Optimal Vascular Caliber Control at Middle Cerebral Artery Bifurcations Harboring Aneurysms

    PubMed Central

    Baharoglu, Merih I.; Lauric, Alexandra; Wu, Chengyuan; Hippelheuser, James; Malek, Adel M.

    2014-01-01

    Cerebral aneurysms form preferentially at arterial bifurcations. The vascular optimality principle (VOP) decrees that minimal energy loss across bifurcations requires optimal caliber control between radii of parent (r0) and daughter branches (r1 and r2): r0n=r1n+r2n, with n approximating three. VOP entails constant wall shear stress (WSS), an endothelial phenotype regulator. We sought to determine if caliber control is maintained in aneurysmal intracranial bifurcations. Three-dimensional rotational angiographic volumes of 159 middle cerebral artery (MCA) bifurcations (62 aneurysmal) were processed using 3D gradient edge-detection filtering, enabling threshold-insensitive radius measurement. Radius ratio (RR)=r03/(r13+r23) and estimated junction exponent (n) were compared between aneurysmal and non-aneurysmal bifurcations using Student t-test and Wilcoxon rank-sum analysis. The results show that non-aneurysmal bifurcations display optimal caliber control with mean RR of 1.05 and median n of 2.84. In contrast, aneurysmal bifurcations had significantly lower RR (0.76, p<.0001) and higher n (4.28, p<.0001). Unexpectedly, 37% of aneurysmal bifurcations revealed a daughter branch larger than its parent vessel, an absolute violation of optimality, not witnessed in non-aneurysmal bifurcations. The aneurysms originated more often off the smaller daughter (52%) vs. larger daughter branch (16%). Aneurysm size was not statistically correlated to RR or n. Aneurysmal males showed higher deviation from VOP. Non-aneurysmal MCA bifurcations contralateral to aneurysmal ones showed optimal caliber control. Aneurysmal bifurcations, in contrast to non-aneurysmal counterparts, disobey the VOP and may exhibit dysregulation in WSS-mediated caliber control. The mechanism of this focal divergence from optimality may underlie aneurysm pathogenesis and requires further study. PMID:25242132

  9. miRNAs: roles and clinical applications in vascular disease.

    PubMed

    Jamaluddin, Md Saha; Weakley, Sarah M; Zhang, Lidong; Kougias, Panagiotis; Lin, Peter H; Yao, Qizhi; Chen, Changyi

    2011-01-01

    miRNAs are small, endogenously expressed noncoding RNAs that regulate gene expression, mainly at the post-transcriptional level, via degradation or translational inhibition of their target mRNAs. Functionally, an individual miRNA can regulate the expression of multiple target genes. The study of miRNAs is rapidly growing and recent studies have revealed a significant role of miRNAs in vascular biology and disease. Many miRNAs are highly expressed in the vasculature, and their expression is dysregulated in diseased vessels. Several miRNAs have been found to be critical modulators of vascular pathologies, such as atherosclerosis, lipoprotein metabolism, inflammation, arterial remodeling, angiogenesis, smooth muscle cell regeneration, hypertension, apoptosis, neointimal hyperplasia and signal transduction pathways. Thus, miRNAs may serve as novel biomarkers and/or therapeutic targets for vascular disease. This article summarizes the current studies related to the disease correlations and functional roles of miRNAs in the vascular system and discusses the potential applications of miRNAs in vascular disease.

  10. Brain metabolism in Alzheimer disease and vascular dementia assessed by in vivo proton magnetic resonance spectroscopy.

    PubMed

    Herminghaus, Sebastian; Frölich, Lutz; Gorriz, Corrina; Pilatus, Ullrich; Dierks, Thomas; Wittsack, Hans-Jörg; Lanfermann, Heinrich; Maurer, Konrad; Zanella, Friedhelm E

    2003-07-30

    Proton magnetic resonance spectroscopy (MRS) allows the assessment of various cerebral metabolites non-invasively in vivo. Among 1H MRS-detectable metabolites, N-acetyl-aspartate and N-acetyl-aspartyl-glutamate (tNAA), trimethylamines (TMA), creatine and creatine phosphate (tCr), inositol (Ins) and glutamate (Gla) are of particular interest, since these moieties can be assigned to specific neuronal and glial metabolic pathways, membrane constituents, and energy metabolism. In this study on 94 subjects from a memory clinic population, 1H MRS results (single voxel STEAM: TE 20 ms, TR 1500 ms) on the above metabolites were assessed for five different brain regions in probable vascular dementia (VD), probable Alzheimer's disease (AD), and age-matched healthy controls. In both VD and AD, ratios of tNAA/tCr were decreased, which may be attributed to neuronal atrophy and loss, and Ins/tCr-ratios were increased indicating either enhanced gliosis or alteration of the cerebral inositol metabolism. However, the topographical distribution of the metabolic alterations in both diseases differed, revealing a temporoparietal pattern for AD and a global, subcortically pronounced pattern for VD. Furthermore, patients suffering from vascular dementia (VD) had remarkably enhanced TMA/tCr ratios, potentially due to ongoing degradation of myelin. Thus, the metabolic alterations obtained by 1H MRS in vivo allow insights into the pathophysiology of the different dementias and may be useful for diagnostic classification.

  11. Detection of cerebral amyloid angiopathy by 3-T magnetic resonance imaging and amyloid positron emission tomography in a patient with subcortical ischaemic vascular dementia.

    PubMed

    Kida, Hirotaka; Satoh, Masayuki; Ii, Yuichiro; Fukuyama, Hidenao; Maeda, Masayuki; Tomimoto, Hidekazu

    2017-01-01

    The patient was an 81-year-old man who had been treated for hypertension for several decades. In 2012, he developed gait disturbance and mild amnesia. One year later, his gait disturbance worsened, and he developed urinary incontinence. Conventional brain magnetic resonance imaging using T 2 -weighted images and fluid-attenuated inversion recovery showed multiple lacunar infarctions. These findings fulfilled the diagnostic criteria for subcortical ischaemic vascular dementia. However, susceptibility weighted imaging showed multiple lobar microbleeds in the bilateral occipitoparietal lobes, and double inversion recovery and 3-D fluid-attenuated inversion recovery images on 3-T magnetic resonance imaging revealed cortical microinfarctions in the left parietal-temporo-occipito region. Pittsburgh compound B-positron emission tomography revealed diffuse uptake in the cerebral cortex. Therefore, we diagnosed the patient with subcortical ischaemic vascular dementia associated with Alzheimer's disease. The use of the double inversion recovery and susceptibility weighted imaging on 3-T magnetic resonance imaging may be a supplemental strategy for diagnosing cerebral amyloid angiopathy, which is closely associated with Alzheimer's disease.

  12. Possible role of vascular risk factors in Alzheimer's disease and vascular dementia.

    PubMed

    Hasnain, Mehrul; Vieweg, W Victor R

    2014-01-01

    The contribution of vascular risk factors to Alzheimer-vascular spectrum dementias is increasingly being recognized. We provide an overview of recent literature on this subject. Overweight and obesity as well as underweight during midlife predict cognitive decline and dementia later in life. Hypertension during midlife is also associated with dementia later in life and the association is stronger for untreated hypertension. Calcium channel blockers, angiotensin converting enzyme inhibitors, and angiotensin-1 receptor-blockers may be particularly beneficial in diminishing the risk of dementia associated with hypertension. Studies have fairly consistently shown that type 2 diabetes is a risk factor for dementia. Episodes of hypoglycemia add to this risk. Regular physical exercise during any point in the lifespan protects against cognitive decline and dementia. Most benefit is realized with physical exercise during early and midlife. Dyslipidemia also increases the risk of dementia but the findings are less consistent. Findings on the possible benefit of lipid-lowering agents (statins) are conflicting. Earlier studies identified smoking as protective of dementia but recent better designed studies have consistently shown that smoking increases the risk of dementia. The association of vascular risk factors with dementia is more robust for vascular dementia than Alzheimer's disease. Heterogeneity of studies and lack of trials specifically designed to assess cognition as an endpoint make firm conclusions difficult. But considering the expected global burden of dementia and projected attributable risk of vascular risk factors to it, there is sufficient evidence to promote vascular risk factor reduction strategies as dementia prevention interventions.

  13. Thermolabile MTHFR genotype and retinal vascular occlusive disease

    PubMed Central

    Cahill, M; Karabatzaki, M; Donoghue, C; Meleady, R; Mynett-Johnson, L; Mooney, D; Graham, I; Whitehead, A; Shields, D

    2001-01-01

    BACKGROUND—Raised levels of total plasma homocysteine (tHcy) are associated with an increased risk of retinal vascular occlusive disease. A thermolabile form of a pivotal enzyme in homocysteine metabolism, methylenetetrahydrofolate reductase (MTHFR), has been associated with vascular occlusive disease and raised tHcy levels. The relation between thermolabile MTHFR genotype, tHcy, and retinal vascular occlusive disease has not been determined.
METHODS—A retrospective case-control study involving hospital based controls and cases with retinal vascular occlusions in whom tHcy levels had been determined was undertaken. Genotyping for the MTHFR 677 C-T mutation that specifies the thermolabile form of the enzyme was performed by established methods in all subjects. The relation between homozygosity for thermolabile MTHFR genotype (TT), raised tHcy levels, and risk of retinal vascular occlusive disease was examined.
RESULTS—87 cases of retinal vascular occlusive disease (mean age 68.7 years) comprising 26 cases of retinal artery occlusion and 61 of retinal vein occlusion were compared with 87 controls (mean age 70.2 years). The TT genotype did not confer a significantly increased risk of retinal vascular occlusive disease. The mean tHcy level was significantly higher in the cases than in the controls (p<0.0001). Overall, and in both the cases and controls, the frequency of the TT genotype was higher in those with normal tHcy levels than in those with increased levels of tHcy. However, the TT genotype did not significantly alter the risk of increased tHcy levels in these patients.
CONCLUSIONS—The TT genotype is not associated with an increased risk of retinal vascular occlusive disease or increased tHcy levels in this group of elderly patients. In older patients, nutritional rather than genetic factors may be more important in increasing tHcy levels, a known risk factor for retinal vascular occlusive disease.

 PMID:11133719

  14. Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

    PubMed

    Khalil, Raouf A

    2013-12-15

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Estrogen, Vascular Estrogen Receptor and Hormone Therapy in Postmenopausal Vascular Disease

    PubMed Central

    Khalil, Raouf A.

    2013-01-01

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women’s Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject’s age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. PMID:24099797

  16. Vascular endothelial growth factor improves recovery of sensorimotor and cognitive deficits after focal cerebral ischemia in the rat.

    PubMed

    Wang, Yaoming; Galvan, Veronica; Gorostiza, Olivia; Ataie, Marina; Jin, Kunlin; Greenberg, David A

    2006-10-18

    Vascular endothelial growth factor (VEGF) is an angiogenesis factor with neurotrophic, neuroprotective and neuroproliferative effects. Depending on the dose, route and time of administration in relation to focal cerebral ischemia, VEGF can improve histological outcome and sensorimotor function in rodents. However, VEGF also increases vascular permeability, which can lead to brain edema and exacerbate ischemic brain injury. Thus, although VEGF is a candidate therapeutic for stroke and other ischemic disorders, its benefit relative to risk is uncertain. Considering that functional rather than histological measures of outcome are probably most relevant to therapeutic prospects for human stroke, we investigated the effects of VEGF after middle cerebral artery occlusion in rats using a series of behavioral tests. We report that VEGF improves functional outcome in ischemic rats, including both sensorimotor and cognitive deficiencies.

  17. Mutation of FOXC1 and PITX2 induces cerebral small-vessel disease

    PubMed Central

    French, Curtis R.; Seshadri, Sudha; Destefano, Anita L.; Fornage, Myriam; Arnold, Corey R.; Gage, Philip J.; Skarie, Jonathan M.; Dobyns, William B.; Millen, Kathleen J.; Liu, Ting; Dietz, William; Kume, Tsutomu; Hofker, Marten; Emery, Derek J.; Childs, Sarah J.; Waskiewicz, Andrew J.; Lehmann, Ordan J.

    2014-01-01

    Patients with cerebral small-vessel disease (CSVD) exhibit perturbed end-artery function and have an increased risk for stroke and age-related cognitive decline. Here, we used targeted genome-wide association (GWA) analysis and defined a CSVD locus adjacent to the forkhead transcription factor FOXC1. Moreover, we determined that the linked SNPs influence FOXC1 transcript levels and demonstrated that patients as young as 1 year of age with altered FOXC1 function exhibit CSVD. MRI analysis of patients with missense and nonsense mutations as well as FOXC1-encompassing segmental duplication and deletion revealed white matter hyperintensities, dilated perivascular spaces, and lacunar infarction. In a zebrafish model, overexpression or morpholino-induced suppression of foxc1 induced cerebral hemorrhage. Inhibition of foxc1 perturbed platelet-derived growth factor (Pdgf) signaling, impairing neural crest migration and the recruitment of mural cells, which are essential for vascular stability. GWA analysis also linked the FOXC1-interacting transcription factor PITX2 to CSVD, and both patients with PITX2 mutations and murine Pitx2–/– mutants displayed brain vascular phenotypes. Together, these results extend the genetic etiology of stroke and demonstrate an increasing developmental basis for human cerebrovascular disease. PMID:25250569

  18. Early Detection System of Vascular Disease and Its Application Prospect

    PubMed Central

    2016-01-01

    Markers of imaging, structure, and function reflecting vascular damage, integrating a long time accumulation effect of traditional and unrecognized cardiovascular risk factors, can be regarded as surrogate endpoints of target organ damage before the occurrence of clinical events. Prevention of cardiovascular disease requires risk stratification and treatment of traditional risk factors, such as smoking, hypertension, hyperlipidemia, and diabetes. However, traditional risk stratification is not sufficient to provide accurate assessment of future cardiovascular events. Therefore, vascular injury related parameters obtained by ultrasound or other noninvasive devices, as a surrogate parameter of subclinical cardiovascular disease, can improve cardiovascular risk assessment and optimize the preventive treatment strategy. Thus, we will summarize the research progress and clinical application of early assessment technology of vascular diseases in the present review. PMID:28042567

  19. Vascular wall progenitor cells in health and disease.

    PubMed

    Psaltis, Peter J; Simari, Robert D

    2015-04-10

    The vasculature plays an indispensible role in organ development and maintenance of tissue homeostasis, such that disturbances to it impact greatly on developmental and postnatal health. Although cell turnover in healthy blood vessels is low, it increases considerably under pathological conditions. The principle sources for this phenomenon have long been considered to be the recruitment of cells from the peripheral circulation and the re-entry of mature cells in the vessel wall back into cell cycle. However, recent discoveries have also uncovered the presence of a range of multipotent and lineage-restricted progenitor cells in the mural layers of postnatal blood vessels, possessing high proliferative capacity and potential to generate endothelial, smooth muscle, hematopoietic or mesenchymal cell progeny. In particular, the tunica adventitia has emerged as a progenitor-rich compartment with niche-like characteristics that support and regulate vascular wall progenitor cells. Preliminary data indicate the involvement of some of these vascular wall progenitor cells in vascular disease states, adding weight to the notion that the adventitia is integral to vascular wall pathogenesis, and raising potential implications for clinical therapies. This review discusses the current body of evidence for the existence of vascular wall progenitor cell subpopulations from development to adulthood and addresses the gains made and significant challenges that lie ahead in trying to accurately delineate their identities, origins, regulatory pathways, and relevance to normal vascular structure and function, as well as disease. © 2015 American Heart Association, Inc.

  20. Diabetic Retinopathy: Vascular and Inflammatory Disease

    PubMed Central

    Semeraro, F.; Cancarini, A.; dell'Omo, R.; Rezzola, S.; Romano, M. R.; Costagliola, C.

    2015-01-01

    Diabetic retinopathy (DR) is the leading cause of visual impairment in the working-age population of the Western world. The pathogenesis of DR is complex and several vascular, inflammatory, and neuronal mechanisms are involved. Inflammation mediates structural and molecular alterations associated with DR. However, the molecular mechanisms underlying the inflammatory pathways associated with DR are not completely characterized. Previous studies indicate that tissue hypoxia and dysregulation of immune responses associated with diabetes mellitus can induce increased expression of numerous vitreous mediators responsible for DR development. Thus, analysis of vitreous humor obtained from diabetic patients has made it possible to identify some of the mediators (cytokines, chemokines, and other factors) responsible for DR pathogenesis. Further studies are needed to better understand the relationship between inflammation and DR. Herein the main vitreous-related factors triggering the occurrence of retinal complication in diabetes are highlighted. PMID:26137497

  1. Are vascular factors involved in Alzheimer's disease? Facts and theories.

    PubMed

    Di Iorio, A; Zito, M; Lupinetti, M; Abate, G

    1999-12-01

    The hypothesis that vascular factors may contribute to the development of Alzheimer's disease (AD) is supported by epidemiologic and pathologic observations. Arterial hypertension and diabetes have been found to be associated not only with vascular dementia, but also with AD; in addition, the treatment of hypertension with calcium antagonists seems to prevent degenerative dementias. Hypertension and hyperinsulinemia favor the deposition of amyloid substance in the brain. The histopathology of AD is marked not only by neurofibrillary tangles and senile plaques, but also by macro and micro congophilic angiopathy and ischemic white matter rarefaction. The specific AD pathological lesions, if isolated, are not able to lead to an evident clinical picture of dementia, which, on the contrary, becomes evident when vascular, mainly subcortical, lesions are associated. These and other observations suggest that vascular factors may have a role in the development of AD. An aggressive approach to these factors could be of value in the prevention of AD.

  2. Impact of apocynin on vascular disease in hypertension.

    PubMed

    Virdis, Agostino; Gesi, Marco; Taddei, Stefano

    2016-12-01

    Reactive oxygen species (ROS) are generated by cell metabolism of oxygen and represent signaling molecules playing an active role in vascular biology. In pathological conditions, including hypertension, a ROS excess, together with reduced endogenous antioxidant defenses, occurs, determining a state of oxidative stress. NAD(P)H oxidase (Nox) is a major ROS source within the vasculature. A large body of literature has demonstrated that hypertension-associated vascular functional and structural changes are attributable to Nox-driven intravascular ROS generation. Apocynin is a methoxy-catechol discovered as an inhibitor of superoxide. It has been utilized in several laboratories and in different models of hypertension as an inhibitor of Nox. Recent evidence proposes that apocynin predominantly acts as an antioxidant. The present review will discuss the role of ROS in vascular disease in hypertension and the impact of apocynin on these vascular changes. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Alcohol-induced apoptosis of canine cerebral vascular smooth muscle cells: role of extracellular and intracellular calcium ions.

    PubMed

    Li, Wenyan; Li, Jianfeng; Liu, Weiming; Altura, Bella T; Altura, Burton M

    2004-01-16

    Exposure of canine cerebral vascular smooth muscle cells (VSMCs) to ethanol (10, 25 and 100 mM) for 1, 3 and 5 days induced apoptosis with its typical characteristics of nuclear shrinkage, condensation, and DNA breakage as well as formation of apoptotic bodies observed by fluorescence staining, terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling and comet assays. Such effects of alcohol on cerebral VSMCs were time- and concentration-dependent. The threshold ethanol concentration for induction of the apoptotic process was found to be 10 mM. Extracellular and intracellular Ca2+ chelators, i.e. ethylglycol-bisbeta-aminoethylether-N,N,N'N'-tetraacetic acid (EGTA, 5 mM) and 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetra-acetic acid AM (BAPTA, 10(-6) M), respectively, ameliorated greatly the number of cerebral VSMCs which underwent apoptosis. Verapamil, however, failed to inhibit apoptosis of cerebral VSMCs. From these new findings, we suggest that alcohol-induced apoptosis may contribute to alcohol-induced brain-vascular damage and stroke. In addition, our findings point to potential caution for humans who imbibe two or more standard drinks per day or who undergo 'binge drinking'.

  4. Determinants of human cerebral pressure–flow velocity relationships: new insights from vascular modelling and Ca2+ channel blockade

    PubMed Central

    Tzeng, Yu-Chieh; Chan, Gregory S H; Willie, Christopher K; Ainslie, Philip N

    2011-01-01

    Abstract The fundamental determinants of human dynamic cerebral autoregulation are poorly understood, particularly the role of vascular compliance and the myogenic response. We sought to 1) determine whether capacitive blood flow associated with vascular compliance and driven by the rate of change in mean arterial blood pressure (dMAP/dt) is an important determinant of middle cerebral artery velocity (MCAv) dynamics and 2) characterise the impact of myogenic blockade on these cerebral pressure–flow velocity relations in humans. We measured MCAv and mean arterial pressure (MAP) during oscillatory lower body negative pressure (n = 8) at 0.10 and 0.05 Hz before and after cerebral Ca2+ channel blockade (nimodipine). Pressure–flow velocity relationships were characterised using transfer function analysis and a regression-based Windkessel analysis that incorporates MAP and dMAP/dt as predictors of MCAv dynamics. Results show that incorporation of dMAP/dt accounted for more MCAv variance (R2 0.80–0.99) than if only MAP was considered (R2 0.05–0.90). The capacitive gain relating dMAP/dt and MCAv was strongly correlated to transfer function gain (0.05 Hz, r = 0.93, P < 0.01; 0.10 Hz, r = 0.91, P < 0.01), but not to phase or coherence. Ca2+ channel blockade increased the conductive gain relation between MAP and MCAv (P < 0.05), and reduced phase at 0.05 Hz (P < 0.01). Capacitive and transfer function gain were unaltered. The findings suggest capacitive blood flow is an important determinant of cerebral haemodynamics that bears strong relations to some metrics of dynamic cerebral autoregulation derived from transfer function analysis, and that Ca2+ channel blockade enhances pressure-driven resistive blood flow but does not alter capacitive blood flow. PMID:21540346

  5. An intelligent support system for automatic detection of cerebral vascular accidents from brain CT images.

    PubMed

    Hajimani, Elmira; Ruano, M G; Ruano, A E

    2017-07-01

    This paper presents a Radial Basis Functions Neural Network (RBFNN) based detection system, for automatic identification of Cerebral Vascular Accidents (CVA) through analysis of Computed Tomographic (CT) images. For the design of a neural network classifier, a Multi Objective Genetic Algorithm (MOGA) framework is used to determine the architecture of the classifier, its corresponding parameters and input features by maximizing the classification precision, while ensuring generalization. This approach considers a large number of input features, comprising first and second order pixel intensity statistics, as well as symmetry/asymmetry information with respect to the ideal mid-sagittal line. Values of specificity of 98% and sensitivity of 98% were obtained, at pixel level, by an ensemble of non-dominated models generated by MOGA, in a set of 150 CT slices (1,867,602pixels), marked by a NeuroRadiologist. This approach also compares favorably at a lesion level with three other published solutions, in terms of specificity (86% compared with 84%), degree of coincidence of marked lesions (89% compared with 77%) and classification accuracy rate (96% compared with 88%). Copyright © 2017. Published by Elsevier B.V.

  6. Renal vascular disease in neurofibromatosis type 2: association or coincidence?

    PubMed

    Cordeiro, Nuno J V; Gardner, Kate R; Huson, Susan M; Stewart, Helen; Elston, John S; Howard, Emma L; Tullus, Kjell O; Pike, Michael G

    2006-01-01

    Neurofibromatosis type 2 (NF2) remains a challenging diagnosis in childhood where there may be no neurological involvement. A 12-month-old male in whom NF2 was suspected because of characteristic ophthalmological and cutaneous lesions is reported. Cranial MRI showed no tumours. A pathogenic mutation was identified on NF2 gene analysis. The child developed hypertension due to renal vascular disease. Although renal vascular disease is a recognized complication of neurofibromatosis type 1 (NF1), it has not been reported in NF2.

  7. Vascular contributions to cognitive impairment and dementia including Alzheimer's disease.

    PubMed

    Snyder, Heather M; Corriveau, Roderick A; Craft, Suzanne; Faber, James E; Greenberg, Steven M; Knopman, David; Lamb, Bruce T; Montine, Thomas J; Nedergaard, Maiken; Schaffer, Chris B; Schneider, Julie A; Wellington, Cheryl; Wilcock, Donna M; Zipfel, Gregory J; Zlokovic, Berislav; Bain, Lisa J; Bosetti, Francesca; Galis, Zorina S; Koroshetz, Walter; Carrillo, Maria C

    2015-06-01

    Scientific evidence continues to demonstrate the linkage of vascular contributions to cognitive impairment and dementia such as Alzheimer's disease. In December, 2013, the Alzheimer's Association, with scientific input from the National Institute of Neurological Disorders and Stroke and the National Heart, Lung and Blood Institute from the National Institutes of Health, convened scientific experts to discuss the research gaps in our understanding of how vascular factors contribute to Alzheimer's disease and related dementia. This manuscript summarizes the meeting and the resultant discussion, including an outline of next steps needed to move this area of research forward. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  8. Applications of Doppler ultrasound in clinical vascular disease

    NASA Technical Reports Server (NTRS)

    Barnes, R. W.; Hokanson, D. E.; Sumner, D. S.; Strandness, D. E., Jr.

    1975-01-01

    Doppler ultrasound has become the most useful and versatile noninvasive technique for objective evaluation of clinical vascular disease. Commercially available continuous-wave instruments provide qualitative and quantitative assessment of venous and arterial disease. Pulsed Doppler ultrasound was developed to provide longitudinal and transverse cross-sectional images of the arterial lumen with a resolution approaching that of conventional X-ray techniques. Application of Doppler ultrasound in venous, peripheral arterial, and cerebrovascular diseases is reviewed.

  9. Applications of Doppler ultrasound in clinical vascular disease

    NASA Technical Reports Server (NTRS)

    Barnes, R. W.; Hokanson, D. E.; Sumner, D. S.; Strandness, D. E., Jr.

    1975-01-01

    Doppler ultrasound has become the most useful and versatile noninvasive technique for objective evaluation of clinical vascular disease. Commercially available continuous-wave instruments provide qualitative and quantitative assessment of venous and arterial disease. Pulsed Doppler ultrasound was developed to provide longitudinal and transverse cross-sectional images of the arterial lumen with a resolution approaching that of conventional X-ray techniques. Application of Doppler ultrasound in venous, peripheral arterial, and cerebrovascular diseases is reviewed.

  10. Differential impact of serum total bilirubin level on cerebral atherosclerosis and cerebral small vessel disease

    PubMed Central

    Kim, Jonguk; Yoon, Seung-Jae; Woo, Min-Hee; Kim, Sang-Heum; Kim, Nam-Keun; Kim, Jinkwon; Kim, OK-Joon; Oh, Seung-Hun

    2017-01-01

    Background A low serum total bilirubin (T-bil) level is associated with an increased risk of atherosclerosis. However, the differential impact of the serum T-bil level on cerebral atherosclerosis and cerebral small vessel disease (SVD) is still unclear. Methods We evaluated serum T-bil levels from 1,128 neurologically healthy subjects. Indices of cerebral atherosclerosis (extracranial arterial stenosis [ECAS] and intracranial arterial stenosis [ICAS]), and indices of SVD (silent lacunar infarct [SLI], and moderate-to-severe white matter hyperintensities [msWMH]) were evaluated by the use of brain magnetic resonance imaging (MRI) and MR angiography. Results In logistic regression analysis after adjusting for confounding variables, subjects within middle T-bil (odds ratio [OR]: 0.63; 95% CI: 0.41–0.97) and high T-bil tertiles (OR: 0.54; 95% CI: 0.33–0.86) showed a lower prevalence of ECAS than those in a low T-bil tertile. Although subjects with a high T-bil tertile had a lower prevalence of ICAS than those with a low T-bil tertile, the statistical significance was marginal after adjusting for confounding variables. There were no significant differences in the proportions of subjects with SLI and msWMH across serum T-bil tertile groups. Conclusions The serum T-bil level is negatively associated with cerebral atherosclerosis, especially extracranial atherosclerosis, but not with SVD. PMID:28319156

  11. Vascular disease in mice with a dysfunctional circadian clock

    PubMed Central

    Anea, Ciprian B.; Zhang, Maoxiang; Stepp, David W.; Bryan Simkins, G.; Reed, Guy; Fulton, David J.; Daniel Rudic, R.

    2009-01-01

    Background Cardiovascular disease is the leading cause of death for both men and women in the United States and the world. There is a profound pattern in the time of day at which the death occurs; it is in the morning, when the endothelium is most vulnerable and blood pressure surges, that stroke and heart attack most frequently happen. Though the molecular components of circadian rhythms rhythmically oscillate in blood vessels, evidence of a direct function for the ‘circadian clock’ in the progression to vascular disease is lacking. Methods and Results In the current study, we have found increased pathological remodeling and vascular injury in mice with aberrant circadian rhythms, Bmal1 (Bmal1-KO) and Clock (Clockmut). In addition, naïve aortae from Bmal1-KO and Clock mutant mice exhibit endothelial dysfunction. Akt and subsequent nitric oxide signalling—a pathway critical to vascular function—was significantly attenuated in arteries from Bmal1-KO mice. Conclusions Our data reveals a new role for the circadian clock during chronic vascular responses which may be of significance in the progression of vascular disease. PMID:19273720

  12. Effects of dietary manipulation on vascular status of patients with peripheral vascular disease.

    PubMed

    Hutchinson, K; Oberle, K; Crockford, P; Grace, M; Whyte, L; Gee, M; Williams, T; Brown, G

    1983-06-24

    In a one-year, double-blind clinical trial, 45 patients with peripheral vascular disease (PVD) were randomly assigned to either the American Heart Association Hyperlipidemia Diet C (n = 20) or a low-fat, high-fiber, complex carbohydrate diet similar to the Pritikin Maintenance Diet (n = 25). Vascular status and blood lipid levels were monitored at 0, 2, 4, 6, and 12 months. Walking distance increased significantly in both groups, with no difference between groups. No vascular parameters changed significantly, suggesting that increased walking distance was due to improved metabolic capacity of the muscle. A trend toward lower blood lipid values was observed, with no significant differences within or between groups. We conclude that while patients with PVD benefit from a program of diet and exercise, there is no apparent advantage to the more difficult complex carbohydrate diet.

  13. Protein Kinase C Inhibitors as Modulators of Vascular Function and Their Application in Vascular Disease

    PubMed Central

    Khalil, Raouf A.

    2013-01-01

    Blood pressure (BP) is regulated by multiple neuronal, hormonal, renal and vascular control mechanisms. Changes in signaling mechanisms in the endothelium, vascular smooth muscle (VSM) and extracellular matrix cause alterations in vascular tone and blood vessel remodeling and may lead to persistent increases in vascular resistance and hypertension (HTN). In VSM, activation of surface receptors by vasoconstrictor stimuli causes an increase in intracellular free Ca2+ concentration ([Ca2+]i), which forms a complex with calmodulin, activates myosin light chain (MLC) kinase and leads to MLC phosphorylation, actin-myosin interaction and VSM contraction. Vasoconstrictor agonists could also increase the production of diacylglycerol which activates protein kinase C (PKC). PKC is a family of Ca2+-dependent and Ca2+-independent isozymes that have different distributions in various blood vessels, and undergo translocation from the cytosol to the plasma membrane, cytoskeleton or the nucleus during cell activation. In VSM, PKC translocation to the cell surface may trigger a cascade of biochemical events leading to activation of mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK), a pathway that ultimately increases the myofilament force sensitivity to [Ca2+]i, and enhances actin-myosin interaction and VSM contraction. PKC translocation to the nucleus may induce transactivation of various genes and promote VSM growth and proliferation. PKC could also affect endothelium-derived relaxing and contracting factors as well as matrix metalloproteinases (MMPs) in the extracellular matrix further affecting vascular reactivity and remodeling. In addition to vasoactive factors, reactive oxygen species, inflammatory cytokines and other metabolic factors could affect PKC activity. Increased PKC expression and activity have been observed in vascular disease and in certain forms of experimental and human HTN. Targeting of vascular PKC using PKC inhibitors may function in concert with

  14. Protein Kinase C Inhibitors as Modulators of Vascular Function and their Application in Vascular Disease.

    PubMed

    Khalil, Raouf A

    2013-01-01

    Blood pressure (BP) is regulated by multiple neuronal, hormonal, renal and vascular control mechanisms. Changes in signaling mechanisms in the endothelium, vascular smooth muscle (VSM) and extracellular matrix cause alterations in vascular tone and blood vessel remodeling and may lead to persistent increases in vascular resistance and hypertension (HTN). In VSM, activation of surface receptors by vasoconstrictor stimuli causes an increase in intracellular free Ca(2+) concentration ([Ca(2+)]i), which forms a complex with calmodulin, activates myosin light chain (MLC) kinase and leads to MLC phosphorylation, actin-myosin interaction and VSM contraction. Vasoconstrictor agonists could also increase the production of diacylglycerol which activates protein kinase C (PKC). PKC is a family of Ca(2+)-dependent and Ca(2+)-independent isozymes that have different distributions in various blood vessels, and undergo translocation from the cytosol to the plasma membrane, cytoskeleton or the nucleus during cell activation. In VSM, PKC translocation to the cell surface may trigger a cascade of biochemical events leading to activation of mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK), a pathway that ultimately increases the myofilament force sensitivity to [Ca(2+)]i, and enhances actin-myosin interaction and VSM contraction. PKC translocation to the nucleus may induce transactivation of various genes and promote VSM growth and proliferation. PKC could also affect endothelium-derived relaxing and contracting factors as well as matrix metalloproteinase (MMPs) in the extracellular matrix further affecting vascular reactivity and remodeling. In addition to vasoactive factors, reactive oxygen species, inflammatory cytokines and other metabolic factors could affect PKC activity. Increased PKC expression and activity have been observed in vascular disease and in certain forms of experimental and human HTN. Targeting of vascular PKC using PKC inhibitors may function in

  15. Patients with advanced Parkinson's disease with and without freezing of gait: a comparative analysis of vascular lesions using brain MRI.

    PubMed

    Gallardo, M J; Cabello, J P; Pastor, C; Muñoz-Torrero, J J; Carrasco, S; Ibañez, R; Vaamonde, J

    2014-05-01

    Freezing of gait (FOG) is one of the most disabling and enigmatic symptoms in Parkinson's disease. Vascular lesions, observed in magnetic resonance imaging (MRI) scans, may produce or exacerbate this symptom. The study includes 22 patients with Parkinson's disease subjects, 12 with freezing of gait and 10 without. All patients underwent an MRI scan and any vascular lesions were analysed using the modified Fazekas scale. Patients with FOG scored higher on the modified Fazekas scale than the rest of the group. Although the two groups contained the same percentage of patients with vascular lesions (50% in both groups), lesion load was higher in the group of patients with FOG. Vascular lesions in the periventricular area and deep white matter seem to be the most involved in the development of FOG. Vascular lesions may contribute to the onset or worsening of FOG in patients with PD. This study suggests that cerebral vascular disease should be considered in patients with FOG. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  16. Peripheral vascular disease as remote ischemic preconditioning, for acute stroke.

    PubMed

    Connolly, Mark; Bilgin-Freiert, Arzu; Ellingson, Benjamin; Dusick, Joshua R; Liebeskind, David; Saver, Jeff; Gonzalez, Nestor R

    2013-10-01

    Remote ischemic preconditioning (RIPC) is a powerful endogenous mechanism whereby a brief period of ischemia is capable of protecting remote tissues from subsequent ischemic insult. While this phenomenon has been extensively studied in the heart and brain in animal models, little work has been done to explore the effects of RIPC in human patients with acute cerebral ischemia. This study investigates whether chronic peripheral hypoperfusion, in the form of pre-existing arterial peripheral vascular disease (PVD) that has not been surgically treated, is capable of inducing neuroprotective effects for acute ischemic stroke. Individuals with PVD who had not undergone prior surgical treatment were identified from a registry of stroke patients. A control group within the same database was identified by matching patient's demographics and risk factors. The two groups were compared in terms of outcome by NIH Stroke Scale (NIHSS), modified Rankin scale (mRS), mortality, and volume of infarcted tissue at presentation and at discharge. The matching algorithm identified 26 pairs of PVD-control patients (9 pairs were female and 17 pairs were male). Age range was 20-93 years (mean 73). The PVD group was found to have significantly lower NIHSS scores at admission (NIHSS≤4: PVD 47.1%, control 4.35%, p<0.003), significantly more favorable outcomes at discharge (mRS≤2: PVD 30.8%, control 3.84%, p<0.012), and a significantly lower mortality rate (PVD 26.9%, control 57.7%, p=0.024). Mean acute stroke volume at admission and at discharge were significantly lower for the PVD group (admission: PVD 39.6 mL, control 148.3 mL, p<0.005 and discharge: PVD 111.7 mL, control 275 mL, p<0.001). Chronic limb hypoperfusion induced by PVD can potentially produce a neuroprotective effect in acute ischemic stroke. This effect resembles the neuroprotection induced by RIPC in preclinical models. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Cerebral Small Vessel Disease and Motoric Cognitive Risk Syndrome: Results from the Kerala-Einstein Study.

    PubMed

    Wang, Nan; Allali, Gilles; Kesavadas, Chandrasekharan; Noone, Mohan L; Pradeep, Vayyattu G; Blumen, Helena M; Verghese, Joe

    2016-01-01

    The contribution of cerebral small vessel disease to cognitive decline, especially in non-Caucasian populations, is not well established. We examined the relationship between cerebral small vessel disease and motoric cognitive risk syndrome (MCR), a recently described pre-dementia syndrome, in Indian seniors. 139 participants (mean age 66.6 ± 5.4 y, 33.1% female) participating in the Kerala-Einstein study in Southern India were examined in a cross-sectional study. The presence of cerebral small vessel disease (lacunar infarcts and cerebral microbleeds (CMB)) and white matter hyperintensities on MRI was ascertained by raters blinded to clinical information. MCR was defined by the presence of cognitive complaints and slow gait in older adults without dementia or mobility disability. Thirty-eight (27.3%) participants met MCR criteria. The overall prevalence of lacunar infarcts and CMB was 49.6% and 9.4% , respectively. Lacunar infarcts in the frontal lobe, but no other brain regions, were associated with MCR even after adjusting for vascular risk factors and presence of white matter hyperintensities (adjusted Odds Ratio (aOR): 4.67, 95% CI: 1.69-12.94). Frontal lacunar infarcts were associated with slow gait (aOR: 3.98, 95% CI: 1.46-10.79) and poor performance on memory test (β: -1.24, 95% CI: -2.42 to -0.05), but not with cognitive complaints or non-memory tests. No association of CMB was found with MCR, individual MCR criterion or cognitive tests. Frontal lacunar infarcts are associated with MCR in Indian seniors, perhaps, by contributing to slow gait and poor memory function.

  18. Management of retinal vascular diseases: a patient-centric approach.

    PubMed

    Brand, C S

    2012-04-01

    Retinal vascular diseases are a leading cause of blindness in the Western world. Advancement in the clinical management of these diseases has been fast-paced, with new treatments becoming available as well as license extensions of existing treatments. Vascular endothelial growth factor (VEGF) has been implicated in certain retinal vascular diseases, including wet age-related macular degeneration (AMD), diabetic macular oedema (DMO), and retinal vein occlusion (RVO). Treatment of wet AMD and visual impairment due to either DMO or macular oedema secondary to RVO with an anti-VEGF on an as needed basis, rather than a fixed schedule, allows an individualised treatment approach; providing treatment when patients are most likely to benefit from it, while minimising the number of unnecessary intravitreal injections. Thus, an individualised treatment regimen reduces the chances of over-treatment and under-treatment, optimising both the risk/benefit profile of the treatment and the efficient use of NHS resource. Streamlining of treatment for patients with wet AMD and visual impairment due to either DMO or macular oedema secondary to RVO, by using one treatment with similar posology across all three diseases, may help to minimise burden of clinic capacity and complexity and hence optimise patient outcomes. Informed treatment decisions and efficient clinic throughput are important for optimal patient outcomes in the fast-changing field of retinal vascular diseases.

  19. Use of sulodexide in patients with peripheral vascular disease.

    PubMed

    Lasierra-Cirujeda, J; Coronel, P; Aza, Mj; Gimeno, M

    2010-01-01

    Sulodexide is a highly purified glycosaminoglycan containing a combination of heparan sulfate with affinity for antithrombin III and dermatan sulfate with affinity for heparin cofactor II. This antithrombotic and antithrombin activity is of great pharmacologic interest and makes sulodexide a suitable drug for the prophylaxis and treatment of arterial and venous peripheral diseases. In arterial pathology, changes in the Winsor Index, improvement in peripheral blood flow, and reduction in pain-free walking distance confirm that treatment with oral sulodexide is effective. Lipid components linked to the genesis of peripheral vascular processes, including triglycerides, total cholesterol, and low-density lipoprotein fractions, as well as plasma and blood viscosity, are reduced by the administration of sulodexide, whereas the high-density lipoprotein fraction increases. Sulodexide inhibits aggregation and adhesion of platelets at the level of the vascular wall, reduces plasma fibrinogen concentrations, reduces plasminogen activator inhibitor-1, and increases tissue plasminogen activator, as well as systemic fibrinolytic and thrombolytic activity, thereby demonstrating efficacy in the treatment of thromboembolic disease. There is no interaction between sulodexide and other drugs used as long-term treatment for peripheral vascular disease. It is well tolerated, and the adverse reactions described after oral administration are related mainly to transient gastrointestinal intolerance, ie, nausea, dyspepsia, and minor bowel symptoms. Sulodexide may become the treatment of choice when dealing with vascular diseases and their complications, as well as for the prevention of venous thromboembolic disease, being particularly indicated in elderly patients, due to its good tolerability and ease of management.

  20. [Current advances in spinal vascular disease].

    PubMed

    Yano, Shunsuke; Hida, Kazutoshi

    2009-06-01

    During treatment of spinal arteriovenous malformations (AVMs), such as dural arteriovenous fistula (AVF), perimedullary AVF, and intramedullary AVM, it is often difficult to identify the feeding artery and draining vein because of presence of multiple dilated veins in the dural space and multiple shunts. Disruption of incorrect vessels may elicit major functional deficits in the spinal cord. To avoid such complications, it is extremely important to identify the correct vessels prior to and during surgical treatment. Recently, several types of techniques have been developed for diagnosis and treatment of spinal AVMs. Although spinal AVMs must be diagnosed by digital subtraction angiography (DSA) before any surgical treatment can begin, other techniques such as CT angiography and contrasted MR angiography are valuable as a form of screening and can be useful in guiding the DSA procedure. In addition, several techniques including intraoperative angiography, dye-injection and the micro Doppler method have proven useful during the surgical procedure for understanding complex spinal vascular architectures. These approaches facilitate in the identification of feeding vessels, thereby preventing neurological deterioration due to disruption of the incorrect vessels during the surgery of spinal AVF. At the neurophysiological level, intraoperative MEP monitoring is a sensitive method for the detection of immediate motor fiber damage. Utilization of these innovative approaches will contribute to the safe and effective treatment of spinal AVMs.

  1. Mechanisms of stroke in sickle cell disease: sickle erythrocytes decrease cerebral blood flow in rats after nitric oxide synthase inhibition.

    PubMed

    French, J A; Kenny, D; Scott, J P; Hoffmann, R G; Wood, J D; Hudetz, A G; Hillery, C A

    1997-06-15

    The etiology of stroke in sickle cell disease is unclear, but may involve abnormal red blood cell (RBC) adhesion to the vascular endothelium and altered vasomotor tone regulation. Therefore, we examined both the adhesion of sickle (SS)-RBCs to cerebral microvessels and the effect of SS-RBCs on cerebral blood flow when the nitric oxide (NO) pathway was inhibited. The effect of SS-RBCs was studied in the rat cerebral microcirculation using either a cranial window for direct visualization of infused RBCs or laser Doppler flowmetry (LDF) to measure RBC flow. When fluorescently labeled human RBCs were infused into rats, SS-RBCs had increased adhesion to rat cerebral microvessels compared with control AA-RBCs (P = .01). Next, washed SS-RBCs or AA-RBCs were infused into rats prepared with LDF probes after pretreatment (40 mg/kg intravenously) with the NO synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), or the control isomer, D-NAME. In 9 rats treated with systemic L-NAME and SS-RBCs, 5 of 9 experienced a significant decrease in LDF and died within 30 minutes after the RBC infusion (P = .0012). In contrast, all control groups completed the experiment with stable LDF and hemodynamics. Four rats received a localized superfusion of L-NAME (1 mmol/L) through the cranial window followed by infusion of SS-RBCs. Total cessation of flow in all observed cerebral microvessels occurred in 3 of 4 rats within 15 minutes after infusion of SS-RBCs. We conclude that the NO pathway is critical in maintaining cerebral blood flow in the presence of SS-RBCs in this rat model. In addition, the enhanced adhesion of SS-RBCs to rat brain microvessels may contribute to cerebral vaso-occlusion either directly, by disrupting blood flow, or indirectly, by disturbing the vascular endothelium.

  2. [Vascular risk factors and Alzheimer disease risk: epidemiological studies review].

    PubMed

    Cowppli-Bony, Pascale; Dartigues, Jean-François; Orgogozo, Jean-Marc

    2006-03-01

    Etiology of Alzheimer's disease (AD) is still undefined in its most frequent sporadic type, but a role of vascular risk factor is more and more evocated in its pathophysiology. This role enables to hope that preventive or curative care of vascular risk factors could decrease AD incidence. Among these factors, high blood pressure, diabetes, hypercholesterolemia and tobacco consumption were the most studied. We review the risk for AD, which had been associated with each of these factors in epidemiological studies. High blood pressure is associated with an increased risk of AD in most studies while the results are more controversial for the others factors. All these four vascular risk factors have variable interaction with the presence of cerebrovascular diseases and of the epsilon 4 allele of the apolipoprotein E gene which is a predisposition factor for sporadic AD.

  3. Evaluation and percutaneous management of atherosclerotic peripheral vascular disease

    SciTech Connect

    Widlus, D.M.; Osterman, F.A. Jr. )

    1989-06-02

    Atherosclerotic peripheral vascular disease (PVD) of the lower extremities deprives a person of the ability to exercise to their satisfaction, later of the ability to perform the activities of their daily life, and finally of their legs themselves. Peripheral vascular disease has long been managed by the vascular surgeon utilizing endarterectomy and peripheral arterial bypass. Patient acceptance of nonsurgical, percutaneous procedures such as percutaneous transluminal balloon angioplasty (PTA) is high. Increased utilization of these procedures has led to improved techniques and adjuncts to therapy, as well as more critical review of long-term results. This article will review the evaluation and nonoperative management of PVD, with an emphasis on the newer modalities of management presently being investigated.

  4. Silent Cerebral Small Vessel Disease in Restless Legs Syndrome

    PubMed Central

    Ferri, Raffaele; Cosentino, Filomena I.I.; Moussouttas, Michael; Lanuzza, Bartolo; Aricò, Debora; Bagai, Kanika; Wang, Lily; McLaughlin, BethAnn; Walters, Arthur S.

    2016-01-01

    Study Objectives: Growing literature suggests that patients with restless legs syndrome (RLS) may be at increased risk for hypertension, heart disease, and stroke. Cerebral small vessel disease (SVD) is a known risk factor for clinical stroke. This study evaluated silent cerebral SVD by MRI in patients with RLS, in the absence of a history of previous clinical stroke or known stroke risk factors and taking into account disease duration. Methods: Fifty-three patients with RLS < 10 y were prospectively recruited along with 44 with RLS > 10 y and 74 normal controls. A magnetic resonance imaging study was obtained from all subjects and scans were analyzed for area and volume of SVD. Results: There was a significant increase in SVD area in the entire group of RLS patients compared to controls (P = 0.036); this was almost entirely driven by the group with RLS > 10 y. SVD area and volume were significantly increased in patients with RLS > 10 y with respect to both controls (P < 0.0001 and P < 0.0014, respectively) and RLS < 10 y (P < 0.00022 and P < 0.003, respectively). Age, duration of RLS, and the interaction of age and duration of RLS were independent predictors of SVD disease. Duration of RLS was an independent predictor of the burden of cerebral SVD (area P < 0.00012 and volume P < 0.0025), whereas sex and insomnia were not. Conclusion: RLS duration should be taken into account when analyzing the association between RLS and cerebrovascular disease; our data support the hypothesis that a long-lasting RLS and its accompanying periodic limb movements in sleep are a risk factor for silent SVD and perhaps for the development of clinical stroke. Citation: Ferri R, Cosentino FI, Moussouttas M, Lanuzza B, Aricò D, Bagai K, Wang L, McLaughlin B, Walters AS. Silent cerebral small vessel disease in restless legs syndrome. SLEEP 2016;39(7):1371–1377. PMID:27091527

  5. Contribution of neuroimaging to the diagnosis of Alzheimer's disease and vascular dementia.

    PubMed

    Román, Gustavo; Pascual, Belén

    2012-11-01

    The aim of this study was to review, summarize and analyze recent findings relevant to the contribution of neuroimaging to the diagnosis of Alzheimer's disease (AD) and vascular dementia (VaD). Computerized tomography (CT) or magnetic resonance imaging (MRI) provide accurate demonstration of the location and rate of progression of atrophic changes affecting the brain in AD and the different types of vascular lesions observed in mixed dementias and in pure VaD. Quantification of cortical thickness allows early diagnosis and rate of progression from mild cognitive impairment (MCI) to dementia. White matter involvement can also be quantified with diffusion tensor imaging (DTI) and functional methods including fMRI, functional connectivity, and MR spectroscopy (MRS). Isotope-based techniques such as positron emission tomography (PET) allow measurement of regional cerebral glucose metabolism using (18)F-2-fluoro-deoxy-D-glucose (FDG). Cerebral blood flow can be measured using PET with H(2)(15)O or with single photon emission computerized tomography (SPECT) with technetium ((99m)Tc-HMPAO) or, more recently, arterial spin label (ASL) imaging. There are isotope markers for amyloid-beta ((11)O-PIB, (18)F-florbetapir), tau ((18)FDDNP) and activated microglia ((11)C-PK11195). Neuroimaging markers are particularly useful at the early symptomatic and preclinical asymptomatic phases of AD, as well as serving as endpoints in clinical trials.

  6. Vascular function, cerebral cortical thickness, and cognitive performance in middle-aged Hispanic and non-Hispanic Caucasian adults.

    PubMed

    Pasha, Evan P; Kaur, Sonya S; Gonzales, Mitzi M; Machin, Daniel R; Kasischke, Kennon; Tanaka, Hirofumi; Haley, Andreana P

    2015-04-01

    Hispanics are at increased risk for acquiring cardiovascular risk factors that contribute to cognitive dysfunction. To compare indices of vascular health with measures of cerebral gray matter integrity, 60 middle-aged Hispanic and non-Hispanic Caucasian participants were matched across age, sex, years of education, and mental status. Arterial stiffness was characterized by β-stiffness index and carotid-femoral pulse wave velocity, and magnetic resonance imaging estimated cortical thickness in a priori regions of interest known to be susceptible to vascular risk factors. Measures of arterial stiffness were significantly higher in Hispanics than in non-Hispanic Caucasians. Hispanics exhibited thinner left inferior frontal gyrus (LIFG) cortical thickness (P=.04) with concurrently lower language (P=.02), memory (P=.03), and attention-executive functioning (P=.02). These results suggest that compromised vascular health may occur simultaneously with cortical thinning of the LIFG as an early neuropathological alteration in Hispanics.

  7. Atlas-based method for segmentation of cerebral vascular trees from phase-contrast magnetic resonance angiography

    NASA Astrophysics Data System (ADS)

    Passat, Nicolas; Ronse, Christian; Baruthio, Joseph; Armspach, Jean-Paul; Maillot, Claude; Jahn, Christine

    2004-05-01

    Phase-contrast magnetic resonance angiography (PC-MRA) can produce phase images which are 3-dimensional pictures of vascular structures. However, it also provides magnitude images, containing anatomical - but no vascular - data. Classically, algorithms dedicated to PC-MRA segmentation detect the cerebral vascular tree by only working on phase images. We propose here a new approach for segmentation of cerebral blood vessels in PC-MRA using both types of images. This approach is based on the hypothesis that a magnitude image contains anatomical information useful for vascular structures detection. That information can then be transposed from a normal case to any patient image by image registration. An atlas of the whole head has been developed in order to store such anatomical knowledge. It divides a magnitude image into several "vascular areas", each one having specific vessel properties. The atlas can be applied on any magnitude image of an entire or nearly entire head by deformable matching, thus helping to segment blood vessels from the associated phase image. The segmentation method used afterwards is composed of a topology-conserving region growing algorithm using adaptative threshold values depending on the current region of the atlas. This algorithm builds the arterial and venous trees by iteratively adding voxels which are selected according to their greyscale value and the variation of values in their neighborhood. The topology conservation is guaranteed by only selecting simple points during the growing process. The method has been performed on 15 PC-MRA's of the brain. The results have been validated using MIP and 3D surface rendering visualization; a comparison to other results obtained without an atlas proves that atlas-based methods are an effective way to optimize vascular segmentation strategies.

  8. Language Impairment in Alzheimer's Disease and Vascular Dementia.

    ERIC Educational Resources Information Center

    Lempinen, Maire; And Others

    A study of 21 patients with Alzheimer's Disease and 25 with vascular dementia, the two most common forms of dementia, investigated language impairments in the dementia syndrome to see if analysis of language disturbances is helpful in differential diagnosis. Diagnostic assessment included a neurological examination, detailed medical history,…

  9. Language Impairment in Alzheimer's Disease and Vascular Dementia.

    ERIC Educational Resources Information Center

    Lempinen, Maire; And Others

    A study of 21 patients with Alzheimer's Disease and 25 with vascular dementia, the two most common forms of dementia, investigated language impairments in the dementia syndrome to see if analysis of language disturbances is helpful in differential diagnosis. Diagnostic assessment included a neurological examination, detailed medical history,…

  10. Evidence of endothelial dysfunction in the development of Alzheimer’s disease: Is Alzheimer’s a vascular disorder?

    PubMed Central

    Kelleher, Rory J; Soiza, Roy L

    2013-01-01

    The etiology of Alzheimer’s disease (AD) remains unclear. The emerging view is that cerebrovascular dysfunction is a feature not only of cerebrovascular diseases, such as stroke, but also of neurodegenerative conditions, such as AD. In AD, there is impaired structure and function of cerebral blood vessels and cells in the neurovascular unit. These effects are mediated by vascular oxidative stress. Injury to the neurovascular unit alters cerebral blood flow regulation, depletes vascular reserves, disrupts the blood-brain barrier and reduces the brain’s repair capacity. Such injury can exacerbate the cognitive dysfunction exerted by incident ischemia and coexisting neurodegeneration. This article summarises data regarding cardiovascular risk factors, vascular abnormalities and brain endothelial damage in AD. In view of accumulating evidence of vascular pathology in AD, we also review the literature (MEDLINE, EMBASE) for clinical evidence of impaired endothelial function in AD. A total of 15 articles investigating endothelial dysfunction in AD were identified. 10 of these articles showed impaired endothelial function in AD patients. The current literature suggests endothelial dysfunction may be involved in the pathogenesis of AD. This aspect of AD pathology is particularly interesting in view of its potential for therapeutic intervention. Future research on endothelial function in AD should concentrate on population-based analysis and combine multiple methods to evaluate endothelial function. PMID:24224133

  11. Chronic depression as a model disease for cerebral aging.

    PubMed

    Bewernick, Bettina H; Schlaepfer, Thomas E

    2013-03-01

    Conceptualizations of the underlying neurobiology of major depression have changed their focus from dysfunctions of neurotransmission to dysfunctions of neurogenesis and neuroprotection. The "neurogenesis hypothesis of depression" posits that changes in the rate of neurogenesis are the underlying mechanism in the pathology and treatment of major depression. Stress, neuroinflammation, dysfunctional insulin regulation, oxidative stress, and alterations in neurotrophic factors possibly contribute to the development of depression. The influence of antidepressant therapies, namely pharmacotherapy and neuroprotectants, on cellular plasticity are summarized. A dysfunction of complex neuronal networks as a consequence of neural degeneration in neuropsychiatric diseases has led to the application of deep brain stimulation. We discuss the way depression seen in the light of the neurogenesis hypothesis can be used as a model disease for cerebral aging. A common pathological mechanism in depression and cerebral aging-a dysfunction of neuroprotection and neurogenesis-is discussed. This has implications for new treatment methods.

  12. Diabetes mellitus is a coronary heart disease risk equivalent for peripheral vascular disease.

    PubMed

    Newman, Jonathan D; Rockman, Caron B; Kosiborod, Mikhail; Guo, Yu; Zhong, Hua; Weintraub, Howard S; Schwartzbard, Arthur Z; Adelman, Mark A; Berger, Jeffrey S

    2017-02-01

    Diabetes mellitus (diabetes) is associated with significantly increased risk of peripheral vascular disease. Diabetes is classified as a coronary heart disease (CHD) risk equivalent, but it is unknown whether diabetes is a CHD risk equivalent for peripheral vascular disease. The objective was to evaluate the odds of peripheral arterial disease (PAD) or carotid artery stenosis (CAS) among participants with diabetes, CHD, or both, compared with participants without diabetes or CHD, in a nationwide vascular screening database. We hypothesized that diabetes and CHD would confer similar odds of PAD and CAS.

  13. The vascular contribution to Alzheimer’s disease

    PubMed Central

    Altman, Robin; Rutledge, John C.

    2010-01-01

    AD (Alzheimer’s disease) is a progressive neurodegenerative disease of unknown origin. Despite questions as to the underlying cause(s) of this disease, shared risk factors for both AD and atherosclerotic cardiovascular disease indicate that vascular mechanisms may critically contribute to the development and progression of both AD and atherosclerosis. An increased risk of developing AD is linked to the presence of the apoE4 (apolipoprotein E4) allele, which is also strongly associated with increased risk of developing atherosclerotic cardiovascular disease. Recent studies also indicate that cardiovascular risk factors, including elevated blood cholesterol and triacylglycerol (triglyceride), increase the likelihood of AD and vascular dementia. Lipids and lipoproteins in the circulation interact intimately with the cerebrovasculature, and may have important effects on its constituent brain microvascular endothelial cells and the adjoining astrocytes, which are components of the neurovascular unit. The present review will examine the potential mechanisms for understanding the contributions of vascular factors, including lipids, lipoproteins and cerebrovascular Aβ (amyloid β), to AD, and suggest therapeutic strategies for the attenuation of this devastating disease process. Specifically, we will focus on the actions of apoE, TGRLs (triacylglycerol-rich lipoproteins) and TGRL lipolysis products on injury of the neurovascular unit and increases in blood–brain barrier permeability. PMID:20684749

  14. Blood brain barrier breakdown as the starting point of cerebral small vessel disease? - New insights from a rat model

    PubMed Central

    2013-01-01

    Cerebral small vessel disease (CSVD, cerebral microangiopathy) leads to dementia and stroke-like symptoms. Lacunes, white matter lesions (WML) and microbleeds are the main pathological correlates depicted in in-vivo imaging diagnostics. Early studies described segmental arterial wall disorganizations of small penetrating cerebral arteries as the most pronounced underlying histopathology of lacunes. Luminal narrowing caused by arteriolosclerosis was supposed to result in hypoperfusion with WML and infarcts. We have used the model of spontaneously hypertensive stroke-prone rats (SHRSP) for a longitudinal study to elucidate early histological changes in small cerebral vessels. We suggest that endothelial injuries lead to multiple sites with blood brain barrier (BBB) leakage which cause an ongoing damage of the vessel wall and finally resulting in vessel ruptures and microbleeds. These microbleeds together with reactive small vessel occlusions induce overt cystic infarcts of the surrounding parenchyma. Thus, multiple endothelial leakage sites seem to be the starting point of cerebral microangiopathy. The vascular system reacts with an activated coagulatory state to these early endothelial injuries and by this induces the formation of stases, accumulations of erythrocytes, which represent the earliest detectable histological peculiarity of small vessel disease in SHRSP. In this review we focus on the meaning of the BBB breakdown in CSVD and finally discuss possible consequences for clinicians. PMID:23497521

  15. Vascular integrin immunoreactivity is selectively lost on capillaries during rat focal cerebral ischemia and reperfusion.

    PubMed

    Burggraf, Dorothe; Trinkl, Andreas; Burk, Jan; Martens, Helge K; Dichgans, Martin; Hamann, Gerhard F

    2008-01-16

    The alpha1-integrin cell adhesion molecules, the principal endothelial receptors for basal lamina (BL) components disappear during transient ischemia. The current study investigated the localization of integrins, the time dependency and vessel size selectivity in the normal rat brain before and after 3 h of cerebral ischemia (I3) and reperfusion (R). Additionally we looked for a correlation to the amount of extravasation and hemorrhage. In the normal brain, there was a clear immunoreactivity for the alpha1, alpha6, and beta1 integrins on the endothelial perivascular cells. After I3 followed by variable reperfusion intervals of 0, 9, and 24 h (R0, R9 and R24; respectively), the number of vessels and staining intensity indicating immunoreactivity in the ischemic area were compared with the contralateral side. The number of the beta1-immunoreactive capillaries was steadily decreasing with the reperfusion time: -12+/-5%, -15+/-7% and -43+/-8% at I3R0, I3R9 and I3R24 (all p<0.05). The beta1-staining intensity decreased homogeneously to -21% at I3R24 (p<0.05). Vascular staining for alpha1 was affected similarly. Interestingly, the alpha6-positive arterioles/venules were also reduced by -21% at I3R24 (p<0.05) in a diameter-selective way on vessels with diameters larger than 15 mum. The correlated break-down of the blood-brain-barrier was demonstrated by the significant rise of the extravasation of BSA from the perfusion solution as well as the increased hemorrhage after MCAO/R (hemoglobin: 103+/-4% versus 330+/-17%; BSA 101+/-3% versus 132+/-9% in I0R0 and I3R24, respectively). The prominent capillary vulnerability contributes significantly to the impairment of the microvascular integrity and after ischemia and reperfusion.

  16. Changes in cerebral vascular reactivity and structure following prolonged exposure to high altitude in humans.

    PubMed

    Foster, Glen E; Davies-Thompson, Jodie; Dominelli, Paolo B; Heran, Manraj K S; Donnelly, Joseph; duManoir, Gregory R; Ainslie, Philip N; Rauscher, Alexander; Sheel, A William

    2015-12-01

    Although high-altitude exposure can lead to neurocognitive impairment, even upon return to sea level, it remains unclear the extent to which brain volume and regional cerebral vascular reactivity (CVR) are altered following high-altitude exposure. The purpose of this study was to simultaneously determine the effect of 3 weeks at 5050 m on: (1) structural brain alterations; and (2) regional CVR after returning to sea level for 1 week. Healthy human volunteers (n = 6) underwent baseline and follow-up structural and functional magnetic resonance imaging (MRI) at rest and during a CVR protocol (end-tidal PCO2 reduced by -10, -5 and increased by +5, +10, and +15 mmHg from baseline). CVR maps (% mmHg(-1)) were generated using BOLD MRI and brain volumes were estimated. Following return to sea level, whole-brain volume and gray matter volume was reduced by 0.4 ± 0.3% (P < 0.01) and 2.6 ± 1.0% (P < 0.001), respectively; white matter was unchanged. Global gray matter CVR and white matter CVR were unchanged following return to sea level, but CVR was selectively increased (P < 0.05) in the brainstem (+30 ± 12%), hippocampus (+12 ± 3%), and thalamus (+10 ± 3%). These changes were the result of improvement and/or reversal of negative CVR to positive CVR in these regions. Three weeks of high-altitude exposure is reflected in loss of gray matter volume and improvements in negative CVR. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  17. Genetic determinants of obesity and related vascular diseases.

    PubMed

    Winter, Yaroslav; Sankowski, Roman; Back, Tobias

    2013-01-01

    Obesity is one of the major risk factors of vascular diseases, and its prevalence is increasing worldwide. In the past decade, progress has been made in the understanding of genetic determinants of obesity and obesity-associated diseases. Genome-wide association studies identified a number of genetic variants associated with obesity. In addition to common variants, FTO and MC4R, new loci, such as TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2, and NEGR1 have been detected. In the past years, abdominal obesity has been shown to be a more important vascular risk factor than the body mass index. In the context of vascular risk assessment, identification of genetic polymorphisms associated with accumulation of visceral fat is of special importance. Some polymorphisms associated with abdominal obesity, such as variants of gene encoding microsomal triglyceride transfer protein, have been already discovered. In this chapter, we provide a review of genetic determinants of obesity and discuss their role in obesity-related vascular diseases.

  18. Epilepsy: unusual presentation of cerebral hydatid disease in Children

    PubMed Central

    Hajhouji, Farouk; Aniba, Khalid; Laghmari, Mehdi; Lmejjati, Mohammed; Ghannane, Houssine; Benali, Said Ait

    2016-01-01

    Cerebral hydatid disease is very rare, representing only 2% of all cerebral space occupying lesions even in the countries where the disease is endemic. Intracranial hydatid cysts are more common in children and occur more frequently in the supratentorial space. The aim of this paper is to describe the characteristic features of computed tomography (CT) and magnetic resonance imaging (MRI), and to determine the clinical presentation and surgical outcome of cerebral hydatid disease. A 7-year-old girl was admitted to the emergency department because of an epileptic attack. On radiological examination a round, cystic lesion appeared in the parietal lobe and caused shift of the midline structures. The cyst was successfully removed using the dowling technique. The postoperative period was uneventful and seizures were not seen during follow up. Hydatid cyst of the brain presents clinically as intracranial space occupying lesion and is more common in children, it is well demonstrated by CT and MR examinations, and Surgery is the treatment option with affordable morbidity and low mortality.

  19. Life-long aerobic exercise preserved baseline cerebral blood flow but reduced vascular reactivity to CO2.

    PubMed

    Thomas, Binu P; Yezhuvath, Uma S; Tseng, Benjamin Y; Liu, Peiying; Levine, Benjamin D; Zhang, Rong; Lu, Hanzhang

    2013-11-01

    To examine the potential benefits of life-long aerobic exercise on brain health, in particular cerebrovascular function. Ten Masters athletes (MA) (seven males, three females; 74.5 ± 5.8 years) and 10 sedentary elderly individuals (SE) (eight males, two females; 75.4 ± 5.6 years) were recruited and baseline cerebral blood flow (CBF) and cerebral vascular reactivity (CVR) to CO2 were measured on a 3T MRI scanner. Nine sedentary young subjects were also recruited to serve as a control group to verify the age effect. When compared to the SE group, MA showed higher CBF in posterior cingulate cortex/precuneus, which are key regions of the default-mode-network and are known to be highly sensitive to age and dementia. CVR in the MA brains were paradoxically lower than that in SE. This effect was present throughout the brain. Within the MA group, individuals with higher VO2max had an even lower CVR, suggesting a dose-response relationship. Life-long aerobic exercise preserved blood supply in the brain's default-mode-network against age-related degradation. On the other hand, its impact on the cerebral vascular system seems to be characterized by a dampening of CO2 reactivity, possibly because of desensitization effects due to a higher lifetime exposure. Copyright © 2013 Wiley Periodicals, Inc.

  20. Bile pigments in pulmonary and vascular disease.

    PubMed

    Ryter, Stefan W

    2012-01-01

    The bile pigments, biliverdin, and bilirubin, are endogenously derived substances generated during enzymatic heme degradation. These compounds have been shown to act as chemical antioxidants in vitro. Bilirubin formed in tissues circulates in the serum, prior to undergoing hepatic conjugation and biliary excretion. The excess production of bilirubin has been associated with neurotoxicity, in particular to the newborn. Nevertheless, clinical evidence suggests that mild states of hyperbilirubinemia may be beneficial in protecting against cardiovascular disease in adults. Pharmacological application of either bilirubin and/or its biological precursor biliverdin, can provide therapeutic benefit in several animal models of cardiovascular and pulmonary disease. Furthermore, biliverdin and bilirubin can confer protection against ischemia/reperfusion injury and graft rejection secondary to organ transplantation in animal models. Several possible mechanisms for these effects have been proposed, including direct antioxidant and scavenging effects, and modulation of signaling pathways regulating inflammation, apoptosis, cell proliferation, and immune responses. The practicality and therapeutic-effectiveness of bile pigment application to humans remains unclear.

  1. Association Between Subclinical Cardiac Biomarkers and Clinically Manifest Cardiac Diseases With Cortical Cerebral Microinfarcts.

    PubMed

    Hilal, Saima; Chai, Yuek Ling; van Veluw, Susanne; Shaik, Muhammad Amin; Ikram, Mohammad Kamran; Venketasubramanian, Narayanaswamy; Richards, Arthur Mark; Biessels, Geert Jan; Chen, Christopher

    2017-04-01

    Subclinical and clinical cardiac diseases have been previously linked to magnetic resonance imaging (MRI) manifestations of cerebrovascular disease, such as lacunes and white matter hyperintensities, as well as dementia. Cortical cerebral microinfarcts (CMIs), a novel MRI marker of cerebral vascular disease, have not been studied, to date, in relation to subclinical and clinical cardiac diseases. To examine the association of blood biomarkers of subclinical cardiac disease and clinically manifest cardiac diseases with CMIs graded on 3-T MRI in a memory clinic population. This baseline cross-sectional analysis of a cohort study performed from August 12, 2010, to July 28, 2015, included 464 memory clinic participants. All participants underwent collection of blood samples, neuropsychological assessment, and 3-T MRI. N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) concentrations were measured by electrochemiluminescence immunoassays. Cardiac disease was defined as a history of atrial fibrillation, ischemic heart diseases, or congestive heart failure. The CMIs were graded according to a previously validated protocol. Of 464 participants, 124 had insufficient blood plasma samples and 97 had no CMI grading (none, incomplete, or ungradable MRI), leaving a sample size of 243 for final analysis (mean [SD] age, 72.8 [9.1] years; 116 men [42.9%]). Seventy participants (28.8%) had cortical CMIs (median, 1; range, 0-43). Compared with participants with no CMIs, those with CMIs had a significantly higher prevalence of atrial fibrillation (rate ratio [RR], 1.62; 95% CI, 1.20-21.8), ischemic heart disease (RR, 4.31; 95% CI, 3.38-5.49), and congestive heart failure (RR, 2.05; 95% CI, 1.29-3.25). Significantly higher levels of NT-proBNP (RR, 3.16; 95% CI, 2.33-4.27) and hs-cTnT (RR, 2.17; 95% CI, 1.00-4.74) were found in participants with CMIs. In multivariate models adjusted for demographics and vascular risk factors, higher

  2. Pulmonary vascular disease in a rabbit a high altitude

    NASA Astrophysics Data System (ADS)

    Heath, Donald; Williams, David; Rios-Datenz, Jaime; Gosney, John

    1990-03-01

    A male weanling rabbit of the New Zealand White strain, born and living at an altitude of 3800 m in La Paz, Bolivia, developed right ventricular hypertrophy. This was found to be associated with growth of vascular smooth muscle cells in the intima of pulmonary arterioles, and contrasted with muscularization of the walls of pulmonary arterioles, without extension into the intima, found in a healthy, high-altitude control rabbit of the same strain. A low-altitude control showed no such muscularization. It is concluded that alveolar hypoxia, acting directly or through an intermediate agent, is a growth factor for vascular smooth muscle cells in pulmonary arterioles. This is the first report of pulmonary vascular disease due to high altitude in rabbits.

  3. Information entropy-based fitting of the disease trajectory of brain ischemia-induced vascular cognitive impairment★

    PubMed Central

    Liu, Lin; Huo, Ju; Zhao, Ying; Tian, Yu

    2012-01-01

    The present study investigated the disease trajectory of vascular cognitive impairment using the entropy of information in a neural network mathematical simulation based on the free radical and excitatory amino acids theories. Glutamate, malondialdehyde, and inducible nitric oxide synthase content was significantly elevated, but acetylcholine, catalase, superoxide dismutase, glutathione peroxidase and constitutive nitric oxide synthase content was significantly decreased in our vascular cognitive impairment model. The fitting curves for each factor were obtained using Matlab software. Nineteen, 30 and 49 days post ischemia were the main output time frames of the influence of these seven factors. Our results demonstrated that vascular cognitive impairment involves multiple factors. These factors include excitatory amino acid toxicity and nitric oxide toxicity. These toxicities disrupt the dynamic equilibrium of the production and removal of oxygen free radicals after cerebral ischemia, reducing the ability to clear oxygen free radicals and worsening brain injury. PMID:25745466

  4. Inherited neurovascular diseases affecting cerebral blood vessels and smooth muscle.

    PubMed

    Sam, Christine; Li, Fei-Feng; Liu, Shu-Lin

    2015-10-01

    Neurovascular diseases are among the leading causes of mortality and permanent disability due to stroke, aneurysm, and other cardiovascular complications. Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Marfan syndrome are two neurovascular disorders that affect smooth muscle cells through accumulation of granule and osmiophilic materials and defective elastic fiber formations respectively. Moyamoya disease, hereditary hemorrhagic telangiectasia (HHT), microcephalic osteodysplastic primordial dwarfism type II (MOPD II), and Fabry's disease are disorders that affect the endothelium cells of blood vessels through occlusion or abnormal development. While much research has been done on mapping out mutations in these diseases, the exact mechanisms are still largely unknown. This paper briefly introduces the pathogenesis, genetics, clinical symptoms, and current methods of treatment of the diseases in the hope that it can help us better understand the mechanism of these diseases and work on ways to develop better diagnosis and treatment.

  5. Response of the sensorimotor cortex of cerebral palsy rats receiving transplantation of vascular endothelial growth factor 165-transfected neural stem cells.

    PubMed

    Tan, Jielu; Zheng, Xiangrong; Zhang, Shanshan; Yang, Yujia; Wang, Xia; Yu, Xiaohe; Zhong, Le

    2014-10-01

    Neural stem cells are characterized by the ability to differentiate and stably express exogenous ge-nes. Vascular endothelial growth factor plays a role in protecting local blood vessels and neurons of newborn rats with hypoxic-ischemic encephalopathy. Transplantation of vascular endothelial growth factor-transfected neural stem cells may be neuroprotective in rats with cerebral palsy. In this study, 7-day-old Sprague-Dawley rats were divided into five groups: (1) sham operation (control), (2) cerebral palsy model alone or with (3) phosphate-buffered saline, (4) vascular endothelial growth factor 165 + neural stem cells, or (5) neural stem cells alone. The cerebral palsy model was established by ligating the left common carotid artery followed by exposure to hypoxia. Phosphate-buffered saline, vascular endothelial growth factor + neural stem cells, and neural stem cells alone were administered into the sensorimotor cortex using the stereotaxic instrument and microsyringe. After transplantation, the radial-arm water maze test and holding test were performed. Immunohistochemistry for vascular endothelial growth factor and histology using hematoxylin-eosin were performed on cerebral cortex. Results revealed that the number of vascular endothelial growth factor-positive cells in cerebral palsy rats transplanted with vascular endothelial growth factor-transfected neural stem cells was increased, the time for finding water and the finding repetitions were reduced, the holding time was prolonged, and the degree of cell degeneration or necrosis was reduced. These findings indicate that the transplantation of vascular endothelial growth factor-transfected neural stem cells alleviates brain damage and cognitive deficits, and is neuroprotective in neonatal rats with hypoxia ischemic-mediated cerebral palsy.

  6. Endothelial dysfunction - a major mediator of diabetic vascular disease.

    PubMed

    Sena, Cristina M; Pereira, Ana M; Seiça, Raquel

    2013-12-01

    The vascular endothelium is a multifunctional organ and is critically involved in modulating vascular tone and structure. Endothelial cells produce a wide range of factors that also regulate cellular adhesion, thromboresistance, smooth muscle cell proliferation, and vessel wall inflammation. Thus, endothelial function is important for the homeostasis of the body and its dysfunction is associated with several pathophysiological conditions, including atherosclerosis, hypertension and diabetes. Patients with diabetes invariably show an impairment of endothelium-dependent vasodilation. Therefore, understanding and treating endothelial dysfunction is a major focus in the prevention of vascular complications associated with all forms of diabetes mellitus. The mechanisms of endothelial dysfunction in diabetes may point to new management strategies for the prevention of cardiovascular disease in diabetes. This review will focus on the mechanisms and therapeutics that specifically target endothelial dysfunction in the context of a diabetic setting. Mechanisms including altered glucose metabolism, impaired insulin signaling, low-grade inflammatory state, and increased reactive oxygen species generation will be discussed. The importance of developing new pharmacological approaches that upregulate endothelium-derived nitric oxide synthesis and target key vascular ROS-producing enzymes will be highlighted and new strategies that might prove clinically relevant in preventing the development and/or retarding the progression of diabetes associated vascular complications.

  7. Implications of Klotho in vascular health and disease

    PubMed Central

    Martín-Núñez, Ernesto; Donate-Correa, Javier; Muros-de-Fuentes, Mercedes; Mora-Fernández, Carmen; Navarro-González, Juan F

    2014-01-01

    Cardiovascular disease (CVD) is a prevalent condition in general population and the first cause of death overall. Klotho, a pleiotropic protein related to longevity that acts as a co-receptor of the fibroblast growth factor 23, has been proposed as a key regulator of the development of CVD. In the few clinical studies made, it has been observed a relationship between low levels of soluble Klotho and the occurrence and severity of CVD, as well as a reduction of cardiovascular risk when they are high. Also, different polymorphisms of human Klotho gene have been related to the incidence of cardiovascular events. Moreover, several experimental studies indicate that this protein acts in the maintenance of vascular homeostasis. Klotho improves endothelial dysfunction through promotion of NO production and mediates anti-inflammatory and anti-aging effects such as suppression of adhesion molecules expression, attenuation of nuclear factor-kappa B or inhibition of Wnt signaling. Furthermore, this protein is related to the attenuation of vascular calcification as well as prevention of cardiac hypertrophy. The expression of this protein in the vascular wall implies a new scenario for the treatment of vascular disorders. The purpose of this review is to provide an overview of the relationship between the Klotho protein and CVD, in addition to its role in the maintenance of functional vascular integrity. PMID:25548616

  8. Cerebral white matter lesions in patients with Crohn's disease.

    PubMed

    Chen, Merry; Lee, Grace; Kwong, Lawrence N; Lamont, Sharon; Chaves, Claudia

    2012-01-01

    To investigate the incidence, characteristics, and predisposing factors for cerebral white matter lesions in patients with Crohn's disease. We retrospectively evaluated the incidence and characteristics of cerebral T2 white matter abnormalities in 54 patients with Crohn's disease and compared to 100 age-matched controls. We also investigated potential co-morbidities known to be associated with white matter abnormalities in Crohn's patients with normal and abnormal Magnetic Resonance Imaging (MRI). Seventy-two percent of patients with Crohn's disease had T2 white matter abnormalities, as compared with 34% of the age-matched controls (P < .001). Lesion severity and size were not significantly different between the two groups; however, periventricular distribution and fulfillment of the Barkhof MRI criteria were overrepresented in Crohn's population. History of hypertension, diabetes, and migraine; gender, duration of disease and prior exposure to anti-tumor necrosis factor were not significantly different between Crohn's patients with and without white matter abnormalities; however, patients with lesions were significantly older than those without. Patients with Crohn's disease have a higher incidence of white matter T2 hyperintensities as compared with controls. Age was the only significant factor for the abnormalities within Crohn's group. White matter T2 hyperintensities are likely another extra-intestinal manifestation of Crohn's disease. Copyright © 2010 by the American Society of Neuroimaging.

  9. Pathophysiology of hypoxaemic pulmonary vascular diseases.

    PubMed

    Watanabe, S

    1987-08-01

    Chronic alveolar hypoxia whether due to living at high altitude or to lung disorders, such as chronic obstructive lung disease (COLD), leads to development of pulmonary arterial hypertension (PAH). Sustained PAH is the principal cause of right ventricular hypertrophy (RVH) and failure. The majority of high altitude residents, in spite of having moderate PAH and hypoxemia with some degree of RVH, manage to live actively and productively through acclimatization. Although the processes of acclimatization decrease the magnitude of oxygen (O2) pressure drop at each step of the O2 tension cascade, O2 pressures in the tissue capillaries and mixed venous blood are lower than those at sea level. Since the cardiac output and O2 consumption in residents at high altitude have been shown to be comparable to those of sea level residents, the importance of adaptive changes at the tissue level to facilitate diffusion and utilization of O2 must be emphasized. In patients with COLD and hypoxaemia, most of the adaptive changes that have been shown to operate in high altitude residents do not occur, or have not been observed consistently. At present, only long-term O2 therapy has been shown to improve survival and lower pulmonary artery pressure (Ppa), but the changes of the latter are generally too modest to explain the former. It may be that the improved survival is mainly achieved by correcting hypoxaemia, thereby improving tissue oxygenation, rather than lowering Ppa.

  10. Traumatic brain injury in vivo and in vitro contributes to cerebral vascular dysfunction through impaired gap junction communication between vascular smooth muscle cells.

    PubMed

    Yu, Guang-Xiang; Mueller, Martin; Hawkins, Bridget E; Mathew, Babu P; Parsley, Margaret A; Vergara, Leoncio A; Hellmich, Helen L; Prough, Donald S; Dewitt, Douglas S

    2014-04-15

    Gap junctions (GJs) contribute to cerebral vasodilation, vasoconstriction, and, perhaps, to vascular compensatory mechanisms, such as autoregulation. To explore the effects of traumatic brain injury (TBI) on vascular GJ communication, we assessed GJ coupling in A7r5 vascular smooth muscle (VSM) cells subjected to rapid stretch injury (RSI) in vitro and VSM in middle cerebral arteries (MCAs) harvested from rats subjected to fluid percussion TBI in vivo. Intercellular communication was evaluated by measuring fluorescence recovery after photobleaching (FRAP). In VSM cells in vitro, FRAP increased significantly (p<0.05 vs. sham RSI) after mild RSI, but decreased significantly (p<0.05 vs. sham RSI) after moderate or severe RSI. FRAP decreased significantly (p<0.05 vs. sham RSI) 30 min and 2 h, but increased significantly (p<0.05 vs. sham RSI) 24 h after RSI. In MCAs harvested from rats 30 min after moderate TBI in vivo, FRAP was reduced significantly (p<0.05), compared to MCAs from rats after sham TBI. In VSM cells in vitro, pretreatment with the peroxynitrite (ONOO(-)) scavenger, 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron[III], prevented RSI-induced reductions in FRAP. In isolated MCAs from rats treated with the ONOO(-) scavenger, penicillamine, GJ coupling was not impaired by fluid percussion TBI. In addition, penicillamine treatment improved vasodilatory responses to reduced intravascular pressure in MCAs harvested from rats subjected to moderate fluid percussion TBI. These results indicate that TBI reduced GJ coupling in VSM cells in vitro and in vivo through mechanisms related to generation of the potent oxidant, ONOO(-).

  11. Optical detection of brain function: simultaneous imaging of cerebral vascular response, tissue metabolism, and cellular activity in vivo.

    PubMed

    Du, Congwu; Pan, Yingtian

    2011-01-01

    It is known that a remaining challenge for functional brain imaging is to distinguish the coupling and decoupling effects among neuronal activity, cerebral metabolism, and vascular hemodynamics, which highlights the need for new tools to enable simultaneous measures of these three properties in vivo. Here, we review current neuroimaging techniques and their prospects and potential limitations for tackling this challenge. We then report a novel dual-wavelength laser speckle imaging (DW-LSI) tool developed in our labs that enables simultaneous imaging of cerebral blood flow (CBF), cerebral blood volume, and tissue hemoglobin oxygenation, which allows us to monitor neurovascular and tissue metabolic activities at high spatiotemporal resolutions over a relatively large field of view. Moreover, we report digital frequency ramping Doppler optical coherence tomography (DFR-OCT) that allows for quantitative 3D imaging of the CBF network in vivo. In parallel, we review calcium imaging techniques to track neuronal activity, including intracellular calcium approach using Rhod2 fluorescence technique that we develop to detect neuronal activity in vivo. We report a new multimodality imaging platform that combines DW-LSI, DFR-OCT, and calcium fluorescence imaging for simultaneous detection of cortical hemodynamics, cerebral metabolism, and neuronal activities of the animal brain in vivo, as well as its integration with microprobes for imaging neuronal function in deep brain regions in vivo. Promising results of in vivo animal brain functional studies suggest the potential of this multimodality approach for future awake animal and behavioral studies.

  12. The Medtronic Micro Vascular Plug™ for Vascular Embolization in Children With Congenital Heart Diseases.

    PubMed

    Sathanandam, Shyam; Justino, Henri; Waller, B Rush; Gowda, Srinath T; Radtke, Wolfgang; Qureshi, Athar M

    2017-04-01

    To describe the early multi-center, clinical experience with the Medtronic Micro Vascular Plug™ (MVP) in children with congenital heart disease (CHD) undergoing vascular embolization. The MVP is a large diameter vascular occlusion device that can be delivered through a microcatheter for embolization of abnormal blood vessels. A retrospective review of embolization procedures using the MVP in children with CHD was performed in 3-centers. Occlusion of patent ductus arteriosus using the MVP was not included. Ten children underwent attempted occlusion using the MVP. The most common indication to use the MVP was failed attempted occlusion using other embolic devices. Five, single ventricle patients (median age 3-years, median weight 14.9 kg) underwent occlusion of veno-venous collaterals following bidirectional Glenn operation. Three patients (Median age 8 years) underwent occlusion of coronary artery fistulae (CAF). Two patients (age 7 months and 1 year) underwent occlusion of large aorto-pulmonary collaterals. A 7-day-old child with a large CAF required 2 MVPs and an Amplatzer Vascular Plug (AVP-II) for complete occlusion. Occlusion of all other blood vessels was achieved using a single MVP. One MVP embolized distally in an 8-years-old child with a large CAF. There were no other procedural complications or during follow-up (median 9 months). The MVP is a new, large-diameter vascular embolization device that can be delivered through a microcatheter. It may play an important role in providing highly effective occlusion of abnormal vessels in children. © 2017, Wiley Periodicals, Inc.

  13. Vascular health late after Kawasaki disease: implications for accelerated atherosclerosis

    PubMed Central

    2014-01-01

    Kawasaki disease (KD), an acute vasculitis that primarily affects young children, is the most common acquired paediatric cardiovascular disease in developed countries. While sequelae of arterial inflammation in the acute phase of KD are well documented, its late effects on vascular health are increasingly unveiled. Late vascular dysfunction is characterized by structural alterations and functional impairment in term of arterial stiffening and endothelial dysfunction and shown to involve both coronary and systemic arteries. Further evidence suggests that continuous low grade inflammation and ongoing active remodeling of coronary arterial lesions occur late after acute illness and may play a role in structural and functional alterations of the arteries. Potential importance of genetic modulation on vascular health late after KD is implicated by associations between mannose binding lectin and inflammatory gene polymorphisms with severity of peripheral arterial stiffening and carotid intima-media thickening. The changes in cholesterol and lipoproteins levels late after KD further appear similar to those proposed to be atherogenic. While data on adverse vascular health are less controversial in patients with persistent or regressed coronary arterial aneurysms, data appear conflicting in individuals with no coronary arterial involvements or only transient coronary ectasia. Notwithstanding, concerns have been raised with regard to predisposition of KD in childhood to accelerated atherosclerosis in adulthood. Until further evidence-based data are available, however, it remains important to assess and monitor cardiovascular risk factors and to promote cardiovascular health in children with a history of KD in the long term. PMID:25550701

  14. Extracellular vesicles as mediators of vascular inflammation in kidney disease

    PubMed Central

    Helmke, Alexandra; von Vietinghoff, Sibylle

    2016-01-01

    Vascular inflammation is a common cause of renal impairment and a major cause of morbidity and mortality of patients with kidney disease. Current studies consistently show an increase of extracellular vesicles (EVs) in acute vasculitis and in patients with atherosclerosis. Recent research has elucidated mechanisms that mediate vascular wall leukocyte accumulation and differentiation. This review addresses the role of EVs in this process. Part one of this review addresses functional roles of EVs in renal vasculitis. Most published data address anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis and indicate that the number of EVs, mostly of platelet origin, is increased in active disease. EVs generated from neutrophils by activation by ANCA can contribute to vessel damage. While EVs are also elevated in other types of autoimmune vasculitis with renal involvement such as systemic lupus erythematodes, functional consequences beyond intravascular thrombosis remain to be established. In typical hemolytic uremic syndrome secondary to infection with shiga toxin producing Escherichia coli, EV numbers are elevated and contribute to toxin distribution into the vascular wall. Part two addresses mechanisms how EVs modulate vascular inflammation in atherosclerosis, a process that is aggravated in uremia. Elevated numbers of circulating endothelial EVs were associated with atherosclerotic complications in a number of studies in patients with and without kidney disease. Uremic endothelial EVs are defective in induction of vascular relaxation. Neutrophil adhesion and transmigration and intravascular thrombus formation are critically modulated by EVs, a process that is amenable to therapeutic interventions. EVs can enhance monocyte adhesion to the endothelium and modulate macrophage differentiation and cytokine production with major influence on the local inflammatory milieu in the plaque. They significantly influence lipid phagocytosis and antigen presentation by

  15. Risk factors for atherosclerotic vascular disease.

    PubMed

    von Eckardstein, A

    2005-01-01

    Several controlled interventional trials have shown the benefit of anti-hypertensive and hypolipidaemic drugs for the prevention of coronary heart disease (CHD). International guidelines for the prevention of CHD agree in their recommendations for tertiary prevention and recommend lowering the blood pressure to below 140 mm/90 mm Hg and low density lipoprotein (LDL)-cholesterol to below 2.6 mmol/l in patients with manifest CHD. Novel recommendations for secondary prevention are focused on the treatment of the pre-symptomatic high-risk patient with an estimated CHD morbidity risk of higher than 20% per 10 years or an estimated CHD mortality risk of higher than 5% per 10 years. For the calculation of this risk, the physician must record the following risk factors: sex, age, family history of premature myocardial infarction, smoking, diabetes, blood pressure, total cholesterol, LDL-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglyceride. This information allows the absolute risk of myocardial infarction to be computed by using scores or algorithms which have been deduced from results of epidemiological studies. To improve risk prediction and to identify new targets for intervention, novel risk factors are sought. High plasma levels of C-reactive protein has been shown to improve the prognostic value of global risk estimates obtained by the combination of conventional risk factors and may influence treatment decisions in patients with intermediate global cardiovascular risk (CHD morbidity risk of 10%-20% per 10 years or CHD mortality risk of 2%-5% per 10 years).

  16. Potential of optical microangiography to monitor cerebral blood perfusion and vascular plasticity following traumatic brain injury in mice in vivo

    NASA Astrophysics Data System (ADS)

    Jia, Yali; Alkayed, Nabil; Wang, Ruikang K.

    2009-07-01

    Optical microanglography (OMAG) is a recently developed imaging modality capable of volumetric imaging of dynamic blood perfusion, down to capillary level resolution, with an imaging depth up to 2.00 mm beneath the tissue surface. We report the use of OMAG to monitor the cerebral blood flow (CBF) over the cortex of mouse brain upon traumatic brain injury (TBI), with the cranium left intact, for a period of two weeks on the same animal. We show the ability of OMAG to repeatedly image 3-D cerebral vasculatures during pre- and post-traumatic phases, and to visualize the changes of regulated CBF and the vascular plasticity after TBI. The results indicate the potential of OMAG to explore the mechanism involved in the rehabilitation of TBI.

  17. Crystal Structure of CCM3, a Cerebral Cavernous Malformation Protein Critical for Vascular Integrity

    SciTech Connect

    Li, X.; Zhang, R; Zhang, H; He, Y; Ji, W; Min, W; Boggon, T

    2010-01-01

    CCM3 mutations are associated with cerebral cavernous malformation (CCM), a disease affecting 0.1-0.5% of the human population. CCM3 (PDCD10, TFAR15) is thought to form a CCM complex with CCM1 and CCM2; however, the molecular basis for these interactions is not known. We have determined the 2.5 {angstrom} crystal structure of CCM3. This structure shows an all {alpha}-helical protein containing two domains, an N-terminal dimerization domain with a fold not previously observed, and a C-terminal focal adhesion targeting (FAT)-homology domain. We show that CCM3 binds CCM2 via this FAT-homology domain and that mutation of a highly conserved FAK-like hydrophobic pocket (HP1) abrogates CCM3-CCM2 interaction. This CCM3 FAT-homology domain also interacts with paxillin LD motifs using the same surface, and partial CCM3 co-localization with paxillin in cells is lost on HP1 mutation. Disease-related CCM3 truncations affect the FAT-homology domain suggesting a role for the FAT-homology domain in the etiology of CCM.

  18. Crystal structure of CCM3, a cerebral cavernous malformation protein critical for vascular integrity.

    PubMed

    Li, Xiaofeng; Zhang, Rong; Zhang, Haifeng; He, Yun; Ji, Weidong; Min, Wang; Boggon, Titus J

    2010-07-30

    CCM3 mutations are associated with cerebral cavernous malformation (CCM), a disease affecting 0.1-0.5% of the human population. CCM3 (PDCD10, TFAR15) is thought to form a CCM complex with CCM1 and CCM2; however, the molecular basis for these interactions is not known. We have determined the 2.5 A crystal structure of CCM3. This structure shows an all alpha-helical protein containing two domains, an N-terminal dimerization domain with a fold not previously observed, and a C-terminal focal adhesion targeting (FAT)-homology domain. We show that CCM3 binds CCM2 via this FAT-homology domain and that mutation of a highly conserved FAK-like hydrophobic pocket (HP1) abrogates CCM3-CCM2 interaction. This CCM3 FAT-homology domain also interacts with paxillin LD motifs using the same surface, and partial CCM3 co-localization with paxillin in cells is lost on HP1 mutation. Disease-related CCM3 truncations affect the FAT-homology domain suggesting a role for the FAT-homology domain in the etiology of CCM.

  19. Associations between cerebral small-vessel disease and Alzheimer disease pathology as measured by cerebrospinal fluid biomarkers.

    PubMed

    Kester, Maartje I; Goos, Jeroen D C; Teunissen, Charlotte E; Benedictus, Marije R; Bouwman, Femke H; Wattjes, Mike P; Barkhof, Frederik; Scheltens, Philip; van der Flier, Wiesje M

    2014-07-01

    It remains unclear if and how associations between cerebral small-vessel disease and Alzheimer disease (AD) pathology lead to cognitive decline and dementia. To determine associations between small-vessel disease and AD pathology. Cross-sectional study from January 2002 to December 2012 using the memory clinic-based Amsterdam Dementia Cohort. The study included 914 consecutive patients with available cerebrospinal fluid (CSF) and magnetic resonance imaging; 547 were patients diagnosed as having AD (54% female, mean [SD], 67 [8]; Mini-Mental State Examination score, mean [SD], 21 [5]), 30 were patients diagnosed as having vascular dementia (37% female, mean [SD], 76 [9]; Mini-Mental State Examination score, mean [SD], 24 [4]), and 337 were control participants with subjective memory complaints (42% female, mean [SD], 59 [59]; Mini-Mental State Examination score, mean [SD], 28 [2]). Linear regressions were performed with CSF biomarkers (log transformed) as dependent variables and magnetic resonance imaging measures (dichotomized) as independent, adjusted for sex, age, mediotemporal lobe atrophy, and diagnosis. An interaction term for diagnosis by magnetic resonance imaging measures was used for estimates per diagnostic group. We examined the associations of magnetic resonance imaging white matter hyperintensities (WMH), lacunes, microbleeds with CSF β-amyloid 42 (Aβ42), total tau, and tau phosphorylated at threonine 181 (P-tau181) as well as for a subset of apolipoprotein E (APOE) ε4 carriers and noncarriers. Microbleed presence was associated with lower CSF Aβ42 in AD and vascular dementia (standardized beta = -0.09, P = .003; standardized beta = -0.30, P = .01), and higher CSF tau in controls (standardized beta = 0.10, P = .03). There were no effects for P-tau181. The presence of WMH was associated with lower Aβ42 in control participants and patients with vascular dementia (standardized beta = -0.18, P = .002; standardized beta

  20. Gorham's disease in humerus treated with autogenous vascularized fibular graft

    PubMed Central

    Kim, Jeung Woo; Kang, Hong Je; Kim, Dong Chul; Shin, Chang Hyun

    2017-01-01

    Gorham's disease is a rare disorder of the bone characterized by progressive massive osteolysis. The pathophysiology is unknown, and diagnosis is often difficult. Most cases are often recognized retrospectively. There is no standardized treatment and management for Gorham's disease. We report a case of an 18-year-old male presenting with a pathologic fracture in the humerus shaft diagnosed with Gorham's disease. Patient was treated with autogenous vascularized fibular graft with wide excision and a 10 years followup after first surgery. PMID:28400670

  1. Novel Applications of Radionuclide Imaging in Peripheral Vascular Disease

    PubMed Central

    Stacy, Mitchel R.; Sinusas, Albert J.

    2015-01-01

    Peripheral vascular disease (PVD) is a progressive atherosclerotic disease that leads to stenosis or occlusion of blood vessels supplying the lower extremities. Current diagnostic imaging techniques commonly focus on evaluation of anatomy or blood flow at the macrovascular level and do not permit assessment of the underlying pathophysiology associated with disease progression or treatment response. Molecular imaging with radionuclide-based approaches, such as PET and SPECT, can offer novel insight into PVD by providing non-invasive assessment of biological processes such as angiogenesis and atherosclerosis. This review discusses emerging radionuclide-based imaging approaches that have potential clinical applications in the evaluation of PVD progression and treatment. PMID:26590787

  2. Novel Applications of Radionuclide Imaging in Peripheral Vascular Disease.

    PubMed

    Stacy, Mitchel R; Sinusas, Albert J

    2016-02-01

    Peripheral vascular disease (PVD) is a progressive atherosclerotic disease that leads to stenosis or occlusion of blood vessels supplying the lower extremities. Current diagnostic imaging techniques commonly focus on evaluation of anatomy or blood flow at the macrovascular level and do not permit assessment of the underlying pathophysiology associated with disease progression or treatment response. Molecular imaging with radionuclide-based approaches can offer novel insight into PVD by providing noninvasive assessment of biological processes such as angiogenesis and atherosclerosis. This article discusses emerging radionuclide-based imaging approaches that have potential clinical applications in the evaluation of PVD progression and treatment.

  3. Vascular calcification in chronic kidney disease: a clinical review.

    PubMed

    Eddington, Helen; Sinha, Smeeta; Kalra, Philip A

    2009-03-01

    Vascular calcification, which is associated with arterial stiffness, is now known to be an important predictor of cardiovascular and all-cause mortality in patients with renal disease. This calcification starts developing in the early stages of chronic kidney disease (CKD) and is present in over 50% of patients at the time of dialysis commencement. Once calcification is present it continues to progress, though some medications have been shown to slow this progression. Vascular calcification and bone abnormalities are now both encompassed by the term of CKD-mineral bone disorder and are thought to be part of the same disease process in CKD. Vascular calcification and arterial stiffness have been extensively researched in the renal population and many factors are known to be associated with their presence and progression. This calcification is an important factor to be considered in the management of the renal patient but there are different methods available for its measurement. These details will be discussed further in this review along with evidence available for management of this important complication of renal disease.

  4. Vascular-derived reactive oxygen species for homeostasis and diseases.

    PubMed

    Satoh, Kimio; Berk, Bradford C; Shimokawa, Hiroaki

    2011-08-01

    Numerous basic and clinical studies have clearly identified that reactive oxygen species (ROS, i.e., H(2)O(2), O(2)(-), and ()OH) has a major role in the development of cardiovascular diseases. However, we still have no strong therapeutic strategy for clinical benefits of antioxidant administration. One potential reason for those could be a crucial role of ROS for intracellular signaling pathways that is important for vascular functions in a very low concentration. ROS contributes to the physiology and pathology of vasculature, but precise molecular regulations remain elusive. The mechanism how excessive ROS (oxidative stress) deteriorate vascular function and promote vascular diseases has not been clearly elucidated. Cyclophilin A (CyPA) has been studied as a multifunctional protein that is upregulated in a variety of inflammatory conditions, such as rheumatoid arthritis, autoimmune disease, and cancer. CyPA has been classified as an immunophilins and has a variety of intracellular functions including intracellular signaling, protein trafficking, and the regulating other proteins. Besides intracellular functions, we revealed that CyPA is a secreted molecule that has a pathological role in the cardiovascular system. CyPA has emerged as a potential biomarker and mediator of cardiovascular disease. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Cerebral blood volume in Alzheimer's disease and correlation with tissue structural integrity.

    PubMed

    Uh, Jinsoo; Lewis-Amezcua, Kelly; Martin-Cook, Kristin; Cheng, Yamei; Weiner, Myron; Diaz-Arrastia, Ramon; Devous, Michael; Shen, Dinggang; Lu, Hanzhang

    2010-12-01

    A vascular component is increasingly recognized as important in Alzheimer's disease (AD). We measured cerebral blood volume (CBV) in patients with probable AD or Mild Cognitive Impairment (MCI) and in elderly non-demented subjects using a recently developed Vascular-Space-Occupancy (VASO) MRI technique. While both gray and white matters were examined, significant CBV deficit regions were primarily located in white matter, specifically in frontal and parietal lobes, in which CBV was reduced by 20% in the AD/MCI group. The regions with CBV deficit also showed reduced tissue structural integrity as indicated by increased apparent diffusion coefficients, whereas in regions without CBV deficits no such correlation was found. Subjects with lower CBV tended to have more white matter lesions in FLAIR MRI images and showed slower psychomotor speed. These data suggest that the vascular contribution in AD is primarily localized to frontal/parietal white matter and is associated with brain tissue integrity. Copyright © 2008 Elsevier Inc. All rights reserved.

  6. Hyponatremia in acute brain disease: the cerebral salt wasting syndrome.

    PubMed

    Betjes, Michiel G.H.

    2002-02-01

    Hyponatremia in acute brain disease is a common occurrence, especially after an aneurysmal subarachnoid hemorrhage. Originally, excessive natriuresis, called cerebral salt wasting, and later the syndrome of inappropriate antidiuretic hormone secretion (SIADH), were considered to be the causes of hyponatremia. In recent years, it has become clear that most of these patients are volume-depleted and have a negative sodium balance, consistent with the original description of cerebral salt wasting. Elevated plasma concentrations of atrial or brain natriuretic peptide have been identified as the putative natriuretic factor. Hyponatremia and volume depletion may aggravate neurological symptoms, and timely treatment with adequate replacement of water and NaCl is essential. The use of fludrocortisone to increase sodium reabsorption by the renal tubules may be an alternative approach.

  7. Motor neuron disease: biomarker development for an expanding cerebral syndrome.

    PubMed

    Turner, Martin R

    2016-12-01

    Descriptions of motor neuron disease (MND) documented more than a century ago remain instantly recognisable to the physician. The muscle weakness, typically with signs of upper and lower motor neuron dysfunction, is uniquely relentless. Over the last 30 years, a wider cerebral pathology has emerged, despite the lack of overt cognitive impairment in the majority of patients. From the initial linkage of a small number of cases to mutations in SOD1, diverse cellular pathways have been implicated in pathogenesis. An increasingly complex clinical heterogeneity has emerged around a significant variability in survival. Defining a cellular signature of aggregated TDP-43 common to nearly all MND and a large proportion of frontotemporal dementia (FTD), has placed MND alongside more traditional cerebral neurodegeneration. With new genetic causes, most notably a hexanucleotide expansion in C9orf72 associated with both MND and FTD, the development of biomarkers against which to test therapeutic candidates is a priority.

  8. Silent Cerebral Small Vessel Disease in Restless Legs Syndrome.

    PubMed

    Ferri, Raffaele; Cosentino, Filomena I I; Moussouttas, Michael; Lanuzza, Bartolo; Aricò, Debora; Bagai, Kanika; Wang, Lily; McLaughlin, BethAnn; Walters, Arthur S

    2016-07-01

    Growing literature suggests that patients with restless legs syndrome (RLS) may be at increased risk for hypertension, heart disease, and stroke. Cerebral small vessel disease (SVD) is a known risk factor for clinical stroke. This study evaluated silent cerebral SVD by MRI in patients with RLS, in the absence of a history of previous clinical stroke or known stroke risk factors and taking into account disease duration. Fifty-three patients with RLS < 10 y were prospectively recruited along with 44 with RLS > 10 y and 74 normal controls. A magnetic resonance imaging study was obtained from all subjects and scans were analyzed for area and volume of SVD. There was a significant increase in SVD area in the entire group of RLS patients compared to controls (P = 0.036); this was almost entirely driven by the group with RLS > 10 y. SVD area and volume were significantly increased in patients with RLS > 10 y with respect to both controls (P < 0.0001 and P < 0.0014, respectively) and RLS < 10 y (P < 0.00022 and P < 0.003, respectively). Age, duration of RLS, and the interaction of age and duration of RLS were independent predictors of SVD disease. Duration of RLS was an independent predictor of the burden of cerebral SVD (area P < 0.00012 and volume P < 0.0025), whereas sex and insomnia were not. RLS duration should be taken into account when analyzing the association between RLS and cerebrovascular disease; our data support the hypothesis that a long-lasting RLS and its accompanying periodic limb movements in sleep are a risk factor for silent SVD and perhaps for the development of clinical stroke. © 2016 Associated Professional Sleep Societies, LLC.

  9. DETERMINANTS OF RESTING CEREBRAL BLOOD FLOW IN SICKLE CELL DISEASE

    PubMed Central

    Bush, Adam M; Borzage, Matthew T; Choi, Soyoung; Václavů, Lena; Tamrazi, Benita; Nederveen, Aart J; Coates, Thomas D; Wood, John C

    2016-01-01

    Stroke is common in children with sickle cell disease and results from an imbalance in oxygen supply and demand. Cerebral blood flow (CBF) is increased in patients with sickle cell disease to compensate for their anemia, but adequacy of their oxygen delivery has not been systematically demonstrated. This study examined the physiological determinants of CBF in 37 patients with sickle cell disease, 38 ethnicity matched control subjects and 16 patients with anemia of non-sickle origin. Cerebral blood flow was measured using phase contrast MRI of the carotid and vertebral arteries. CBF increased inversely to oxygen content (r2 = 0.69, p < 0.0001). Brain oxygen delivery, the product of CBF and oxygen content, was normal in all groups. Brain composition, specifically the relative amounts of grey and white matter, was the next strongest CBF predictor, presumably by influencing cerebral metabolic rate. Grey matter/white matter ratio and CBF declined monotonically until the age of 25 in all subjects, consistent with known maturational changes in brain composition. Further CBF reductions were observed with age in subjects older than 35 years of age, likely reflecting microvascular aging. On multivariate regression, CBF was independent of disease state, hemoglobin S, hemoglobin F, reticulocyte count and cell free hemoglobin, suggesting that it is regulated similarly in patients and control subjects. In conclusion, sickle cell disease patients had sufficient oxygen delivery at rest, but accomplish this only by marked increases in their resting CBF, potentially limiting their ability to further augment flow in response to stress. PMID:27263497

  10. Central Pulsatile Pressure and Flow Relationship in the Time and Frequency Domain to Characterise Hydraulic Input to the Brain and Cerebral Vascular Impedance.

    PubMed

    Kim, Mi Ok; O'Rourke, Michael F; Adji, Audrey; Avolio, Alberto P

    2016-01-01

    In the time domain, pulsatile flow and pressure can be characterised as the ratio of the late systolic boost of flow or pressure to the pulse amplitude so as to estimate the hydraulic input to the brain. While vascular impedance has been widely used to represent the load presented to the heart by the systemic circulation, it has not been applied to the cerebral circulation.We set out to study the relationship between the pressure and the flow augmentation index (AIx) in the time domain and to determine cerebral vascular impedance using aortic blood pressure and cerebral blood flow waveforms in the frequency domain. Twenty-four young subjects (aged 21-39 years) were recruited; aortic pressure was derived using SphygmoCor from radial pressure. Flow waveforms were recorded from the middle cerebral artery. In three subjects, we performed the Valsalva manoeuvre to investigate their response to physiological intervention. There was a linear relationship between flow and pressure AIx, and cerebral impedance values were similar to those estimated for low resistance vascular beds. Substantial change in pressure and flow wave contour was observed during the Valsalva manoeuvre; however, the relationship in both the time and the frequency domains were unchanged. This confirms that aortic pressure and cerebral flow waveform can be used to study cerebral impedance.

  11. [Hyaline-vascular Multicentric Castleman's Disease in an immunocompetent patient].

    PubMed

    Zapata-Bonilla, Sergio Armando; López Vargas, Roberto; Scherling-Ocampo, Aldo Alfonso; Morales Leyte, Ana Lilia; García Ilizaliturri, Liliana

    2015-01-01

    A previously healthy, immunocompetent 67-year-old female presented with a one-month history of general symptoms, weight loss, night fevers, and bilateral lower extremity edema. On admission she had severe anemia, acute kidney injury, and multiple lymphadenopathies. An excisional biopsy of one of the axillary lymphadenopathies confirmed hyaline-vascular Castleman's disease. This rare disease is a polyclonal lymphoproliferative disorder that affects the normal lymph node architecture. According to its location it can be divided in unicentric (localized) or multicentric disease; it can be further divided according to histopathology in hyaline-vascular or plasmatic cells variety. Clinical presentation relates more to histopathological variety than to centricity. Human herpes virus 8 is ubiquitous in this disease and, along with interleukin 6, plays an important role in pathogenesis and symptoms presentation. Surgery is the go-to treatment of localized disease, while systemic chemotherapy is the option in multicentric disease. Communication between the clinical and anatomopathological teams is crucial; lag in diagnosis can lead to futile investigations in search of other diseases and delay in treatment.

  12. Cerebral abscess after neuro-vascular embolization: Own experience and review of the literature.

    PubMed

    Cossu, G; Daniel, R T; Messerer, M

    2017-03-01

    Cerebral abscesses are a rare complication after therapeutic neuro-endovascular procedures. The aim of this article is to report a case of cerebral abscess after the endovascular embolization of a cerebral aneurysm and to discuss and review all the cases of cerebral abscess secondary to neurovascular embolization described in the literature up to now. A 40-year-old female patient was treated using an endovascular embolization for a ruptured aneurysm of the basilar artery tip. After 2 months she presented with a cerebellar abscess. Antibiotic therapy was started, and a surgical drainage of the collection was performed, with a favorable postoperative outcome. Twelve other cases were reported in the literature, in five cases secondary to the treatment of a cerebral aneurysm, in six cases secondary to a cerebral arterio-venous malformation (AVM) and in one case secondary to a dural arterio-venous fistula (DAVF). The pathophysiology and risk factors of cerebral abscess formation are discussed in detail. The risk of cerebral abscesses after neuro-endovascular embolization is not negligible, and a growing number of patients affected by this complication may be expected in the near future because of the spreading of neuro-endovascular techniques. The role of prophylactic antibiotic therapy in specific subgroups of patients is still debated.

  13. Alzheimer's Disease with Vascular Component: A Distinct Clinical Entity?

    PubMed Central

    Olazarán, Javier; Navarro, Eloísa; Rojo, José Manuel

    2012-01-01

    Background Longitudinal reports on the clinical features of patients with Alzheimer's disease (AD) and concomitant cerebrovascular disease are scarce. Methods We elaborated a working definition of AD with vascular component (ADVC), and this definition was retrospectively investigated in a cohort of patients with cognitive deterioration who were prescribed a cholinesterase inhibitor during usual practice. Results A total of 137 patients with probable AD and 66 patients with ADVC were studied during a mean follow-up period of 2.8 years. Univariate analyses demonstrated worse functional evolution and anticipation of psychotic symptoms and agitation in the ADVC group. Conclusions The present results are consistent with an additive model of predominantly frontal-subcortical vascular damage in AD. PMID:23139685

  14. Vascular disease and vascular risk factors in relation to motor features and cognition in early Parkinson's disease.

    PubMed

    Malek, Naveed; Lawton, Michael A; Swallow, Diane M A; Grosset, Katherine A; Marrinan, Sarah L; Bajaj, Nin; Barker, Roger A; Burn, David J; Hardy, John; Morris, Huw R; Williams, Nigel M; Wood, Nicholas; Ben-Shlomo, Yoav; Grosset, Donald G

    2016-10-01

    The purpose of this study was to examine the relationship between vascular disease (and vascular risk factors), cognition and motor phenotype in Parkinson's disease (PD). Recently diagnosed PD cases were enrolled in a multicenter prospective observational longitudinal cohort study. Montreal cognitive assessment (normal >23, mild cognitive impairment 22 to 23 or lower but without functional impairment, and dementia 21 or less with functional impairment) and Movement Disorder Society Unified PD Rating Scale part 3 (UPDRS 3) scores were analyzed in relation to a history of vascular events and risk factors. In 1759 PD cases, mean age 67.5 (standard deviation 9.3) years, mean disease duration 1.3 (standard deviation 0.9) years, 65.2% were men, 4.7% had a history of prior stroke or transient ischemic attack, and 12.5% had cardiac disease (angina, myocardial infarction, heart failure). In cases without a history of vascular disease, hypertension was recorded in 30.4%, high cholesterol 27.3%, obesity 20.7%, diabetes 7.2%, and cigarette smoking in 4.6%. Patients with prior stroke or transient ischemic attack were more likely to have cognitive impairment (42% vs 25%) and postural instability gait difficulty (53.5% vs 39.5%), but these findings were not significant after adjustment for age, sex, and disease duration (P = .075). The presence of more than 2 vascular risks was associated with worse UPDRS 3 motor scores (beta coefficient 4.05, 95% confidence interval 1.48, 6.61, p = .002) and with cognitive impairment (ordinal odds ratio 2.24, 95% confidence interval 1.34, 3.74, p = .002). In 842 patients (47.8%) with structural brain imaging, white matter leukoaraiosis, but not lacunar or territorial infarction, was associated with impaired cognition (p = .006) and postural instability gait difficulty (p = .010). Vascular comorbidity is significantly associated with cognitive and gait impairment in patients with early PD, which may have prognostic and treatment implications.

  15. Oxidative stress and microRNAs in vascular diseases.

    PubMed

    Magenta, Alessandra; Greco, Simona; Gaetano, Carlo; Martelli, Fabio

    2013-08-22

    Oxidative stress has been demonstrated to play a causal role in different vascular diseases, such as hypertension, diabetic vasculopathy, hypercholesterolemia and atherosclerosis. Indeed, increased reactive oxygen species (ROS) production is known to impair endothelial and vascular smooth muscle cell functions, contributing to the development of cardiovascular diseases. MicroRNAs (miRNAs) are non-coding RNA molecules that modulate the stability and/or the translational efficiency of target messenger RNAs. They have been shown to be modulated in most biological processes, including in cellular responses to redox imbalance. In particular, miR-200 family members play a crucial role in oxidative-stress dependent endothelial dysfunction, as well as in cardiovascular complications of diabetes and obesity. In addition, different miRNAs, such as miR-210, have been demonstrated to play a key role in mitochondrial metabolism, therefore modulating ROS production and sensitivity. In this review, we will discuss miRNAs modulated by ROS or involved in ROS production, and implicated in vascular diseases in which redox imbalance has a pathogenetic role.

  16. IR imaging of blood circulation of patients with vascular disease

    NASA Astrophysics Data System (ADS)

    Wang, Hsin; Wade, Dwight R., Jr.; Kam, Jack

    2004-04-01

    We conducted a preliminary IR imaging study of blood circulation in patients with peripheral vascular diseases. Abnormal blood flow is common in older adults, especially those with elevated blood lipids, diabetes, hypertension, and a history of smoking. All of these conditions have a high prevalence in our population, often with more than one condition in the same individual. The differences in blood flow is revealed by temperature differences in areas of the extremities as well as other regions of the body. However, what is needed is an imaging technique that is relatively inexpensive and can reveal the blood flow in real time. The IR imaging can show detailed venous system and small tempearture changes associated with blood flow. Six patients with vascular diseases were tested in a clinic set up. Their legs and feet were imaged. We observed large temperature differences (cooling of more than 10° C) at the foot, especially toes. More valuable information were obtained from the temperature distribution maps. IR thermography is potentially a very valuable tool for medical application, especially for vascular diseases.

  17. Putative mechanisms behind effects of spinal cord stimulation on vascular diseases: a review of experimental studies

    PubMed Central

    Wu, Mingyuan; Linderoth, Bengt; Foreman, Robert D.

    2008-01-01

    Spinal cord stimulation (SCS) is a widely used clinical technique to treat ischemic pain in peripheral, cardiac and cerebral vascular diseases. The use of this treatment advanced rapidly during the late 80's and 90's, particularly in Europe. Although the clinical benefits of SCS are clear and the success rate remains high, the mechanisms are not yet completely understood. SCS at lumbar spinal segments (L2-L3) produces vasodilation in the lower limbs and feet which is mediated by antidromic activation of sensory fibers and decreased sympathetic outflow. SCS at thoracic spinal segments (T1-T2) induces several benefits including pain relief, reduction in both frequency and severity of angina attacks, and reduced short-acting nitrate intake. The benefits to the heart are not likely due to an increase, or redistribution of local blood flow, rather, they are associated with SCS-induced myocardial protection and normalization of the intrinsic cardiac nervous system. At somewhat lower cervical levels (C3-C6), SCS induces increased blood flow in the upper extremities. SCS at the upper cervical spinal segments (C1-C2) increased cerebral blood flow, which is associated with a decrease in sympathetic activity, an increase in vasomotor center activity and a release of neurohumoral factors. This review will summarize the basic science studies that have contributed to our understanding about mechanisms through which SCS produces beneficial effects when used in the treatment of vascular diseases. Furthermore, this review will particularly focus on the antidromic mechanisms of SCS-induced vasodilation in the lower limbs and feet. PMID:18083639

  18. Cerebral blood flow in sickle cell cerebrovascular disease

    SciTech Connect

    Huttenlocher, P.R.; Moohr, J.W.; Johns, L.; Brown, F.D.

    1984-05-01

    Cerebral blood flow (CBF) has been studied by the xenon-133 (/sup 133/Xe) inhalation method in 16 children with suspected sickle cell cerebrovascular disease. Abnormalities consisting of decreases in total, hemispheral, or regional CBF were found in 17 of 26 studies. Eleven studies performed immediately after stroke, transient ischemic attack, or depression of state of alertness showed abnormalities. In addition to confirming regional cerebrovascular insufficiency in children with stroke due to major cerebral artery occlusion, the method detected diffuse decrease in CBF in children with stupor, coma, and seizures who had normal angiographic findings. In contrast, six of seven studies obtained after exchange transfusion or during maintenance on hypertransfusion therapy showed normal findings. The difference between results in patients with acute neurologic disturbances and those receiving transfusion therapy was statistically significant (P less than .005). The data indicate that the /sup 133/Xe method reliably demonstrates cerebrovascular impairment in sickle cell disease. They also suggest that CBF changes in patients with sickle cell disease can be reversed by exchange transfusion and by hypertransfusion therapy. The /sup 133/Xe CBF method may be useful for following up children with sickle cell disease who are at high risk for recurrent stroke.

  19. Association between Bacterial Infection and Peripheral Vascular Disease: A Review

    PubMed Central

    Budzyński, Jacek; Wiśniewska, Joanna; Ciecierski, Marek; Kędzia, Anna

    2015-01-01

    There are an increasing number of data showing a clinically important association between bacterial infection and peripheral artery disease (PAD). Bacteria suspected of being involved in PAD pathogenesis are: periodontal bacteria, gut microbiota, Helicobacter pylori, and Chlamydia pneumoniae. Infectious agents may be involved in the pathogenesis of atherosclerosis via activation of a systemic or local host immunological response to contamination of extravascular tissues or the vascular wall, respectively. A systemic immunological reaction may damage vascular walls in the course of autoimmunological cross-reactions between anti-pathogen antibodies and host vascular antigens (immunological mimicry), pathogen burden mechanisms (nonspecific activation of inflammatory processes in the vascular wall), and neuroendocrine-immune cross-talk. Besides activating the inflammatory pathway, bacterial infection may trigger PAD progression or exacerbation by enhancement of platelet reactivity, by a stimulatory effect on von Willebrand factor binding, factor VIII, fibrinogen, P-selectin activation, disturbances in plasma lipids, increase in oxidative stress, and resistance to insulin. Local inflammatory host reaction and induction of atherosclerotic plaque progression and/or instability result mainly from atherosclerotic plaque colonization by microorganisms. Despite these premises, the role of bacterial infection in PAD pathogenesis should still be recognized as controversial, and randomized, controlled trials are required to evaluate the outcome of periodontal or gut bacteria modification (through diet, prebiotics, and probiotics) or eradication (using antibiotics) in hard and surrogate cardiovascular endpoints. PMID:26900306

  20. ABSORB: Postmarketing Surveillance Registry to Monitor the Everolimus-eluting Bioresorbable Vascular Scaffold in Patients With Coronary Artery Disease

    ClinicalTrials.gov

    2016-12-08

    Cardiovascular Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Coronary Restenosis; Heart Diseases; Coronary Stenosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

  1. Rac-1 as a new therapeutic target in cerebro- and cardio-vascular diseases.

    PubMed

    Carrizzo, Albino; Forte, Maurizio; Lembo, Maria; Formisano, Luigi; Puca, Annibale A; Vecchione, Carmine

    2014-01-01

    Growing evidence indicates that overproduction of reactive oxygen species (ROS) plays a prominent role in the development of cardio- and cerebro-vascular diseases. Among the mechanisms identified to produce oxidative stress in the vascular wall, those mediated by membrane-bound NAD(P)H oxidases represent a major one. NAD(P)H oxidases are a family of enzymes that generate ROS both in phagocytic and non-phagocytic cell types. Vascular NAD(P)H oxidase contains the membrane-bound subunits Nox1, Nox2 (gp91phox), Nox4 and p22phox, the catalytic site of the oxidase, and the cytosolic components p47phox and p67phox. Rac1 (Ras-related C3 botulinum toxin substrate1) is a small GTPase essential for the assembly and activation of NADPH oxidase. Several molecular and cellular studies have reported the involvement of Rac1 in different cardiovascular pathologies, such as vascular smooth muscle proliferation, cardiomyocyte hypertrophy, endothelial cell shape change, atherosclerosis and endothelial dysfunction in hypertension. In addition, increased activation of NADPH oxidase by Rac1 has been reported in animals and humans after myocardial infarction and heart failure. The Rac1/NADPH pathway has also been found involved in different pathologies of the cerebral district, such as ischemic stroke, cognitive impairment, subaracnoid hemorrhage and neuronal oxidative damage typical of several neurodegenerative disorders. In addition, thrombotic events are an important step in the onset of cardio- and cerebrovascular diseases. Rac1 has been found involved also in platelet activation, inducing actin polymerization and lamellipodia formation, which are necessary steps for platelet aggregation. Taken together, the evidence candidates Rac1 as a new pharmacological target of cardiovascular and cerebrovascular diseases. Although the involvement of Rac1 in the beneficial pleiotropic effects of drugs such as statins is well known, and the onset of numerous side effects has raised concern for the

  2. Current Treatment Strategies: Collagen Vascular Diseases in Children

    PubMed Central

    Palit, Aparna; Inamadar, Arun C

    2012-01-01

    Of the various collagen vascular diseases seen in pediatric age group, discoid lupus erythematosus, systemic lupus erythematosus, neonatal lupus erythematosus, juvenile dermatomyositis and childhood scleroderma are common and of practical importance to clinicians. Various treatment modalities of these conditions have been discussed at length. Of these, some are conventional and routine,while others are used in challenging situations of these diseases. Autologous stem cell transplant, biological therapies, intravenous immunoglobulin and narrow band ultraviolet B are among the latest therapeutic options for these difficult-to-treat conditions in children. PMID:23248363

  3. Impact of Indoxyl Sulfate on Progenitor Cell-Related Neovascularization of Peripheral Arterial Disease and Post-Angioplasty Thrombosis of Dialysis Vascular Access

    PubMed Central

    Wu, Chih-Cheng; Hung, Szu-Chun; Kuo, Ko-Lin; Tarng, Der-Cherng

    2017-01-01

    Patients with chronic kidney disease (CKD) have an increased risk of vascular disease, which is associated with considerable health care costs. Vascular disease in CKD differs clinically and pathobiologically from that in patients with normal renal function. Besides the traditional risk factors, retention of uremic toxins contributes to the pathogenesis of vascular disease in patients with CKD. Indoxyl sulfate is a protein-bound uremic toxin and is inefficiently removed by conventional dialysis. Accumulating evidence suggests that indoxyl sulfate is a vascular toxin involved in atherosclerosis, arteriosclerosis, vascular calcification and vascular repair. Clinically, indoxyl sulfate is associated with total and cardiovascular mortality in patients with CKD. Recent studies have indicated that in addition to coronary and cerebral arteries, indoxyl sulfate plays a role in peripheral artery disease (PAD) and dialysis graft thrombosis. Emerging evidence suggests that indoxyl sulfate is implicated via novel mechanisms, including progenitor cell-related neovascularization and tissue factor-related hypercoagulability. These findings raise the possibility that strategies targeting serum indoxyl sulfate may have the potential to improve the outcomes of PAD and dialysis vascular access in patients with CKD. PMID:28067862

  4. Impact of Indoxyl Sulfate on Progenitor Cell-Related Neovascularization of Peripheral Arterial Disease and Post-Angioplasty Thrombosis of Dialysis Vascular Access.

    PubMed

    Wu, Chih-Cheng; Hung, Szu-Chun; Kuo, Ko-Lin; Tarng, Der-Cherng

    2017-01-07

    Patients with chronic kidney disease (CKD) have an increased risk of vascular disease, which is associated with considerable health care costs. Vascular disease in CKD differs clinically and pathobiologically from that in patients with normal renal function. Besides the traditional risk factors, retention of uremic toxins contributes to the pathogenesis of vascular disease in patients with CKD. Indoxyl sulfate is a protein-bound uremic toxin and is inefficiently removed by conventional dialysis. Accumulating evidence suggests that indoxyl sulfate is a vascular toxin involved in atherosclerosis, arteriosclerosis, vascular calcification and vascular repair. Clinically, indoxyl sulfate is associated with total and cardiovascular mortality in patients with CKD. Recent studies have indicated that in addition to coronary and cerebral arteries, indoxyl sulfate plays a role in peripheral artery disease (PAD) and dialysis graft thrombosis. Emerging evidence suggests that indoxyl sulfate is implicated via novel mechanisms, including progenitor cell-related neovascularization and tissue factor-related hypercoagulability. These findings raise the possibility that strategies targeting serum indoxyl sulfate may have the potential to improve the outcomes of PAD and dialysis vascular access in patients with CKD.

  5. Chronic rapamycin restores brain vascular integrity and function through NO synthase activation and improves memory in symptomatic mice modeling Alzheimer's disease

    PubMed Central

    Lin, Ai-Ling; Zheng, Wei; Halloran, Jonathan J; Burbank, Raquel R; Hussong, Stacy A; Hart, Matthew J; Javors, Martin; Shih, Yen-Yu Ian; Muir, Eric; Solano Fonseca, Rene; Strong, Randy; Richardson, Arlan G; Lechleiter, James D; Fox, Peter T; Galvan, Veronica

    2013-01-01

    Vascular pathology is a major feature of Alzheimer's disease (AD) and other dementias. We recently showed that chronic administration of the target-of-rapamycin (TOR) inhibitor rapamycin, which extends lifespan and delays aging, halts the progression of AD-like disease in transgenic human (h)APP mice modeling AD when administered before disease onset. Here we demonstrate that chronic reduction of TOR activity by rapamycin treatment started after disease onset restored cerebral blood flow (CBF) and brain vascular density, reduced cerebral amyloid angiopathy and microhemorrhages, decreased amyloid burden, and improved cognitive function in symptomatic hAPP (AD) mice. Like acetylcholine (ACh), a potent vasodilator, acute rapamycin treatment induced the phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and NO release in brain endothelium. Administration of the NOS inhibitor L-NG-Nitroarginine methyl ester reversed vasodilation as well as the protective effects of rapamycin on CBF and vasculature integrity, indicating that rapamycin preserves vascular density and CBF in AD mouse brains through NOS activation. Taken together, our data suggest that chronic reduction of TOR activity by rapamycin blocked the progression of AD-like cognitive and histopathological deficits by preserving brain vascular integrity and function. Drugs that inhibit the TOR pathway may have promise as a therapy for AD and possibly for vascular dementias. PMID:23801246

  6. Chronic rapamycin restores brain vascular integrity and function through NO synthase activation and improves memory in symptomatic mice modeling Alzheimer's disease.

    PubMed

    Lin, Ai-Ling; Zheng, Wei; Halloran, Jonathan J; Burbank, Raquel R; Hussong, Stacy A; Hart, Matthew J; Javors, Martin; Shih, Yen-Yu Ian; Muir, Eric; Solano Fonseca, Rene; Strong, Randy; Richardson, Arlan G; Lechleiter, James D; Fox, Peter T; Galvan, Veronica

    2013-09-01

    Vascular pathology is a major feature of Alzheimer's disease (AD) and other dementias. We recently showed that chronic administration of the target-of-rapamycin (TOR) inhibitor rapamycin, which extends lifespan and delays aging, halts the progression of AD-like disease in transgenic human (h)APP mice modeling AD when administered before disease onset. Here we demonstrate that chronic reduction of TOR activity by rapamycin treatment started after disease onset restored cerebral blood flow (CBF) and brain vascular density, reduced cerebral amyloid angiopathy and microhemorrhages, decreased amyloid burden, and improved cognitive function in symptomatic hAPP (AD) mice. Like acetylcholine (ACh), a potent vasodilator, acute rapamycin treatment induced the phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and NO release in brain endothelium. Administration of the NOS inhibitor L-NG-Nitroarginine methyl ester reversed vasodilation as well as the protective effects of rapamycin on CBF and vasculature integrity, indicating that rapamycin preserves vascular density and CBF in AD mouse brains through NOS activation. Taken together, our data suggest that chronic reduction of TOR activity by rapamycin blocked the progression of AD-like cognitive and histopathological deficits by preserving brain vascular integrity and function. Drugs that inhibit the TOR pathway may have promise as a therapy for AD and possibly for vascular dementias.

  7. The primary vascular dysregulation syndrome: implications for eye diseases

    PubMed Central

    2013-01-01

    Vascular dysregulation refers to the regulation of blood flow that is not adapted to the needs of the respective tissue. We distinguish primary vascular dysregulation (PVD, formerly called vasospastic syndrome) and secondary vascular dysregulation (SVD). Subjects with PVD tend to have cold extremities, low blood pressure, reduced feeling of thirst, altered drug sensitivity, increased pain sensitivity, prolonged sleep onset time, altered gene expression in the lymphocytes, signs of oxidative stress, slightly increased endothelin-1 plasma level, low body mass index and often diffuse and fluctuating visual field defects. Coldness, emotional or mechanical stress and starving can provoke symptoms. Virtually all organs, particularly the eye, can be involved. In subjects with PVD, retinal vessels are stiffer and more irregular, and both neurovascular coupling and autoregulation capacity are reduced while retinal venous pressure is often increased. Subjects with PVD have increased risk for normal-tension glaucoma, optic nerve compartment syndrome, central serous choroidopathy, Susac syndrome, retinal artery and vein occlusions and anterior ischaemic neuropathy without atherosclerosis. Further characteristics are their weaker blood–brain and blood-retinal barriers and the higher prevalence of optic disc haemorrhages and activated astrocytes. Subjects with PVD tend to suffer more often from tinnitus, muscle cramps, migraine with aura and silent myocardial ischaemic and are at greater risk for altitude sickness. While the main cause of vascular dysregulation is vascular endotheliopathy, dysfunction of the autonomic nervous system is also involved. In contrast, SVD occurs in the context of other diseases such as multiple sclerosis, retrobulbar neuritis, rheumatoid arthritis, fibromyalgia and giant cell arteritis. Taking into consideration the high prevalence of PVD in the population and potentially linked pathologies, in the current article, the authors provide

  8. Peripheral vascular disease: correlation of MR imaging and angiography

    SciTech Connect

    Wesbey, G.E.; Higgins, C.B.; Amparo, E.G.; Hale, J.D.; Kaufman, L.; Pogany, A.C.

    1985-09-01

    The capability of magnetic resonance (MR) imaging for detecting aortic, iliac, and femoral stenoses and occlusions was evaluated. Multisection spin-echo studies at 0.35 tesla were obtained of the infrarenal aorta to the femoral bifurcation in 24 patients, all of whom had undergone intraarterial angiography within 14 days of imaging. Transaxial MR images were compared with the angiograms. Arterial stenoses and occlusions in these vessels detected by MR imaging correlated with angiographic findings in 91% of the instances. Due to the limited spatial resolution, MR images failed to demonstrate some femoral stenoses. MR imaging may be used for evaluation of aortoiliac vascular disease and for follow-up study after surgical revascularization. However, the limited spatial resolution, noncomposite display of the aortoiliofemoral circulation, and lack of evaluation of peripheral runoff provided by current MR imaging techniques militate against its replacing angiography prior to vascular intervention.

  9. Cerebral small vessel disease and risk of death, ischemic stroke, and cardiac complications in patients with atherosclerotic disease: the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study.

    PubMed

    Conijn, Mandy M A; Kloppenborg, Raoul P; Algra, Ale; Mali, Willem P Th M; Kappelle, L Jaap; Vincken, Koen L; van der Graaf, Yolanda; Geerlings, Mirjam I

    2011-11-01

    Cerebral small vessel disease may be related to vascular and nonvascular pathology. We assessed whether lacunar infarcts and white matter lesions on MRI increased the risk of vascular and nonvascular death and future vascular events in patients with atherosclerotic disease. Brain MRI was performed in 1309 patients with atherosclerotic disease from the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study. Infarcts were scored visually and volumetric assessment of white matter lesion was performed. Patients were followed for a median of 4.5 years (range, 0.2 to 7.1 years) for death, ischemic stroke, and ischemic cardiac complications. Cox regression models showed that presence of lacunar infarcts (n=229) increased the risk of vascular (hazard ratio, 2.6; 95% CI, 1.4 to 4.9) and nonvascular death (hazard ratio, 2.7; 95% CI, 1.3 to 5.3), adjusted for age, sex, vascular risk factors, nonlacunar infarcts, and white matter lesion. These risks were similar for patients with silent lacunar infarcts. White matter lesion volume (relative to total intracranial volume) increased the risk of vascular death (hazard ratio per milliliter increase, 1.03; 95% CI, 1.01 to 1.05) and white matter lesions in the upper quintile compared with lower quintiles increased risk of ischemic stroke (hazard ratio, 2.6; 95% CI, 1.3 to 4.9). Cerebral small vessel disease, with or without a history of cerebrovascular disease, is associated with increased risk of death and ischemic stroke in patients with atherosclerotic disease.

  10. Diffuse and uncontrolled vascular smooth muscle cell proliferation in rapidly progressing pediatric moyamoya disease.

    PubMed

    Reid, Amy J; Bhattacharjee, Meenakshi B; Regalado, Ellen S; Milewicz, Allen L; El-Hakam, Lisa M; Dauser, Robert C; Milewicz, Dianna M

    2010-09-01

    Moyamoya disease is a rare stroke syndrome of unknown etiology resulting from stenosis or occlusion of the supraclinoid internal carotid artery (ICA) in association with an abnormal vascular network in the basal ganglia. Although the highest incidence of moyamoya disease is in pediatric patients, pathology reports have been primarily limited to adult samples and describe occlusive fibrocellular lesions in the intimae of affected arteries. We describe the case of a young girl with primary moyamoya disease who presented at 18 months of age with right hemiparesis following an ischemic stroke. Angiography showed stenosis of the distal left ICA, left middle cerebral artery, and right ICA. An emergent left-sided dural inversion was performed. Recurrent strokes and alternating hemiplegia necessitated a right dural inversion 6 months later. Nonetheless, her aggressive disease proved uniquely refractory to surgical revascularization, and she succumbed to recurrent strokes and neurological deterioration at 2.5 years of age. Pathological specimens revealed a striking bilateral occlusion of the anterior carotid circulation resulting from intimal proliferation of smooth muscle cells (SMCs). Most strikingly, the ascending aorta and the superior mesenteric artery demonstrated similar intimal proliferation, along with SMC proliferation in the media. The systemic pathology involving multiple arteries in this extremely young child, the first case of its kind available for autopsy, suggests that globally uncontrolled SMC proliferation, in the absence of environmental risk factors and likely resulting from an underlying genetic alteration, may be a primary etiologic event leading to moyamoya disease.

  11. Vascular Aging: Implications for Cardiovascular Disease and Therapy

    PubMed Central

    Ghebre, Yohannes T; Yakubov, Eduard; Wong, Wing Tak; Krishnamurthy, Prasanna; Sayed, Nazish; Sikora, Andrew G; Bonnen, Mark D

    2017-01-01

    The incidence and prevalence of cardiovascular disease is highest among the elderly, in part, due to deleterious effects of advancing age on the heart and blood vessels. Aging, a known cardiovascular risk factor, is progressively associated with structural and functional changes to the vasculature including hemodynamic disturbance due to increased oxidative stress, premature cellular senescence and impairments in synthesis and/or secretion of endothelium-derived vasoactive molecules. These molecular and physiological changes lead to vessel wall stiffening and thickening, as well as other vascular complications that culminate to loss of vascular tone regulation and endothelial function. Intriguingly, the vessel wall, a biochemically active structure composed of collagen, connective tissue, smooth muscle and endothelial cells, is adversely affected by processes involved in premature or normal aging. Notably, the inner most layer of the vessel wall, the endothelium, becomes senescent and dysfunctional with advancing age. As a result, its ability to release vasoactive molecules such as acetylcholine (ACh), prostacyclin (PGI2), endothelium-derived hyperpolarizing factor (EDHF), and nitric oxide (NO) is reduced and the cellular response to these molecules is also impaired. By contrast, the vascular endothelium increases its generation and release of reactive oxygen (ROS) and nitrogen (RNS) species, vasoconstrictors such as endothelin (ET) and angiotensin (AT), and endogenous inhibitors of NO synthases (NOSs) to block NO. This skews the balance of the endothelium in favor of the release of highly tissue reactive and harmful molecules that promote DNA damage, telomere erosion, senescence, as well as stiffened and hardened vessel wall that is prone to the development of hypertension, diabetes, atherosclerosis and other cardiovascular risk factors. This Review discusses the impact of advancing age on cardiovascular health, and highlights the cellular and molecular mechanisms

  12. [Application of multislice CT for the diagnosis of cerebro-vascular disease].

    PubMed

    Katada, Kazuhiro

    2004-11-01

    Introduction of multislice CT (MSCT) has revolutionizing the diagnosis of cerebro-vascular disease. Newly developed 32-slice MSCT enabled us to acquire isotropic volumetric data of whole brain with the resolution of 0.5-mm. CT perfusion is one of the promising application for the diagnosis of early-staged cerebral ischemia. However, it can be hazardous in terms of ionic radiation because of multiplied exposure to the same level. A new quantum denoising filter was developed in order to solve this problem. It is possible to reduce more than 80% of dose using the filter in combination with lower kv/lower mA technique. This filter can also aids to improve the detection of early CT signs, which is important for the diagnosis of cerebral ischemia. Detection of the penumbra can be made by revealing the absence of early CT sign and low perfusion area in CT perfusion. Isotropic volumetric data provided by MSCA can also be an ideal source data for the high-quality 3D-CT angiography. Improved temporal resolution of MSCT in obtaining volumetric data made it possible separated visualization of arteries and veins on single 3D-CTA image. The technique to visualize brain surface using isotropic data and volume rendering algorithm was also reported.

  13. Optical Assessment of Vascular Disease Progression and Treatment

    NASA Astrophysics Data System (ADS)

    Samuels, Joshua A.

    Vascular disease manifests itself in many different forms, including chronic ulcers which do not heal, impaired blood flow to the limbs, or damage to the natural reperfusion process. The current forms of assessing vascular disease are often subjective and provide incomplete knowledge about the tissue of interest. This work focused on developing non-invasive techniques to quantitatively evaluate three specific elements of vascular disease: diabetic ulcers, venous ulcers, and peripheral arterial disease. Diffuse Near Infrared Spectroscopy (DNIRS) was used to predict healing (82% positive predictive value) in diabetic ulcers after 4 weeks of assessment (sensitivity of 0.9 and specificity of 0.86; p<0.002), proving to be an alternative and superior method to wound size reduction alone (the current gold standard). A novel therapeutic ultrasound treatment for venous ulcers, using a low-frequency (20kHz), low intensity (<100mW/cm2 ISPTP), fully-wearable applicator, was assessed using DNIRS and Diffuse Correlation Spectroscopy (DCS), wherein it was established that capillary flow changes over time in healing venous ulcers compared to wounds which do not heal (p<0.01). It was also determined that the ultrasound therapy was successful at improving wound outcomes, specifically the rate of wound closure per week (p<0.05 for wound size, p<0.01 for optical data). Finally, DNIRS and DCS were used in conjunction to assess the reactive hyperemic response in patients with suspected Peripheral Arterial Disease (PAD). It was found that the time between the release of cuff occlusion in the diseased limb and the first peak of reperfusion (flow mediated dilatation) correlated to PAD severity, with longer times (>30 seconds) belonging to patients with PAD (p<0.05). Additionally, it was discovered that the magnitude of the reperfusion did not relate to PAD, but rather to tobacco use. Patients who smoked had reduced hyperemic responses (p<0.02), whether or not they had PAD. Overall, this

  14. Ambulatory arterial stiffness index is not associated with magnetic resonance imaging markers of cerebral small vessel disease in lacunar stroke patients.

    PubMed

    Klarenbeek, Pim; van Oostenbrugge, Robert J; Staals, Julie

    2015-05-01

    Ambulatory arterial stiffness index (AASI) is associated with microvascular damage in other organs, but the association with microvascular brain damage is unknown. The association of AASI with magnetic resonance imaging (MRI) markers of cerebral small vessel disease in 143 patients with lacunar stroke was investigated. We performed 24-hour ambulatory blood pressure monitoring and scored the presence of lacunes, white matter hyperintensities, perivascular spaces, and cerebral microbleeds on brain MRI. In logistic regression analyses, AASI was associated with white matter hyperintensities, but, after adjustment for age and sex, this association lost significance. AASI was not associated with lacunes, microbleeds, or perivascular spaces. Systolic and diastolic 24-hour blood pressure values were associated with lacunes, perivascular spaces, and microbleeds independent of age and sex. Despite its significance and growing interest as a possible prognostic and therapeutic target in (micro)vascular diseases, AASI seems to have no added value over standard 24-hour blood pressure in cerebral small vessel disease.

  15. Role of Multimodal Evaluation of Cerebral Hemodynamics in Selecting Patients with Symptomatic Carotid or Middle Cerebral Artery Steno-occlusive Disease for Revascularization

    PubMed Central

    Sharma, Vijay K; Tsivgoulis, Georgios; Ning, Chou; Teoh, Hock L; Bairaktaris, Chrisostomos; Chong, Vincent FH; Ong, Benjamin KC; Chan, Bernard PL; Sinha, Arvind K

    2008-01-01

    Background: The circle of Willis provides collateral pathways to perfuse the affected vascular territories in patients with severe stenoocclusive disease of major arteries. The collateral perfusion may become insufficient in certain physiological circumstances due to failed vasodilatory reserve and intracranial steal phenomenon, so-called ‘Reversed-Robinhood syndrome’. We evaluated cerebral hemodynamics and vasodilatory reserve in patients with symptomatic distal internal carotid (ICA) or middle cerebral artery (MCA) severe steno-occlusive disease. Methods: Diagnostic transcranial Doppler (TCD) and TCD-monitoring with voluntary breath-holding according to a standard scanning protocol were performed in patients with severe ICA or MCA steno-occlusive disease. The steal phenomenon was detected as transient, spontaneous, or vasodilatory stimuli-induced velocity reductions in affected arteries at the time of velocity increase in normal vessels. Patients with exhausted vasomotor reactivity and intracranial steal phenomenon during breath-holding were further evaluated by 99technetiumm-hexamethyl propylene amine oxime single photon emission computed tomography (HMPAO-SPECT) with acetazolamide challenge. Results: Sixteen patients (age 27–74 years, 11 men) fulfilled our TCD criteria for exhausted vasomotor reactivity and intracranial steal phenomenon during the standard vasomotor testing by breath holding. Acetazolamide-challenged HMPAO-SPECT demonstrated significant hypoperfusion in 12 patients in affected arterial territories, suggestive of failed vasodilatory reserve. A breath-holding index of ≤0.3 on TCD was associated with an abnormal HMPAO-SPECT with acetazolamide challenge. TCD findings of a breath holding index of ≤0.3 and intracranial steal during the procedure were determinants of a significant abnormality on HMPAO-SPECT with acetazolamide challenge. Conclusion: Multimodal evaluation of cerebral hemodynamics in symptomatic patients with severe steno

  16. Role of Multimodal Evaluation of Cerebral Hemodynamics in Selecting Patients with Symptomatic Carotid or Middle Cerebral Artery Steno-occlusive Disease for Revascularization.

    PubMed

    Sharma, Vijay K; Tsivgoulis, Georgios; Ning, Chou; Teoh, Hock L; Bairaktaris, Chrisostomos; Chong, Vincent Fh; Ong, Benjamin Kc; Chan, Bernard Pl; Sinha, Arvind K

    2008-10-01

    The circle of Willis provides collateral pathways to perfuse the affected vascular territories in patients with severe stenoocclusive disease of major arteries. The collateral perfusion may become insufficient in certain physiological circumstances due to failed vasodilatory reserve and intracranial steal phenomenon, so-called 'Reversed-Robinhood syndrome'. We evaluated cerebral hemodynamics and vasodilatory reserve in patients with symptomatic distal internal carotid (ICA) or middle cerebral artery (MCA) severe steno-occlusive disease. Diagnostic transcranial Doppler (TCD) and TCD-monitoring with voluntary breath-holding according to a standard scanning protocol were performed in patients with severe ICA or MCA steno-occlusive disease. The steal phenomenon was detected as transient, spontaneous, or vasodilatory stimuli-induced velocity reductions in affected arteries at the time of velocity increase in normal vessels. Patients with exhausted vasomotor reactivity and intracranial steal phenomenon during breath-holding were further evaluated by (99)technetium(m)-hexamethyl propylene amine oxime single photon emission computed tomography (HMPAO-SPECT) with acetazolamide challenge. Sixteen patients (age 27-74 years, 11 men) fulfilled our TCD criteria for exhausted vasomotor reactivity and intracranial steal phenomenon during the standard vasomotor testing by breath holding. Acetazolamide-challenged HMPAO-SPECT demonstrated significant hypoperfusion in 12 patients in affected arterial territories, suggestive of failed vasodilatory reserve. A breath-holding index of ≤0.3 on TCD was associated with an abnormal HMPAO-SPECT with acetazolamide challenge. TCD findings of a breath holding index of ≤0.3 and intracranial steal during the procedure were determinants of a significant abnormality on HMPAO-SPECT with acetazolamide challenge. Multimodal evaluation of cerebral hemodynamics in symptomatic patients with severe steno-occlusive disease of the ICA or MCA is helpful in

  17. Immunosuppression Related to Collagen-Vascular Disease or Its Treatment

    PubMed Central

    Hamilton, Carol Dukes

    2005-01-01

    Collagen-vascular diseases are associated with immune dysregulation and inflammation, leading to tissue destruction or compromise. Immunosuppression is more commonly associated with the drugs used to treat these disorders than with the diseases themselves. The newest agents being used to treat collagen-vascular diseases are the tumor necrosis factor (TNF)-α inhibitors. U.S. Food and Drug Administration–approved TNF-α inhibitors have differing effects on the immune system, reflecting their potency and mechanisms of action. They are particularly effective in breaking down granulomatous inflammation, which makes them effective treatment for sarcoidosis and Wegener's granulomatosis. This same property makes them likely to break down the host defense mechanism that normally contains pathogens such as mycobacteria and fungi in a dormant state, namely the physical and immunologic barrier formed by granulomas in the lung and elsewhere. The most common infection reported with the TNF-α inhibitors has been tuberculosis, which may manifest as pulmonary and/or extrapulmonary disease, with the latter being more common and severe than usual. Histoplasma capsulatum, Aspergillus, Cryptococcus neoformans, and Listeria monocytogenes have also been described in a number of cases, and their frequency is discussed. PMID:16322600

  18. Extracellular nucleotide and nucleoside signaling in vascular and blood disease

    PubMed Central

    Idzko, Marco; Ferrari, Davide; Riegel, Ann-Kathrin

    2014-01-01

    Nucleotides and nucleosides—such as adenosine triphosphate (ATP) and adenosine—are famous for their intracellular roles as building blocks for the genetic code or cellular energy currencies. In contrast, their function in the extracellular space is different. Here, they are primarily known as signaling molecules via activation of purinergic receptors, classified as P1 receptors for adenosine or P2 receptors for ATP. Because extracellular ATP is rapidly converted to adenosine by ectonucleotidase, nucleotide-phosphohydrolysis is important for controlling the balance between P2 and P1 signaling. Gene-targeted mice for P1, P2 receptors, or ectonucleotidase exhibit only very mild phenotypic manifestations at baseline. However, they demonstrate alterations in disease susceptibilities when exposed to a variety of vascular or blood diseases. Examples of phenotypic manifestations include vascular barrier dysfunction, graft-vs-host disease, platelet activation, ischemia, and reperfusion injury or sickle cell disease. Many of these studies highlight that purinergic signaling events can be targeted therapeutically. PMID:25001468

  19. Apolipoprotein (a) concentrations and susceptibility to coronary artery disease in patients with peripheral vascular disease.

    PubMed Central

    Groves, P; Rees, A; Bishop, A; Morgan, R; Ruttley, M; Lewis, N; Lane, I; Hall, R

    1993-01-01

    OBJECTIVE--To investigate the relation between apolipoprotein(a) concentrations and angiographically defined coronary artery disease in patients with atheromatous peripheral vascular disease. DESIGN--40 consecutive patients were recruited at the time of admission for peripheral vascular surgery. All underwent clinical assessment and coronary arteriography. Apolipoprotein(a) concentrations were measured by an immunoradiometric assay. SETTING--Tertiary referral centre. SUBJECTS--Patients requiring surgical intervention for large vessel peripheral vascular disease. MAIN OUTCOME MEASURES--Presence or absence and severity and distribution of angiographically defined coronary artery disease. Measurement of circulating contractions of apolipoprotein(a) and other lipid indices. RESULTS--Coronary artery disease was absent in 11 patients (group 1), mild to moderate in 12 (group 2), and severe in 17 (group 3). The distribution of peripheral vascular disease and of standard lipid indices was similar in these three groups of patients. There was a significant difference in apolipoprotein(a) concentrations between the three groups, with concentrations progressively increasing with the severity of coronary artery disease (mean (95% confidence interval): group 1, 112 U/1 (52 to 242); group 2, 214 U/1 (129 to 355); group 3, 537 U/1 (271 to 1064) (analysis of variance p < 0.005). The prevalence of coronary artery disease was increased 7.4 fold in patients with apolipoprotein(a) concentrations that were greater than the cohort median (206 U/1) (p < 0.01). CONCLUSIONS--The results show an association between apolipoprotein(a) concentrations and angiographically defined coronary artery disease in patients with large vessel peripheral vascular disease. The findings imply differences in the pathogenesis of coronary and peripheral atheroma and suggest that the measurement of apolipoprotein(a) may prove a useful additional tool in the risk factor assessment of patients undergoing peripheral

  20. Structural network connectivity and cognition in cerebral small vessel disease.

    PubMed

    Tuladhar, Anil M; van Dijk, Ewoud; Zwiers, Marcel P; van Norden, Anouk G W; de Laat, Karlijn F; Shumskaya, Elena; Norris, David G; de Leeuw, Frank-Erik

    2016-01-01

    Cerebral small vessel disease (SVD), including white matter hyperintensities (WMH), lacunes and microbleeds, and brain atrophy, are related to cognitive impairment. However, these magnetic resonance imaging (MRI) markers for SVD do not account for all the clinical variances observed in subjects with SVD. Here, we investigated the relation between conventional MRI markers for SVD, network efficiency and cognitive performance in 436 nondemented elderly with cerebral SVD. We computed a weighted structural connectivity network from the diffusion tensor imaging and deterministic streamlining. We found that SVD-severity (indicated by higher WMH load, number of lacunes and microbleeds, and lower total brain volume) was related to networks with lower density, connection strengths, and network efficiency, and to lower scores on cognitive performance. In multiple regressions models, network efficiency remained significantly associated with cognitive index and psychomotor speed, independent of MRI markers for SVD and mediated the associations between these markers and cognition. This study provides evidence that network (in)efficiency might drive the association between SVD and cognitive performance. This highlights the importance of network analysis in our understanding of SVD-related cognitive impairment in addition to conventional MRI markers for SVD and might provide an useful tool as disease marker.

  1. Diagonal Earlobe Crease (Frank's Sign): A Predictor of Cerebral Vascular Events.

    PubMed

    Nazzal, Saleh; Hijazi, Basem; Khalila, Luai; Blum, Arnon

    2017-04-29

    Frank's sign was first described in 1973 by an American physician (Sonders T. Frank). It is a diagonal crease in the earlobe that starts from the tragus to the edge of the auricle in an angle of 45° in varying depths. Frank's sign was described as a predictor of future coronary heart disease and peripheral vascular diseases. The aim of the study was to examine the association between Frank's sign and the development of ischemic stroke. This was a prospective study that enrolled consecutive patients admitted with an acute ischemic stroke. Frank's sign was tested in both ears. Clinical data included age, gender, type 2 diabetes mellitus, and hypertension. The study was approved by the institutional review board (the institutional ethics committee). A total of 241 consecutive patients who were hospitalized with an acute stroke and were eligible to take part in the study were recruited. Frank's sign was present in 190 patients (78.8%). Patients were divided according to clinical findings and the findings from brain computed tomography. There were 153 patients with transient ischemic attacks (63.6% of the patients) and 88 with cerebrovascular accidents (36.4% of the patients). A total of 112 patients with transient ischemic attacks had Frank's sign (73.2%), and 78 patients with cerebrovascular accidents had Frank's sign (88.6%), with a statistically significant difference (P <.01). Frank's sign could predict ischemic cerebrovascular events. Patients with classical cardiovascular risk factors had Frank's sign at a higher frequency. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Exercise, vascular wall and cardiovascular diseases: an update (Part 1).

    PubMed

    Leung, Fung Ping; Yung, Lai Ming; Laher, Ismail; Yao, Xiaoqiang; Chen, Zhen Yu; Huang, Yu

    2008-01-01

    Cardiovascular disease (CVD) remains the leading cause of morbidity and premature mortality in both women and men in most industrialized countries, and has for some time also established a prominent role in developing nations. In fact, obesity, diabetes mellitus and hypertension are now commonplace even in children and youths. Regular exercise is rapidly gaining widespread advocacy as a preventative measure in schools, medical circles and in the popular media. There is overwhelming evidence garnered from a number of sources, including epidemiological, prospective cohort and intervention studies, suggesting that CVD is largely a disease associated with physical inactivity. A rapidly advancing body of human and animal data confirms an important beneficial role for exercise in the prevention and treatment of CVD. In Part 1 of this review we discuss the impact of exercise on CVD, and we highlight the effects of exercise on (i) endothelial function by regulation of endothelial genes mediating oxidative metabolism, inflammation, apoptosis, cellular growth and proliferation, increased superoxide dismutase (SOD)-1, down-regulation of p67phox, changes in intracellular calcium level, increased vascular endothelial nitric oxide synthase (eNOS), expression and eNOS Ser-1177 phosphorylation; (ii) vascular smooth muscle function by either an increased affinity of the Ca2+ extrusion mechanism or an augmented Ca2+ buffering system by the superficial sarcoplasmic reticulum to increase Ca2+ sequestration, increase in K+ channel activity and/or expression, and increase in L-type Ca2+ current density; (iii) antioxidant systems by elevation of Mn-SOD, Cu/Zn-SOD and catalase, increases in glutathione peroxidase activity and activation of vascular nicotinamide adenine dinucleotide phosphate [(NAD(P)H] oxidase and p22phox expression; (iv) heat shock protein (HSP) expression by stimulating HSP70 expression in myocardium, skeletal muscle and even in human leucocytes, probably through heat

  3. Vascular Function, Cerebral Cortical Thickness, and Cognitive Performance in Middle-Aged Hispanic and Non-Hispanic Caucasian Adults

    PubMed Central

    Pasha, Evan; Kaur, Sonya S.; Gonzales, Mitzi M.; Machin, Daniel R.; Kasischke, Kennon; Tanaka, Hirofumi; Haley, Andreana P.

    2015-01-01

    Hispanics are at increased risk of acquiring cardiovascular risk factors that contribute to cognitive dysfunction. To compare indices of vascular health to measures of cerebral gray matter integrity, 60 middle-aged Hispanic and non-Hispanic Caucasian participants were matched across age, gender, years of education, and mental status. Arterial stiffness was characterized via β-stiffness index and carotid-femoral pulse-wave velocity, and magnetic resonance imaging estimated cortical thickness in a priori regions of interest known to be susceptible to vascular risk factors. Measures of arterial stiffness were significantly higher in Hispanics than in non-Hispanic Caucasians. Hispanics exhibited thinner left inferior frontal gyrus (LIFG) cortical thickness (p=0.04) with concurrently lower language (p=0.02), memory (p=0.03), and attention-executive functioning (p=0.02). These results suggest that compromised vascular health may occur simultaneously with cortical thinning of the LIFG as an early neuropathological alteration in Hispanics. PMID:25720950

  4. Ultrastructural cutaneous microvascular pathology of young adults aged up to 50 years with chronic kidney disease and vascular cognitive impairment.

    PubMed

    Arismendi-Morillo, Gabriel; Fernández-Abreu, Mary

    2010-08-01

    Studies suggest a link between chronic kidney disease and cognitive impairment. Skin biopsy is hire in the study of leucoaraiosis since permit establish the responsible vascular pathology of subcortical white matter changes because the pathological hallmark is systemic. The aim was to study the ultrastructural changes of cutaneous small vessel of patients aged up to 50 years with chronic kidney disease (CKD) and vascular cognitive impairment (VCI). Clinical, laboratorial, cerebral imaging, neuropsycological evaluation for executive functions (Clox test), and skin biopsy to 4 patients aged up to 50 years with CKD and VCI were done. Skin biopsy was prepared for conventional transmission electron microscopy study. Clinical diagnosis included hypertension, diabetes, and CKD in all cases. All cases developed VCI in a relatively short period. Small vessels study revealed small vessel disease type-degenerative microangiopathy. The principal findings were increase of wall-lumen ratio, thickened basal membrane, and collagen fibers proliferation. Cutaneous degenerative microangiopathy is matched with cerebral microvascular pathology and could be important for the development of cognitive impairment in young adults with CKD. The characterization of microvascular pathology in skin biopsies, in this type of patients, could contribute to the knowledge of some pathophysiological and therapeutical topics and possibly be useful in clinical setting. Added patients are needed to establish a complete characterization of microangiopathy.

  5. Vascular calcification in chronic kidney disease: Pathogenesis and clinical implication.

    PubMed

    Disthabanchong, Sinee

    2012-04-06

    Cardiovascular disease is the leading cause of death among patients with chronic kidney disease (CKD). Vascular calcification (VC) is one of the independent risk factors associated with cardiovascular disease and cardiovascular mortality in both the general population and CKD patients. Earlier evidence revealed substantially higher prevalence of VC in young adults on chronic hemodialysis compared to the general population in the same age range, indicating the influence of CKD-related risk factors on the development of VC. Pathogenesis of VC involves an active, highly organized cellular transformation of vascular smooth muscle cells to bone forming cells evidenced by the presence of bone matrix proteins in the calcified arterial wall. VC occurs in both the intima and the media of arterial wall with medial calcification being more prevalent in CKD. In addition to traditional cardiovascular risks, risk factors specific to CKD such as phosphate retention, excess of calcium, history of dialysis, active vitamin D therapy in high doses and deficiency of calcification inhibitors play important roles in promoting the development of VC. Non-contrast multi-slice computed tomography has often been used to detect coronary artery calcification. Simple plain radiographs of the lateral lumbar spine and pelvis can also detect VC in the abdominal aorta and femoral and iliac arteries. Currently, there is no specific therapy to reverse VC. Reduction of calcium load, lowering phosphate retention using non-calcium containing phosphate binders, and moderate doses of active vitamin D may attenuate progression. Parenteral sodium thiosulfate has also been shown to delay VC progression.

  6. Regulation and involvement of matrix metalloproteinases in vascular diseases

    PubMed Central

    Amin, Matthew; Pushpakumar, Sathnur; Muradashvili, Nino; Kundu, Sourav; Tyagi, Suresh C.; Sen, Utpal

    2017-01-01

    Matrix metalloproteinases (MMPs) are a family of zinc dependent endopeptidases whose main function is to degrade and deposit structural proteins within the extracellular matrix (ECM). A dysregulation of MMPs is linked to vascular diseases. MMPs are classified into collagenases, gelatinases, membrane-type, metalloelastase, stromelysins, matrilysins, enamelysins, and unclassified subgroups. The production of MMPs is stimulated by factors such as oxidative stress, growth factors and inflammation which lead to its up- or down-regulation with subsequent ECM remodeling. Normally, excess activation of MMPs is controlled by their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). An imbalance of MMPs and TIMPs has been implicated in hypertension, atherosclerotic plaque formation and instability, aortic aneurysms and varicose vein wall remodeling. Also, recent evidence suggests epigenetic regulation of some MMPs in angiogenesis and atherosclerosis. Over the years, pharmacological inhibitors of MMPs have been used to modify or prevent the development of the disease with some success. In this review, we discuss recent advances in MMP biology, and their involvement in the manifestation of vascular disease. PMID:26709763

  7. Percutaneous Transluminal Angioplasty in Peripheral Vascular Disease: A Review

    PubMed Central

    Louis, Eugene L. St.; Provan, John L.; Gray, Robin R.; Grosman, Harvey; Ameli, F. Michael; Elliott, David S.

    1982-01-01

    Percutaneous transluminal angioplasty is a relatively new technique employed in the treatment of stenoses or occlusions of peripheral arteries. While the longterm success rates have yet to be determined, short-term results have been excellent. The procedure has greatest value in the dilatation of localized lesions, avoiding surgery and its attendant risks. However, PTA and surgery are complementary, not competing, modes of therapy. PTA complements the traditional therapy of peripheral vascular disease, which remains reconstructive surgery. ImagesFig. 7Fig. 8Fig. 9Fig. 10Fig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6 PMID:21286052

  8. Clinical applications of lightguide diffuse reflectance spectrophotometry in vascular disease

    NASA Astrophysics Data System (ADS)

    Harrison, David K.; Delaney, Colin; Brown, Linda; Newton, David J.; McCollum, Peter T.

    1994-02-01

    There is enormous potential for application of lightguide tissue reflectance spectrophotometry in the diagnosis and treatment of peripheral vascular disease. In the present study, measurements were carried out in 10 such pre-amputation patients to compare the use of micro-lightguide spectrophotometry with the macro-lightguide technique. These preliminary results show excellent agreement between the new, non-invasive micro-lightguide technique and the `gold standard' skin blood flow measurements. This technique could thus provide a more functional, non-invasive assessment of healing potential than skin blood flow measurement.

  9. Color vision test to differentiate Alzheimer's disease from vascular dementia.

    PubMed

    Kawada, Tomoyuki

    2017-10-01

    Arnaoutoglou et al. (2017) reported that "Ishihara Color Vision Test - 38 Plate" was useful for the differential diagnosis of dementia between Alzheimer's Disease (AD) and Vascular Dementia (VaD). The authors used sensitivity/specificity analysis, presenting 80.6% and 87.5% to discriminate AD and VaD patients when an optimal (32.5) cut-off value of performance was used. The authors cited a reference of the fact that AD patients suffered from a non-specific type of color blindness (Pache et al., 2003), and I have a query on their study with special reference to statistical method.

  10. Advances in non-invasive imaging of intracranial vascular disease.

    PubMed Central

    Jäger, H. R.; Grieve, J. P.

    2000-01-01

    Intra-arterial catheter angiography has, in the past, been the mainstay for the investigation of intracranial vascular disease. It is, however, invasive, usually requires in-patients admission, and is associated with a rate of neurological complications between 1% and 3%. In recent years, magnetic resonance angiography (MRA) and CT angiography (CTA) have emerged as non-invasive alternatives for imaging blood vessels and have made a significant impact on neuroradiological investigations. It is the purpose of this article to explain the basic technical principles of these two methods and to give an overview of their current clinical applications. PMID:10700757

  11. Reduced nitric oxide bioavailability mediates cerebroarterial dysfunction independent of cerebral amyloid angiopathy in a mouse model of Alzheimer's disease.

    PubMed

    Merlini, Mario; Shi, Yi; Keller, Stephan; Savarese, Gianluigi; Akhmedov, Alexander; Derungs, Rebecca; Spescha, Remo D; Kulic, Luka; Nitsch, Roger M; Lüscher, Thomas F; Camici, Giovanni G

    2017-02-01

    In Alzheimer's disease (AD), cerebral arteries, in contrast to cerebral microvessels, show both cerebral amyloid angiopathy (CAA) -dependent and -independent vessel wall pathology. However, it remains unclear whether CAA-independent vessel wall pathology affects arterial function, thereby chronically reducing cerebral perfusion, and, if so, which mechanisms mediate this effect. To this end, we assessed the ex vivo vascular function of the basilar artery and a similar-sized peripheral artery (femoral artery) in the Swedish-Arctic (SweArc) transgenic AD mouse model at different disease stages. Furthermore, we used quantitative immunohistochemistry to analyze CAA, endothelial morphology, and molecular pathways pertinent to vascular relaxation. We found that endothelium-dependent, but not smooth muscle-dependent, vasorelaxation was significantly impaired in basilar and femoral arteries of 15-mo-old SweArc mice compared with that of age-matched wild-type and 6-mo-old SweArc mice. This impairment was accompanied by significantly reduced levels of cyclic GMP, indicating a reduced nitric oxide (NO) bioavailability. However, no age- and genotype-related differences in oxidative stress as measured by lipid peroxidation were observed. Although parenchymal capillaries, arterioles, and arteries showed abundant CAA in the 15-mo-old SweArc mice, no CAA or changes in endothelial morphology were detected histologically in the basilar and femoral artery. Thus our results suggest that, in this AD mouse model, dysfunction of large intracranial, extracerebral arteries important for brain perfusion is mediated by reduced NO bioavailability rather than by CAA. This finding supports the growing body of evidence highlighting the therapeutic importance of targeting the cerebrovasculature in AD.

  12. Isometric Exercise Training for Managing Vascular Risk Factors in Mild Cognitive Impairment and Alzheimer’s Disease

    PubMed Central

    Hess, Nicole C. L.; Smart, Neil A.

    2017-01-01

    Alzheimer’s disease (AD) is the most common form of dementia diagnosed amongst the elderly. Mild cognitive impairment (MCI) is a condition often indicative of the earliest symptomatology of AD with 10%–15% of MCI patients reportedly progressing to a diagnosis of AD. Individuals with a history of vascular risk factors (VRF’s) are considered high risk candidates for developing cognitive impairment in later life. Evidence suggests that vascular injury resulting from untreated VRF’s promotes progression from MCI to AD and exacerbates the severity of dementia in AD, and neuroimaging studies have found that the neurodegenerative processes associated with AD are heavily driven by VRF’s that promote cerebral hypoperfusion. Subsequently, common links between vascular disorders such as hypertension and neurodegenerative disorders such as AD include compromised vasculature, cerebral hypoperfusion and chronic low grade inflammation (a hallmark of both hypertension and AD). Exercise has been demonstrated to be an effective intervention for blood pressure management, chronic low grade inflammation and improvements in cognition. Data from recent analyses suggests that isometric exercise training (IET) may improve vascular integrity and elicit blood pressure reductions in hypertensives greater than those seen with dynamic aerobic and resistance exercise. IET may also play an effective role in the management of VRF’s at the MCI stage of AD and may prove to be a significant strategy in the prevention, attenuation or delay of progression to AD. A plausible hypothesis is that the reactive hyperemia stimulated by IET initiates a cascade of vascular, neurotrophic and neuro-endocrine events that lead to improvements in cognitive function. PMID:28316570

  13. Cerebral compensation during motor imagery in Parkinson's disease.

    PubMed

    Helmich, Rick C; de Lange, Floris P; Bloem, Bastiaan R; Toni, Ivan

    2007-06-11

    In neurodegenerative disorders, neural damage can trigger compensatory mechanisms that minimize behavioural impairments. Here, we aimed at characterizing cerebral compensation during motor imagery in Parkinson's disease (PD), while controlling for altered motor execution and sensory feedback. We used a within-patient design to compare the most and least affected hand in 19 right-handed PD patients with markedly right-lateralized symptoms. We used a motor imagery (MI) task in which the patients were required to judge the laterality of hand images, rotated either in a lateral or in a medial orientation with respect to the body sagittal plane. This design allowed us to compare cerebral activity (using fMRI) evoked by MI of each hand separately, while objectively monitoring task performance. Reaction times and parieto-premotor activity increased in a similar manner as a function of stimulus rotation during motor imagery of left and right hands. However, patients were markedly slower when judging images of the affected hand in lateral orientations, and there was a corresponding increase in activity in the right extrastriate body area (EBA) and occipito-parietal cortex during mental rotation of the affected hand. Furthermore, these regions increased their connectivity towards the left PMd for right (affected) hands in a lateral orientation. We infer that, in strongly lateralized PD patients, motor imagery of the most-affected hand exploits additional resources in extrastriate visual areas. These findings characterize the cerebral bases of the increased dependence on visual information processing during the generation of motor plans in PD, pointing to its compensatory role.

  14. Doxycycline, a matrix metalloprotease inhibitor, reduces vascular remodeling and damage after cerebral ischemia in stroke-prone spontaneously hypertensive rats.

    PubMed

    Pires, Paulo W; Rogers, Curt T; McClain, Jonathon L; Garver, Hannah S; Fink, Gregory D; Dorrance, Anne M

    2011-07-01

    Matrix metalloproteases (MMPs) are a family of zinc peptidases involved in extracellular matrix turnover. There is evidence that increased MMP activity is involved in remodeling of resistance vessels in chronic hypertension. Thus we hypothesized that inhibition of MMP activity with doxycycline (DOX) would attenuate vascular remodeling. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were treated with DOX (50 mg·kg(-1)·day(-1) in the drinking water) for 6 wk. Untreated SHRSP were controls. Blood pressure was measured by telemetry during the last week. Middle cerebral artery (MCA) and mesenteric resistance artery (MRA) passive structures were assessed by pressure myography. MMP-2 expression in aortas was measured by Western blot. All results are means ± SE. DOX caused a small increase in mean arterial pressure (SHRSP, 154 ± 1; SHRSP + DOX, 159 ± 3 mmHg; P < 0.001). Active MMP-2 expression was reduced in aorta from SHRSP + DOX (0.21 ± 0.06 vs. 0.49 ± 0.13 arbitrary units; P < 0.05). In the MCA, at 80 mmHg, DOX treatment increased the lumen (273.2 ± 4.7 vs. 238.3 ± 6.3 μm; P < 0.05) and the outer diameter (321 ± 5.3 vs. 290 ± 7.6 μm; P < 0.05) and reduced the wall-to-lumen ratio (0.09 ± 0.002 vs. 0.11 ± 0.003; P < 0.05). Damage after transient cerebral ischemia (transient MCA occlusion) was reduced in SHRSP + DOX (20.7 ± 4 vs. 45.5 ± 5% of hemisphere infarcted; P < 0.05). In the MRA, at 90 mmHg DOX, reduced wall thickness (29 ± 1 vs. 22 ± 1 μm; P < 0.001) and wall-to-lumen ratio (0.08 ± 0.004 vs. 0.11 ± 0.008; P < 0.05) without changing lumen diameter. These results suggest that MMPs are involved in hypertensive vascular remodeling in both the peripheral and cerebral vasculature and that DOX reduced brain damage after cerebral ischemia.

  15. Renal vascular disease: pathology of large blood vessel disease

    SciTech Connect

    Ratliff, N.B.

    1985-04-01

    Lesions of the extrarenal arteries which are associated with hypertension are described. Included are descriptions of the development, stages, and complications of atherosclerotic plaques; intimal fibroplasia and the medial fibromuscular dysplasias; Takayasu's aortitis; radiation injury; and a newly described arterial disease, medial agenesis. Also described is the development of atherosclerosis in saphenous vein bypass grafts and the effects of transluminal angioplasty. 28 references.

  16. Cerebral cavernous malformation (CCM) disease: from monogenic forms to genetic susceptibility factors.

    PubMed

    Trapani, E; Retta, S F

    2015-09-01

    Cerebral cavernous malformation (CCM) is a vascular disease of proven genetic origin, which may arise sporadically or can be inherited as autosomal dominant condition with incomplete penetrance and highly variable expressivity. CCM lesions manifest across a range of different phenotypes, including wide interindividual differences in lesion number, size and susceptibility to intracerebral hemorrhage (ICH), and may remain asymptomatic during the host's lifetime or result in pathological conditions of various type and severity at any age, with symptoms ranging from relatively minor (but still disabling) headaches through to very severe neurological deficits, seizures, and stroke. Currently, surgical removal of accessible lesions is the only direct therapeutic approach for CCM disease. However, whereas little information is available on the natural history of risk for patients to develop serious complications, such as ICH, prognostic biomarkers remain to be identified in order to ensure timely and optimal clinical decision making. In recent years, it has become clear that the three known CCM genes play an important role in controlling signalling pathways involved in cell responses to oxidative stress, pointing to a novel pathogenic mechanism whereby the function of CCM genes may be relevant in preventing vascular dysfunctions triggered by oxidative stress events. In turn, these novel findings have raised the possibility that genetic susceptibility factors related to differences in sensitivity to oxidative stress, including genetic polymorphisms, may contribute to interindividual differences in CCM disease susceptibility and severity. This review discusses recent progress toward the understanding of molecular mechanisms of pathogenesis and the identification of genetic susceptibility factors that could influence onset, progression and clinical severity of CCM disease, as well as consequent implications for the development of novel, safe and effective therapeutic

  17. Cancer linked to Alzheimer disease but not vascular dementia

    PubMed Central

    Roe, C M.; Fitzpatrick, A L.; Xiong, C; Sieh, W; Kuller, L; Miller, J P.; Williams, M M.; Kopan, R; Behrens, M I.; Morris, J C.

    2010-01-01

    Objective: To investigate whether cancer is associated with Alzheimer disease (AD) and vascular dementia (VaD). Methods: Cox proportional hazards models were used to test associations between prevalent dementia and risk of future cancer hospitalization, and associations between prevalent cancer and risk of subsequent dementia. Participants in the Cardiovascular Health Study–Cognition Substudy, a prospective cohort study, aged 65 years or older (n = 3,020) were followed a mean of 5.4 years for dementia and 8.3 years for cancer. Results: The presence of any AD (pure AD + mixed AD/VaD; hazard ratio [HR] = 0.41, 95% confidence interval [CI] = 0.20–0.84) and pure AD (HR = 0.31, 95% CI = 0.12–0.86) was associated with a reduced risk of future cancer hospitalization, adjusted for demographic factors, smoking, obesity, and physical activity. No significant associations were found between dementia at baseline and rate of cancer hospitalizations for participants with diagnoses of VaD. Prevalent cancer was associated with reduced risk of any AD (HR = 0.72; 95% CI = 0.52–0.997) and pure AD (HR = 0.57; 95% CI = 0.36–0.90) among white subjects after adjustment for demographics, number of APOE ε4 alleles, hypertension, diabetes, and coronary heart disease; the opposite association was found among minorities, but the sample size was too small to provide stable estimates. No significant association was found between cancer and subsequent development of VaD. Conclusions: In white older adults, prevalent Alzheimer disease (AD) was longitudinally associated with a reduced risk of cancer, and a history of cancer was associated with a reduced risk of AD. Together with other work showing associations between cancer and Parkinson disease, these findings suggest the possibility that cancer is linked to neurodegeneration. GLOSSARY 3MSE = modified Mini-Mental State Examination; AD = Alzheimer disease; ADDTC = Alzheimer Disease Diagnostic and Treatment Centers; CHD = coronary heart

  18. Prevention and Management of Cerebral Small Vessel Disease

    PubMed Central

    Mok, Vincent

    2015-01-01

    Lacunar infarcts/lacunes, white matter hyperintensities (WMH), and cerebral microbleeds (CMBs) are considered various manifestations of cerebral small vessel disease (SVD). Since the exact mechanisms of these manifestations differ, their associated risk factors differ. High blood pressure is the most consistent risk factor for all of these manifestations. However, a "J curve" phenomenon in terms of blood pressure probably exists for WMH. The association between cholesterol levels and lacunar infarcts/lacunes or WMH was less consistent and sometimes conflicting; a low cholesterol level probably increases the risk of CMBs. Homocysteinemia appears to be associated with WMH. It is noteworthy that the risk factors profile may also differ between different lacunar patterns and CMBs located at different parts of the brain. Thrombolysis, antihypertensives, and statins are used to treat patients with symptomatic lacunar infarction, just as in those with other stroke subtypes. However, it should be remembered that bleeding risks increase in patients with extensive WMH and CMBs after thrombolysis therapy. According to the Secondary Prevention of Small Subcortical Strokes trial results, a blood pressure reduction to <130 mmHg is recommended in patients with symptomatic lacunar infarction. However, an excessive blood pressure decrease may induce cognitive decline in older patients with extensive WMH. Dual antiplatelet therapy (aspirin plus clopidogrel) should be avoided because of the excessive risk of intracerebral hemorrhage. Although no particular antiplatelet is recommended, drugs such as cilostazol or triflusal may have advantages for patients with SVD since they are associated with less frequent bleeding complications than aspirin. PMID:26060798

  19. Role of cerebral cortex in the neuropathology of Huntington's disease

    PubMed Central

    Estrada-Sánchez, Ana M.; Rebec, George V.

    2013-01-01

    An expansion of glutamine repeats in the N-terminal domain of the huntingtin protein leads to Huntington's disease (HD), a neurodegenerative condition characterized by the presence of involuntary movements, dementia, and psychiatric disturbances. Evaluation of postmortem HD tissue indicates that the most prominent cell loss occurs in cerebral cortex and striatum, forebrain regions in which cortical pyramidal neurons (CPNs) and striatal medium spiny neurons (MSNs) are the most affected. Subsequent evidence obtained from HD patients and especially from transgenic mouse models of HD indicates that long before neuronal death, patterns of communication between CPNs and MSNs become dysfunctional. In fact, electrophysiological signaling in transgenic HD mice is altered even before the appearance of the HD behavioral phenotype, suggesting that dysfunctional cortical input to the striatum sets the stage for the emergence of HD neurological signs. Striatal MSNs, moreover, project back to cortex via multi-synaptic connections, allowing for even further disruptions in cortical processing. An effective therapeutic strategy for HD, therefore, may lie in understanding the synaptic mechanisms by which it dysregulates the corticostriatal system. Here, we review literature evaluating the molecular, morphological, and physiological alterations in the cerebral cortex, a key component of brain circuitry controlling motor behavior, as they occur in both patients and transgenic HD models. PMID:23423362

  20. Spatial mapping of dynamic cerebral autoregulation by multichannel near-infrared spectroscopy in high-grade carotid artery disease

    NASA Astrophysics Data System (ADS)

    Reinhard, Matthias; Schumacher, F. Konrad; Rutsch, Sebastian; Oeinck, Maximilian; Timmer, Jens; Mader, Irina; Schelter, Björn; Weiller, Cornelius; Kaller, Christoph P.

    2014-09-01

    The exact spatial distribution of impaired cerebral autoregulation in carotid artery disease is unknown. In this pilot study, we present a new approach of multichannel near-infrared spectroscopy (mcNIRS) for noninvasive spatial mapping of dynamic autoregulation in carotid artery disease. In 15 patients with unilateral severe carotid artery stenosis or occlusion, cortical hemodynamics in the bilateral frontal cortex were assessed from changes in oxyhemoglobin concentration using 52-channel NIRS (spatial resolution ˜2 cm). Dynamic autoregulation was graded by the phase shift between respiratory-induced 0.1 Hz oscillations of blood pressure and oxyhemoglobin. Ten of 15 patients showed regular phase values in the expected (patho) physiological range. Five patients had clearly outlying irregular phase values mostly due to artifacts. In patients with a regular phase pattern, a significant side-to-side difference of dynamic autoregulation was observed for the cortical border zone area between the middle and anterior cerebral artery (p<0.05). In conclusion, dynamic cerebral autoregulation can be spatially assessed from slow hemodynamic oscillations with mcNIRS. In high-grade carotid artery disease, cortical dynamic autoregulation is affected mostly in the vascular border zone. Spatial mapping of dynamic autoregulation may serve as a powerful tool for identifying brain regions at specific risks for hemodynamic infarction.

  1. Non-atherosclerotic vascular disease in the young.

    PubMed

    Camilo, Osvaldo; Goldstein, Larry B

    2005-10-01

    There are a large variety of non-atherosclerotic causes of ischemic stroke in the young. Arterial dissection, most commonly associated with non-traumatic causes, is among the most common. Both the carotid and vertebrobasilar circulations can be affected. The vasculitidies represent a rare, but potentially treatable series of conditions that can lead to stroke through diverse mechanisms. Moyamoya is a nonatherosclerotic, noninflammatory, nonamyloid vasculopathy characterized by chronic progressive stenosis or occlusion of the distal internal carotid arteries and/or proximal portions of the middle and/or anterior cerebral arteries. Moyamoya can be idiopathic (moyamoya disease) or the result of other conditions. An appreciation of the unusual causes of stroke in the young is important when considering secondary prevention measures.

  2. A vascular endothelial growth factor deficiency characterises scleroderma lung disease.

    PubMed

    De Santis, Maria; Bosello, Silvia Laura; Capoluongo, Ettore; Inzitari, Rosanna; Peluso, Giusy; Lulli, Paola; Zizzo, Gaetano; Bocci, Mario; Tolusso, Barbara; Zuppi, Cecilia; Castagnola, Massimo; Ferraccioli, Gianfranco

    2012-09-01

    Vascular endothelial growth factor (VEGF) is thought to play an important role in systemic sclerosis (SSc) pathogenesis. It was found to be upregulated in the serum and in the affected skin of scleroderma patients. However, its involvement in scleroderma lung disease is not clear. This study aimed to evaluate VEGF concentration in the bronchoalveolar lavage fluid (BALF) of scleroderma patients with interstitial lung disease, to correlate the cytokine levels in plasma and in the lung with pulmonary functional, radiological and cellular parameters, and with the progression of lung disease. BALF and plasma VEGF concentrations were analysed by ELISA in 55 SSc patients with lung disease and 17 controls. Cytokine real-time PCR messenger RNA expression in alveolar macrophages was assessed. Lung involvement progression was evaluated after a 1-year follow-up. VEGF was found to be significantly lower in the BALF of scleroderma patients compared with controls. The lowest concentrations were observed in SSc patients with alveolitis. A decreased VEGF expression in alveolar macrophages was found in SSc patients with alveolitis. VEGF concentration in BALF correlated inversely with the ground glass score on high-resolution CT and with BALF neutrophil cell count. Moreover, SSc patients with a lower VEGF concentration showed a worsening in the interstitial score at follow-up. Scleroderma interstitial lung disease is characterised by a VEGF deficiency. Lower concentrations were found in patients with progression of lung disease.

  3. Inflammasomes link vascular disease with neuroinflammation and brain disorders.

    PubMed

    Lénárt, Nikolett; Brough, David; Dénes, Ádám

    2016-10-01

    The role of inflammation in neurological disorders is increasingly recognised. Inflammatory processes are associated with the aetiology and clinical progression of migraine, psychiatric conditions, epilepsy, cerebrovascular diseases, dementia and neurodegeneration, such as seen in Alzheimer's or Parkinson's disease. Both central and systemic inflammatory actions have been linked with the development of brain diseases, suggesting that complex neuro-immune interactions could contribute to pathological changes in the brain across multiple temporal and spatial scales. However, the mechanisms through which inflammation impacts on neurological disease are improperly defined. To develop effective therapeutic approaches, it is imperative to understand how detrimental inflammatory processes could be blocked selectively, or controlled for prolonged periods, without compromising essential immune defence mechanisms. Increasing evidence indicates that common risk factors for brain disorders, such as atherosclerosis, diabetes, hypertension, obesity or infection involve the activation of NLRP3, NLRP1, NLRC4 or AIM2 inflammasomes, which are also associated with various neurological diseases. This review focuses on the mechanisms whereby inflammasomes, which integrate diverse inflammatory signals in response to pathogen-driven stimuli, tissue injury or metabolic alterations in multiple cell types and different organs of the body, could functionally link vascular- and neurological diseases and hence represent a promising therapeutic target.

  4. Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease.

    PubMed

    Lincoff, A Michael; Nicholls, Stephen J; Riesmeyer, Jeffrey S; Barter, Philip J; Brewer, H Bryan; Fox, Keith A A; Gibson, C Michael; Granger, Christopher; Menon, Venu; Montalescot, Gilles; Rader, Daniel; Tall, Alan R; McErlean, Ellen; Wolski, Kathy; Ruotolo, Giacomo; Vangerow, Burkhard; Weerakkody, Govinda; Goodman, Shaun G; Conde, Diego; McGuire, Darren K; Nicolau, Jose C; Leiva-Pons, Jose L; Pesant, Yves; Li, Weimin; Kandath, David; Kouz, Simon; Tahirkheli, Naeem; Mason, Denise; Nissen, Steven E

    2017-05-18

    The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of

  5. Antiphospholipid Syndrome and Vascular Ischemic (Occlusive) Diseases: An Overview

    PubMed Central

    2007-01-01

    Antiphospholipid syndrome (APS) is primarily considered to be an autoimmune pathological condition that is also referred to as "Hughes syndrome". It is characterized by arterial and/or venous thrombosis and pregnancy pathologies in the presence of anticardiolipin antibodies and/or lupus anticoagulant. APS can occur either as a primary disease or secondary to a connective tissue disorder, most frequently systemic lupus erythematosus (SLE). Damage to the nervous system is one of the most prominent clinical constellations of sequelae in APS and includes (i) arterial/venous thrombotic events, (ii) psychiatric features and (iii) other non-thrombotic neurological syndromes. In this overview we compare the most important vascular ischemic (occlusive) disturbances (VIOD) with neuro-psychiatric symptomatics, together with complete, updated classifications and hypotheses for the etio-pathogenesis of APS with underlying clinical and laboratory criteria for optimal diagnosis and disease management. PMID:18159581

  6. The development of cardiovascular and cerebral vascular control in preterm infants.

    PubMed

    Fyfe, Karinna L; Yiallourou, Stephanie R; Wong, Flora Y; Horne, Rosemary S C

    2014-08-01

    Over the past three decades there has been a steady increase in the incidence of preterm birth. The worldwide rate of preterm birth is estimated to be 9.6% of all births, a total of almost 13 million births annually. Preterm birth is associated with a range of adverse cardiovascular and central nervous system outcomes, which may be attributed to altered development of these systems following preterm birth. Preterm birth has a considerable impact on cardiovascular parameters with preterm infants displaying higher heart rates and reduced blood pressure when compared to term born infants at matched ages. Furthermore, premature infants have altered autonomic control of cardiovascular parameters which manifests as abnormalities in heart rate variability and baroreflex mediated control of heart rate and blood pressure. As a result, systemic cardiovascular parameters can be unstable following preterm birth which may place stress on the neonatal brain. The brain of a preterm infant is particularly vulnerable to these fluctuations due to immature cerebral haemodynamics. Preterm infants, particularly those who are very preterm or unwell, display fluctuating pressure-passivity between systemic blood pressure and cerebral blood flow representing a considerably increased risk of cerebral haemorrhage or hypoxia. This is further compounded by immaturity of cerebral blood flow-metabolism coupling, which means increased metabolic demand cannot adequately be met by increased cerebral blood flow. It has been suggested that adverse long-term outcomes following preterm birth may occur as a result of exposure to physiological stress either in-utero or early in infancy. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  7. Fluid-Attenuated Inversion Recovery Vascular Hyperintensity Topography, Novel Imaging Marker for Revascularization in Middle Cerebral Artery Occlusion.

    PubMed

    Liu, Dezhi; Scalzo, Fabien; Rao, Neal M; Hinman, Jason D; Kim, Doojin; Ali, Latisha K; Saver, Jeffrey L; Sun, Wen; Dai, Qiliang; Liu, Xinfeng; Liebeskind, David S

    2016-11-01

    In acute arterial occlusion, fluid-attenuated inversion recovery vascular hyperintensity (FVH) has been linked to slow flow in leptomeningeal collaterals and cerebral hypoperfusion, but the impact on clinical outcome is still controversial. In this study, we aimed to investigate the association between FVH topography or FVH-Alberta Stroke Program Early CT Score (ASPECTS) pattern and outcome in acute M1-middle cerebral artery occlusion patients with endovascular treatment. We included acute M1-middle cerebral artery occlusion patients treated with endovascular therapy (ET). All patients had diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery before ET. Distal FVH-ASPECTS was evaluated according to distal middle cerebral artery-ASPECT area (M1-M6) and acute DWI lesion was also reviewed. The presence of FVH inside and outside DWI-positive lesions was separately analyzed. Clinical outcome after ET was analyzed with respect to different distal FVH-ASPECTS topography. Among 101 patients who met inclusion criteria for the study, mean age was 66.2±17.8 years and median National Institutes of Health Stroke Scale was 17.0 (interquartile range, 12.0-21.0). FVH-ASPECTS measured outside of the DWI lesion was significantly higher in patients with good outcome (modified Rankin Scale [mRS] score of 0-2; 8.0 versus 4.0, P<0.001). Logistic regression demonstrated that FVH-ASPECTS outside of the DWI lesion was independently associated with clinical outcome of these patients (odds ratio, 1.3; 95% confidence interval, 1.06-1.68; P=0.013). FVH-ASPECTS inside the DWI lesion was associated with hemorrhagic transformation (odds ratio, 1.3; 95% confidence interval, 1.04-1.51; P=0.019). Higher FVH-ASPECTS measured outside the DWI lesion is associated with good clinical outcomes in patients undergoing ET. FVH-ASPECTS measured inside the DWI lesion was predictive of hemorrhagic transformation. The FVH pattern, not number, can serve as an imaging selection marker for ET in

  8. Cerebrolysin improves symptoms and delays progression in patients with Alzheimer's disease and vascular dementia.

    PubMed

    Allegri, R F; Guekht, A

    2012-04-01

    Dementia is the result of various cerebral disorders, leading to an acquired loss of memory and impaired cognitive ability. The most common forms are Alzheimer's disease (AD) and vascular dementia (VaD). Neurotrophic factors are essential for the survival and differentiation of developing neurons and protecting them against damage under pathologic conditions. Cerebrolysin is a peptide preparation that mimics the pleiotropic effects of neurotrophic factors. Several clinical trials investigating the therapeutic efficacy of Cerebrolysin in AD and VaD have confirmed the proof of concept. The results of these trials have shown statistically significant and clinically relevant treatment effects of Cerebrolysin on cognitive, global and functional domains in mild to moderately severe stages of dementia. Doses of 10 and 30 mL were the most effective, but higher doses of up to 60 mL turned out to be most effective in improving neuropsychiatric symptoms, which become relevant at later stages of the disease. Combining treatment with cholinesterase inhibitors and Cerebrolysin indicated long-term synergistic treatment effects in mild to moderate AD. The efficacy of Cerebrolysin persisted for up to several months after treatment suggesting Cerebrolysin has not merely symptomatic benefits, but a disease-delaying potential. This paper reviews the clinical efficacy of Cerebrolysin in the treatment of dementia. Data were obtained from international, multicenter, randomized clinical trials performed in compliance with Good Clinical Practice and the principles of the Declaration of Helsinki (1964) and subsequent revisions.

  9. Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin.

    PubMed

    Retta, Saverio Francesco; Glading, Angela J

    2016-12-01

    Cerebral Cavernous Malformation (CCM) is a vascular disease of proven genetic origin, which may arise sporadically or is inherited as an autosomal dominant condition with incomplete penetrance and highly variable expressivity. CCM lesions exhibit a range of different phenotypes, including wide inter-individual differences in lesion number, size, and susceptibility to intracerebral hemorrhage (ICH). Lesions may remain asymptomatic or result in pathological conditions of various type and severity at any age, with symptoms ranging from recurrent headaches to severe neurological deficits, seizures, and stroke. To date there are no direct therapeutic approaches for CCM disease besides the surgical removal of accessible lesions. Novel pharmacological strategies are particularly needed to limit disease progression and severity and prevent de novo formation of CCM lesions in susceptible individuals. Useful insights into innovative approaches for CCM disease prevention and treatment are emerging from a growing understanding of the biological functions of the three known CCM proteins, CCM1/KRIT1, CCM2 and CCM3/PDCD10. In particular, accumulating evidence indicates that these proteins play major roles in distinct signaling pathways, including those involved in cellular responses to oxidative stress, inflammation and angiogenesis, pointing to pathophysiological mechanisms whereby the function of CCM proteins may be relevant in preventing vascular dysfunctions triggered by these events. Indeed, emerging findings demonstrate that the pleiotropic roles of CCM proteins reflect their critical capacity to modulate the fine-tuned crosstalk between redox signaling and autophagy that govern cell homeostasis and stress responses, providing a novel mechanistic scenario that reconciles both the multiple signaling pathways linked to CCM proteins and the distinct therapeutic approaches proposed so far. In addition, recent studies in CCM patient cohorts suggest that genetic susceptibility

  10. Molecular Pathogenesis of Retinal and Choroidal Vascular Diseases

    PubMed Central

    Campochiaro, Peter A.

    2015-01-01

    There are two major types of ocular neovascularization that affect the retina, retinal neovascularization (NV) and subretinal or choroidal NV. Retinal NV occurs in a group of diseases referred to as ischemic retinopathies in which damage to retinal vessels results in retinal ischemia. Most prevalent of these are diabetic retinopathy and retinal vein occlusions. Subretinal and choroidal NV occur in diseases of the outer retina and Bruch’s membrane, the most prevalent of which is age-related macular degeneration. Numerous studies in mouse models have helped to elucidate the molecular pathogenesis underlying retinal, subretinal, and choroidal NV. There is considerable overlap because the precipitating event in each is stabilization of hypoxia inducible factor-1 (HIF-1) which leads to upregulation of several hypoxia-regulated gene products, including vascular endothelial growth factor (VEGF), angiopoietin 2, vascular endothelial-protein tyrosine phosphatase (VE-PTP), and several others. Stimulation of VEGF signaling and suppression of Tie2 by angiopoietin 2 and VE-PTP are critical for sprouting of retinal, subretinal, and choroidal NV, with perturbation of Bruch’s membrane also needed for the latter. Additional HIF-1-regulated gene products cause further stimulation of the NV. It is difficult to model macular edema in animals and therefore proof-of-concept clinical trials were done and demonstrated that VEGF plays a central role and that suppression of Tie2 is also important. Neutralization of VEGF is currently the first line therapy for all of the above disease processes, but new treatments directed at some of the other molecular targets, particularly stabilization of Tie2, are likely to provide additional benefit for subretinal/choroidal NV and macular edema. In addition, the chronicity of these diseases as well as the implication of VEGF as a cause of retinal nonperfusion and progression of background diabetic retinopathy make sustained delivery approaches for

  11. Impaired vascular remodeling after endothelial progenitor cell transplantation in MMP9-deficient mice suffering cortical cerebral ischemia

    PubMed Central

    Morancho, Anna; Ma, Feifei; Barceló, Verónica; Giralt, Dolors; Montaner, Joan; Rosell, Anna

    2015-01-01

    Endothelial progenitor cells (EPCs) are being investigated for advanced therapies, and matrix metalloproteinase 9 (MMP9) has an important role in stroke recovery. Our aim was to determine whether tissue MMP9 influences the EPC-induced angiogenesis after ischemia. Wild-type (WT) and MMP9-deficient mice (MMP9/KO) were subjected to cerebral ischemia and treated with vehicle or outgrowth EPCs. After 3 weeks, we observed an increase in the peri-infarct vessel density in WT animals but not in MMP9/KO mice; no differences were found in the vehicle-treated groups. Our data suggest that tissue MMP9 has a crucial role in EPC-induced vascular remodeling after stroke. PMID:26219597

  12. SPECT study of regional cerebral blood flow in Alzheimer disease

    SciTech Connect

    Bonte, F.J.; Ross, E.D.; Chehabi, H.H.; Devous, M.D. Sr.

    1986-07-01

    A common cause of dementia in late midlife and old age is Alzheimer disease (AD), which affects more than one in 20 individuals over the age of 65. Past studies of regional cerebral blood flow (rCBF) in patients with AD here suggested blood flow abnormalities, but findings have differed. We have studied 37 patients diagnosed as having AD with inhalation and washout of /sup 133/Xe and single-photon emission computed tomography (SPECT), obtaining evidence of abnormal rCBF patterns in 19. Flow reductions were most common in the temporoparietal regions and were occasionally found in the frontal areas. Investigators using positron-emission tomography (PET) have identified similar findings with respect to rCBF and regional oxygen, glucose, and protein metabolism. The SPECT determination of rCBF, which gives information similar to that provided by PET, may assume importance in the diagnosis of AD and in the differential diagnosis of the dementias.

  13. Vascular structure and binomial statistics for response modeling in radiosurgery of cerebral arteriovenous malformations

    NASA Astrophysics Data System (ADS)

    Andisheh, Bahram; Bitaraf, Mohammad A.; Mavroidis, Panayiotis; Brahme, Anders; Lind, Bengt K.

    2010-04-01

    Radiation treatment of arteriovenous malformations (AVMs) has a slow and progressive vaso-occlusive effect. Some studies suggested the possible role of vascular structure in this process. A detailed biomathematical model has been used, where the morphological, biophysical and hemodynamic characteristics of intracranial AVM vessels are faithfully reproduced. The effect of radiation on plexiform and fistulous AVM nidus vessels was simulated using this theoretical model. The similarities between vascular and electrical networks were used to construct this biomathematical AVM model and provide an accurate rendering of transnidal and intranidal hemodynamics. The response of different vessels to radiation and their obliteration probability as a function of different angiostructures were simulated and total obliteration was defined as the probability of obliteration of all possible vascular pathways. The dose response of the whole AVM is observed to depend on the vascular structure of the intra-nidus AVM. Furthermore, a plexiform AVM appears to be more prone to obliteration compared with an AVM of the same size but having more arteriovenous fistulas. Finally, a binomial model was introduced, which considers the number of crucial vessels and is able to predict the dose response behavior of AVMs with a complex vascular structure.

  14. Cerebral Small Vessel Disease: Targeting Oxidative Stress as a Novel Therapeutic Strategy?

    PubMed Central

    De Silva, T. Michael; Miller, Alyson A.

    2016-01-01

    Cerebral small vessel disease (SVD) is a major contributor to stroke, and a leading cause of cognitive impairment and dementia. Despite the devastating effects of cerebral SVD, the pathogenesis of cerebral SVD is still not completely understood. Moreover, there are no specific pharmacological strategies for its prevention or treatment. Cerebral SVD is characterized by marked functional and structural abnormalities of the cerebral microcirculation. The clinical manifestations of these pathological changes include lacunar infarcts, white matter hyperintensities, and cerebral microbleeds. The main purpose of this review is to discuss evidence implicating oxidative stress in the arteriopathy of both non-amyloid and amyloid (cerebral amyloid angiopathy) forms of cerebral SVD and its most important risk factors (hypertension and aging), as well as its contribution to cerebral SVD-related brain injury and cognitive impairment. We also highlight current evidence of the involvement of the NADPH oxidases in the development of oxidative stress, enzymes that are a major source of reactive oxygen species in the cerebral vasculature. Lastly, we discuss potential pharmacological strategies for oxidative stress in cerebral SVD, including some of the historical and emerging NADPH oxidase inhibitors. PMID:27014073

  15. Cerebro vascular reactivity (CVR) of middle cerebral artery in response to CO2 5% inhalation in preeclamptic women.

    PubMed

    Sariri, Elaheh; Vahdat, Mansoureh; Behbahani, Afsaneh Shariati; Rohani, Mohammad; Kashanian, Maryam

    2013-07-01

    To compare the cerebro vascular reactivity (CVR) of middle cerebral artery (MCA) in response to CO2 5% inhalation between preeclamptic and normotensive pregnant women, also, between mild and severe preeclampsia. A comparative study was performed on 61 women with preeclampsia and 65 normotensive pregnant women who were in the third trimester of gestation. MCA transcranial Doppler ultrasound was used to measure CVR in response to CO2 5% inhalation. Pulsatility index (PI), resistance index (RI), blood pressure, maternal age, gestational age and gravidity were also recorded. Baseline PI and RI were lower in the preeclamptic group (p < 0.05). Inhalation of CO2 5% caused significant increase in CVR among normotensive pregnant women in comparison with preeclamptic group (1.006 ± 0.229 versus 0.503 ± 0.209, p = 0.0001). Significantly, more cerebral vasodilatation was found among mild preeclamptic women in comparison with severe preeclamptic women (0.583 ± 0.193 versus 0.383 ± 0.173, p = 0.0001). The receiver operating characteristics curve analysis revealed acceptable difference between CO2 stimulation test of preeclamptic and normotensive women (Area under curve = 0.973, p = 0.0001). CVR in response to CO2 5% is less in preeclamptic pregnant women than normotensives, also, in severe preeclampsia, it is less than mild preeclampsia.

  16. Cerebral Small Vessel Disease Burden Is Increased in Systemic Lupus Erythematosus

    PubMed Central

    Wiseman, Stewart J.; Bastin, Mark E.; Jardine, Charlotte L.; Barclay, Gayle; Hamilton, Iona F.; Sandeman, Elaine; Hunt, David; Amft, E. Nicole; Thomson, Susan; Belch, Jill F.F.; Ralston, Stuart H.

    2016-01-01

    Background and Purpose— Systemic lupus erythematosus (SLE) increases stroke risk, but the mechanism is uncertain. This study aimed to determine the association between SLE and features on neuroimaging of cerebral small vessel disease (SVD), a risk factor for stroke. Methods— Consecutive patients attending a clinic for SLE were recruited. All patients underwent brain magnetic resonance imaging; had blood samples taken for markers of inflammation, endothelial dysfunction, cholesterol, and autoantibodies; and underwent cognitive and psychiatric testing. The data were compared with sex- and age-matched healthy controls and patients with minor stroke. Features of SVD were measured, a total SVD score calculated, and associations sought with vascular risk factors, cognition, SLE activity, and disease duration. Results— Fifty-one SLE patients (age: 48.8 years; SD: 14.3 years) had a greater total SVD score compared with healthy controls (1 versus 0; P<0.0001) and stroke patients (1 versus 0; P=0.02). There were higher perivascular spaces and deep white matter hyperintensity scores and more superficial brain atrophy in SLE patients versus healthy controls. Despite fewer vascular risk factors than similarly aged stroke patients, SLE patients had similar or more of some SVD features. The total SVD score was not associated with SLE activity, cognition, disease duration, or any blood measure. Conclusions— In this data set, SLE patients had a high burden of SVD features on magnetic resonance imaging, particularly perivascular spaces. A larger longitudinal study is warranted to determine the causes of SVD features in SLE and clinical implications. PMID:27703087

  17. Vascular calcification in chronic kidney disease: Pathogenesis and clinical implication

    PubMed Central

    Disthabanchong, Sinee

    2012-01-01

    Cardiovascular disease is the leading cause of death among patients with chronic kidney disease (CKD). Vascular calcification (VC) is one of the independent risk factors associated with cardiovascular disease and cardiovascular mortality in both the general population and CKD patients. Earlier evidence revealed substantially higher prevalence of VC in young adults on chronic hemodialysis compared to the general population in the same age range, indicating the influence of CKD-related risk factors on the development of VC. Pathogenesis of VC involves an active, highly organized cellular transformation of vascular smooth muscle cells to bone forming cells evidenced by the presence of bone matrix proteins in the calcified arterial wall. VC occurs in both the intima and the media of arterial wall with medial calcification being more prevalent in CKD. In addition to traditional cardiovascular risks, risk factors specific to CKD such as phosphate retention, excess of calcium, history of dialysis, active vitamin D therapy in high doses and deficiency of calcification inhibitors play important roles in promoting the development of VC. Non-contrast multi-slice computed tomography has often been used to detect coronary artery calcification. Simple plain radiographs of the lateral lumbar spine and pelvis can also detect VC in the abdominal aorta and femoral and iliac arteries. Currently, there is no specific therapy to reverse VC. Reduction of calcium load, lowering phosphate retention using non-calcium containing phosphate binders, and moderate doses of active vitamin D may attenuate progression. Parenteral sodium thiosulfate has also been shown to delay VC progression. PMID:24175241

  18. Prevalence and impact of vascular and Alzheimer pathologies in Lewy body disease.

    PubMed

    Jellinger, Kurt A; Attems, Johannes

    2008-04-01

    Whereas the prevalence and impact of vascular pathology in Alzheimer diease (AD) are well established, the role of vascular and Alzheimer pathologies in the progression of neurodegeneration and cognitive impairment in Parkinson disease (PD) is under discussion. A retrospective clinico-pathologic study of 100 patients with autopsy proven PD (including 44 cases with dementia/PDD) and 20 cases of dementia with Lewy bodies (DLB) confirmed essential clinical (duration of illness, Mini-Mental State Examination/MMSE, age at death) and morphologic differences between these groups; Lewy body Braak scores and Alzheimer pathologies (neuritic Braak stage, cortical Abeta plaque load, and generalized cerebral amyloid angiopathy or CAA) were significantly higher/more severe in DLB and PDD than in PD without dementia. Duration of illness showed no association to any of the examined pathologic parameters, while there was a moderate association between LB scores and neuritic Braak stages, the latter significantly increasing with age. Significant association between cerebrovascular lesions and neuritic Braak stage was seen in PDD but not in PD subjects without dementia. These data suggest an influence of Alzheimer-related lesions on the progression of the neurodegenerative process and, in particular, on cognitive decline in both PDD and DLB. On the other hand, both these factors in PD and DLB appear to be largely independent from coexistent vascular pathology, except in cases with severe cerebrovascular lesions or those related to neuritic AD pathology. Assessment of ApoE genotype in a small number of cases showed no significant differences in the severity of Abeta plaque load and CAA except for much lower intensities in non-demented epsilon3/3 patients. Despite increasing evidence suggesting synergistic reactions between alpha-synuclein (alphaSyn), tau and Abeta-peptides, the major protein markers of both AD and Lewy body diseases, and of both vascular pathology and AD, the

  19. Optical spectroscopy and prevention of deleterious cerebral vascular effects of ethanol by magnesium ions.

    PubMed

    Barbour, Randall L; Gebrewold, Asefa; Altura, Bella T; Altura, Burton M

    2002-06-28

    Previously, it has been suggested that acute ethanol (alcohol) administration can result in concentration-dependent vasoconstriction and decreased cerebral blood flow. Here, we present in vivo results using rapid (240 nm/min) optical backscatter measurements, with an intact cranial preparation in the rat, indicating that acute infusion of ethanol directly into the rat brain rapidly produces dose-dependent vasoconstriction of the cerebral microcirculation associated with a pronounced reduction in tissue blood content, pronounced rises in deoxyhemoglobin, significantly increased levels of reduced cytochrome oxidase and microvascular damage as the dose increases. Furthermore, we present in vivo experiments demonstrating the capability of magnesium ions (Mg(2+)) to attenuate and prevent these deleterious responses. Optical backscatter spectra (500-800 nm) were obtained by directing a single sending and receiving fiber to a portion of the left parietal cranium (in anesthetized rats), shaved to a translucent appearance to facilitate optical penetration. In the absence of added Mg(2+), infusion of a 10% solution of ethanol at 0.34 ml/min ( approximately 26.8 mg/min) produced prompt vasoconstriction as evidenced by a greater than 90% loss of oxyhemoglobin from the field-of-view and increases in levels of reduced cytochrome oxidase to between 50% and >90%. These effects were partially, to nearly completely, attenuated by the addition of MgCl(2) to the infusate containing added ethanol. Of special interest was the observation that attenuation of the vasoconstrictive effect of ethanol by Mg(2+) persisted despite a subsequent ethanol challenge without added Mg(2+). The results obtained demonstrate that, depending on dose, ethanol can produce prompt and severe vasoconstriction of the intact cerebral microcirculation and that infusion of moderate doses of Mg(2+) can largely attenuate and prevent this response. We conclude that appreciable, graded changes in cerebral cytochrome

  20. Diffuse correlation spectroscopy for non-invasive, micro-vascular cerebral blood flow measurement

    PubMed Central

    Durduran, Turgut; Yodh, Arjun G.

    2013-01-01

    Diffuse correlation spectroscopy (DCS) uses the temporal fluctuations of near-infrared (NIR) light to measure cerebral blood flow (CBF) non-invasively. Here, we provide a brief history of DCS applications in brain with an emphasis on the underlying physical ideas, common instrumentation and validation. Then we describe recent clinical research that employs DCS-measured CBF as a biomarker of patient well-being, and as an indicator of hemodynamic and metabolic response to functional stimuli. PMID:23770408

  1. [The vascular manifestations of Behçet's disease: a case report].

    PubMed

    Basaran, M; Sever, K; Kafali, E; Ugurlucan, M; Alpagut, U; Dayioglu, E

    2005-03-01

    Behçet's disease is an inflammatory vasculitis which affects the arteries and veins. The vascular pathologies are the rare complications of this disease. We present here a patient with Behçet's disease who has been hospitalized several times because of plurifocal vascular manifestations.

  2. Dietary vitamin K and therapeutic warfarin alter susceptibility to vascular calcification in experimental chronic kidney disease

    USDA-ARS?s Scientific Manuscript database

    The leading cause of death in patients with chronic kidney disease (CKD) is cardiovascular disease (CVD), with vascular calcification (VC) being a key modifier of disease progression. A local regulator of vascular calcification is vitamin K. This gamma-glutamyl carboxylase substrate is an essential ...

  3. Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease.

    PubMed

    Bowman, Louise; Hopewell, Jemma C; Chen, Fang; Wallendszus, Karl; Stevens, William; Collins, Rory; Wiviott, Stephen D; Cannon, Christopher P; Braunwald, Eugene; Sammons, Emily; Landray, Martin J

    2017-09-28

    Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. Among

  4. Posterior Cerebral Artery Insufficiency in Pediatric Moyamoya Disease

    PubMed Central

    Lee, Ji Yeoun; Kim, Seung-Ki; Phi, Ji Hoon

    2015-01-01

    The majority of clinical studies on moyamoya disease (MMD) have focused on anterior circulation. The disease involvement of posterior circulation in MMD, mainly in the posterior cerebral artery (PCA), has been mentioned since the early 1980s, and it has been repeatedly emphasized as one of the most important factors related to poor prognosis in MMD. However, its clinical features and outcome have only been elucidated during the last few years. In this review, the angiographic definition of PCA stenosis is summarized. The clinical features are elucidated as being either early-onset or delayed-onset, according to the time of PCA stenosis diagnosis in reference to the anterior circulation revascularization surgeries. The surgical strategy and hypothesis on the mechanism of PCA stenosis is also briefly mentioned. It appears that some MMD patients may show PCA stenosis during the early or late course of the disease and that the presenting symptoms may vary. Because the hemodynamic compromise caused by PCA stenosis may respond well to surgical treatment, clinicians should be aware of the condition, especially during follow-up of MMD patients. PMID:26180612

  5. Human immunodeficiency virus, herpes virus infections, and pulmonary vascular disease.

    PubMed

    Flores, Sonia C; Almodovar, Sharilyn

    2013-01-01

    The following state-of-the-art seminar was delivered as part of the Aspen Lung Conference on Pulmonary Hypertension and Vascular Diseases held in Aspen, Colorado in June 2012. This paper will summarize the lecture and present results from a nonhuman primate model of infection with Simian (Human) Immunodeficiency Virus - nef chimeric virions as well as the idea that polymorphisms in the HIV-1 nef gene may be driving the immune response that results in exuberant inflammation and aberrant endothelial cell (EC) function. We will present data gathered from primary HIV nef isolates where we tested the biological consequences of these polymorphisms and how their presence in human populations may predict patients at risk for developing this disease. In this article, we also discuss how a dysregulated immune system, in conjunction with a viral infection, could contribute to pulmonary arterial hypertension (PAH). Both autoimmune diseases and some viruses are associated with defects in the immune system, primarily in the function of regulatory T cells. These T-cell defects may be a common pathway in the formation of plexiform lesions. Regardless of the route by which viruses may lead to PAH, it is important to recognize their role in this rare disease.

  6. Human immunodeficiency virus, herpes virus infections, and pulmonary vascular disease

    PubMed Central

    Flores, Sonia C.; Almodovar, Sharilyn

    2013-01-01

    The following state-of-the-art seminar was delivered as part of the Aspen Lung Conference on Pulmonary Hypertension and Vascular Diseases held in Aspen, Colorado in June 2012. This paper will summarize the lecture and present results from a nonhuman primate model of infection with Simian (Human) Immunodeficiency Virus - nef chimeric virions as well as the idea that polymorphisms in the HIV-1 nef gene may be driving the immune response that results in exuberant inflammation and aberrant endothelial cell (EC) function. We will present data gathered from primary HIV nef isolates where we tested the biological consequences of these polymorphisms and how their presence in human populations may predict patients at risk for developing this disease. In this article, we also discuss how a dysregulated immune system, in conjunction with a viral infection, could contribute to pulmonary arterial hypertension (PAH). Both autoimmune diseases and some viruses are associated with defects in the immune system, primarily in the function of regulatory T cells. These T-cell defects may be a common pathway in the formation of plexiform lesions. Regardless of the route by which viruses may lead to PAH, it is important to recognize their role in this rare disease. PMID:23662195

  7. The pathobiology of vascular dementia

    PubMed Central

    Iadecola, Costantino

    2013-01-01

    Vascular cognitive impairment defines alterations in cognition, ranging from subtle deficits to full-blown dementia, attributable to cerebrovascular causes. Often coexisting with Alzheimer’s disease, mixed vascular and neurodegenerative dementia has emerged as the leading cause of age-related cognitive impairment. Central to the disease mechanism is the crucial role that cerebral blood vessels play in brain health, not only for the delivery of oxygen and nutrients, but also for the trophic signaling that links inextricably the well being of neurons and glia to that of cerebrovascular cells. This review will examine how vascular damage disrupts these vital homeostatic interactions, focusing on the hemispheric white matter, a region at heightened risk for vascular damage, and on the interplay between vascular factors and Alzheimer’s disease. Finally, preventative and therapeutic prospects will be examined, highlighting the importance of midlife vascular risk factor control in the prevention of late-life dementia. PMID:24267647

  8. Heterogeneity in vascular smooth muscle cell embryonic origin in relation to adult structure, physiology, and disease

    PubMed Central

    Pfaltzgraff, Elise R.; Bader, David M.

    2015-01-01

    Regional differences in vascular physiology and disease response exist throughout the vascular tree. While these differences in physiology and disease correspond to regional vascular environmental conditions, there is also compelling evidence that the embryonic origins of the smooth muscle inherent to the vessels may play a role. Here we review what is known regarding the role of embryonic origin of vascular smooth muscle cells during vascular development. The focus of this review is to highlight the heterogeneity in the origins of vascular smooth muscle cells and the resulting regional physiologies of the vessels. Our goal is to stimulate future investigation into this area and provide a better understanding of vascular organogenesis and disease. PMID:25546231

  9. Vascular aging: Chronic oxidative stress and impairment of redox signaling—consequences for vascular homeostasis and disease

    PubMed Central

    Bachschmid, Markus M.; Schildknecht, Stefan; Matsui, Reiko; Zee, Rebecca; Haeussler, Dagmar; Cohen, Richard A.; Pimental, David; van der Loo, Bernd

    2013-01-01

    Characteristic morphological and molecular alterations such as vessel wall thickening and reduction of nitric oxide occur in the aging vasculature leading to the gradual loss of vascular homeostasis. Consequently, the risk of developing acute and chronic cardiovascular diseases increases with age. Current research of the underlying molecular mechanisms of endothelial function demonstrates a duality of reactive oxygen and nitrogen species in contributing to vascular homeostasis or leading to detrimental effects when formed in excess. Furthermore, changes in function and redox status of vascular smooth muscle cells contribute to age-related vascular remodeling. The age-dependent increase in free radical formation causes deterioration of the nitric oxide signaling cascade, alters and activates prostaglandin metabolism, and promotes novel oxidative posttranslational protein modifications that interfere with vascular and cell signaling pathways. As a result, vascular dysfunction manifests. Compensatory mechanisms are initially activated to cope with age-induced oxidative stress, but become futile, which results in irreversible oxidative modifications of biological macromolecules. These findings support the ‘free radical theory of aging’ but also show that reactive oxygen and nitrogen species are essential signaling molecules, regulating vascular homeostasis. PMID:22380696

  10. Mechanical Injury Induces Brain Endothelial-Derived Microvesicle Release: Implications for Cerebral Vascular Injury during Traumatic Brain Injury

    PubMed Central

    Andrews, Allison M.; Lutton, Evan M.; Merkel, Steven F.; Razmpour, Roshanak; Ramirez, Servio H.

    2016-01-01

    . These results indicate that following TBI, the cerebral endothelium undergoes vascular remodeling through shedding of eMVs containing TJPs and endothelial markers. The detection of this shedding potentially allows for a novel methodology for real-time monitoring of cerebral vascular health (remodeling), BBB status and neuroinflammation following a TBI event. PMID:26973460

  11. Family history of atherosclerotic vascular disease is associated with the presence of abdominal aortic aneurysm.

    PubMed

    Ye, Zi; Bailey, Kent R; Austin, Erin; Kullo, Iftikhar J

    2016-02-01

    We investigated whether family history (FHx) of atherosclerotic cardiovascular disease (ASCVD) was associated with presence of abdominal aortic aneurysm (AAA). The study cohort comprised of 696 patients with AAA (70±8 years, 84% men) and 2686 controls (68±10 years, 61% men) recruited from noninvasive vascular and stress electrocardiogram (ECG) laboratories at Mayo Clinic. AAA was defined as a transverse diameter of abdominal aorta ⩾ 3 cm or history of AAA repair. Controls were not known to have AAA. FHx was defined as having at least one first-degree relative with aortic aneurysm or with onset of ASCVD (coronary, cerebral or peripheral artery disease) before age 65 years. FHx of aortic aneurysm or ASCVD were each associated with presence of AAA after adjustment for age, sex, conventional risk factors and ASCVD: adjusted odds ratios (OR; 95% confidence interval): 2.17 (1.66-2.83, p < 0.01) and 1.31 (1.08-1.59, p < 0.01), respectively. FHx of ASCVD remained associated with AAA after additional adjustment for FHx of aortic aneurysm: adjusted OR: 1.27 (1.05-1.55, p = 0.01). FHx of ASCVD in multiple arterial locations was associated with higher odds of having AAA: the adjusted odds were 1.23 times higher for each additionally affected arterial location reported in the FHx (1.08-1.40, p = 0.01). Our results suggest both unique and shared environmental and genetic factors mediating susceptibility to AAA and ASCVD.

  12. Education modifies the relation of vascular pathology to cognitive function: cognitive reserve in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

    PubMed

    Zieren, Nikola; Duering, Marco; Peters, Nils; Reyes, Sonia; Jouvent, Eric; Hervé, Dominique; Gschwendtner, Andreas; Mewald, Yvonne; Opherk, Christian; Chabriat, Hugues; Dichgans, Martin

    2013-02-01

    A clinical impact of cognitive reserve (CR) has been demonstrated in Alzheimer's disease, whereas its role in vascular cognitive impairment (VCI) is largely unknown. In this study, we investigated the impact of CR in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic variant of pure VCI. A total of 247 NOTCH3 mutation carriers from a two-center study were investigated using detailed neuropsychological and neuroimaging protocols. CR was operationalized as years of formal education. Brain pathology was assessed by MRI using normalized brain volume and lacunar lesion volume as proxies. Multivariate analyses were done for each structural measure with scores of processing speed, executive function, and memory as dependent variables. Additional linear regression models were conducted with interaction terms for education × brain volume and education × lacunar lesion volume. Education had an independent impact on cognitive performance in subjects with mild and moderate degrees of brain pathology, whereas there was no significant influence of education on cognition in patients with severe MRI changes. This interaction was found for processing speed, the cognitive domain most impaired in our patients. Our findings demonstrate an interaction of education and brain pathology in regard to cognitive impairment: the effect of education seems most pronounced in early disease stages but may ultimately be overwhelmed by the pathological changes. The results extend the concept of CR to VCI.

  13. Endothelial cells and human cerebral small vessel disease.

    PubMed

    Hainsworth, Atticus H; Oommen, Asho T; Bridges, Leslie R

    2015-01-01

    Brain endothelial cells have unique properties in terms of barrier function, local molecular signaling, regulation of local cerebral blood flow (CBF) and interactions with other members of the neurovascular unit. In cerebral small vessel disease (arteriolosclerosis; SVD), the endothelial cells in small arteries survive, even when mural pathology is advanced and myocytes are severely depleted. Here, we review aspects of altered endothelial functions that have been implicated in SVD: local CBF dysregulation, endothelial activation and blood-brain barrier (BBB) dysfunction. Reduced CBF is reported in the diffuse white matter lesions that are a neuroradiological signature of SVD. This may reflect an underlying deficit in local CBF regulation (possibly via the nitric oxide/cGMP signaling pathway). While many laboratories have observed an association of symptomatic SVD with serum markers of endothelial activation, it is apparent that the origin of these circulating markers need not be brain endothelium. Our own neuropathology studies did not confirm local endothelial activation in small vessels exhibiting SVD. Local BBB failure has been proposed as a cause of SVD and associated parenchymal lesions. Some groups find that computational analyses of magnetic resonance imaging (MRI) scans, following systemic injection of a gadolinium-based contrast agent, suggest that extravasation into brain parenchyma is heightened in people with SVD. Our recent histochemical studies of donated brain tissue, using immunolabeling for large plasma proteins [fibrinogen, immunoglobulin G (IgG)], do not support an association of SVD with recent plasma protein extravasation. It is possible that a trigger leakage episode, or a size-selective loosening of the BBB, participates in SVD pathology.

  14. Chronic supplementation of paeonol combined with danshensu for the improvement of vascular reactivity in the cerebral basilar artery of diabetic rats.

    PubMed

    Hu, Jing; Li, Ya-Ling; Li, Zi-Lin; Li, Hua; Zhou, Xuan-Xuan; Qiu, Peng-Cheng; Yang, Qian; Wang, Si-Wang

    2012-11-08

    One of the leading causes of death in the world is cerebrovascular disease. Numerous Chinese traditional medicines, such as Cortex Moutan (root bark of Paeonia suffruticosa Andrew) and Radix Salviae miltiorrhizae (root and rhizome of Salvia miltiorrhiza Bunge), protect against cerebrovascular diseases and exhibit anti-atherosclerotic effects. Traditional medicines have been routinely used for a long time in China. In addition, these two herbs are prescribed together in clinical practice. Therefore, the pharmacodynamic interactions between the active constituents of these two herbs, which are paeonol (Pae) and danshensu (DSS), should be particularly studied. The study of Pae and DSS can provide substantial foundations in understanding their mechanisms and empirical evidence to support clinical practice. This study investigated the effects and possible mechanisms of the pharmacodynamic interaction between Pae and DSS on cerebrovascular malfunctioning in diabetes. Experimental diabetes was induced in rats, which was then treated with Pae, DSS, and Pae + DSS for eight weeks. Afterward, cerebral arteries from all groups were isolated and equilibrated in an organ bath with Krebs buffer and ring tension. Effects of Pae, DSS, and Pae + DSS were observed on vessel relaxation with or without endothelium as well as on the basal tonus of vessels from normal and diabetic rats. Indexes about oxidative stress were also determined. We report that the cerebral arteries from diabetic rats show decreased vascular reactivity to acetylcholine (ACh) which was corrected in Pae, DSS, and Pae + DSS treated groups. Furthermore, phenylephrine (PE)-induced contraction response decreased in the treated groups. Phenylephrine and CaCl(2)-induced vasoconstrictions are partially inhibited in the three treated groups under Ca2+-free medium. Pre-incubated with tetraethylammonium, a non-selective K+ channel blocker, the antagonized relaxation responses increased in DSS and Pae + DSS treated diabetic

  15. Sympathetic regulation of vascular function in health and disease

    PubMed Central

    Bruno, Rosa M.; Ghiadoni, Lorenzo; Seravalle, Gino; Dell'Oro, Raffaella; Taddei, Stefano; Grassi, Guido

    2012-01-01

    The sympathetic nervous system (SNS) is known to play a pivotal role in short- and long-term regulation of different functions of the cardiovascular system. In the past decades increasing evidence demonstrated that sympathetic neural control is involved not only in the vasomotor control of small resistance arteries but also in modulation of large artery function. Sympathetic activity and vascular function, both of which are key factors in the development and prognosis of cardiovascular events and disease, are linked at several levels. Evidence from experimental studies indicates that the SNS is critically influenced, at the central and also at the peripheral level, by the most relevant factors regulating vascular function, such as nitric oxide (NO), reactive oxygen species (ROS), endothelin (ET), the renin-angiotensin system. Additionally, there is indirect evidence of a reciprocal relationship between endothelial function and activity of the SNS. A number of cardiovascular risk factors and diseases are characterized both by increased sympathetic outflow and decreased endothelial function. In healthy subjects, muscle sympathetic nerve activity (MSNA) appears to be related to surrogate markers of endothelial function, and an acute increase in sympathetic activity has been associated with a decrease in endothelial function in healthy subjects. However, direct evidence of a cause-effect relationship from human studies is scanty. In humans large artery stiffness has been associated with increased sympathetic discharge, both in healthy subjects and in renal transplant recipients. Peripheral sympathetic discharge is also able to modulate wave reflection. On the other hand, large artery stiffness can interfere with autonomic regulation by impairing carotid baroreflex sensitivity. PMID:22934037

  16. Markers of vascular disease in plasma from patients with chronic kidney disease identified by proteomic analysis.

    PubMed

    Schiffer, Eric; Liabeuf, Sophie; Lacroix, Chrystelle; Temmar, Mohamed; Renard, Cedric; Monsarrat, Bernard; Choukroun, Gabriel; Lemke, Horst-Dieter; Vanholder, Raymond; Mischak, Harald; Massy, Ziad A

    2011-04-01

    Chronic kidney disease (CKD) patients belong to the group of patients with a high prevalence of cardiovascular disease (CVD). Arterial calcification and aortic stiffness are currently used as surrogates for vascular alterations. However, still little is known about prediction and the patho-physiologic mechanisms leading to CVD. We applied capillary electrophoresis coupled mass spectrometry profiling to blood specimens collected from 34 CKD stage 5D patients suffering from vascular alterations to allow insights into the molecular pathology of the disease. Statistical comparison of plasma profiles from mild and severe CVD cases according to either arterial calcification or aortic stiffness unveiled 13 novel biomarkers for vascular disease. Tandem mass spectrometry identified four of these as fragments of collagen alpha-1 type I and III and one as fragment of apolipoprotein CIII. Integrated in a distinct pattern the candidates were validated using the moderate CVD cases among the 34 CKD patients (N=11) and an additional independent blinded cohort of CKD stage 4-5 patients (N=21), who all had not been considered during biomarker discovery. The panel distinguished mild and severe CVD with sensitivity of 89% and specificity of 67% in this independent cohort. This diagnostic phase I/II study supports the notion that vascular alterations are reflected by distinct changes in plasma profiles of CKD patients.

  17. Formyl-Peptide Receptor 2/3/Lipoxin A4 Receptor Regulates Neutrophil-Platelet Aggregation and Attenuates Cerebral Inflammation: Impact for Therapy in Cardiovascular Disease.

    PubMed

    Vital, Shantel A; Becker, Felix; Holloway, Paul M; Russell, Janice; Perretti, Mauro; Granger, D Neil; Gavins, Felicity N E

    2016-05-31

    Platelet activation at sites of vascular injury is essential for hemostasis, but it is also a major pathomechanism underlying ischemic injury. Because anti-inflammatory therapies limit thrombosis and antithrombotic therapies reduce vascular inflammation, we tested the therapeutic potential of 2 proresolving endogenous mediators, annexin A1 N-terminal derived peptide (AnxA1Ac2-26) and aspirin-triggered lipoxin A4 (15-epi-lipoxin A4), on the cerebral microcirculation after ischemia/reperfusion injury. Furthermore, we tested whether the lipoxin A4 receptor formyl-peptide receptor 2/3 (Fpr2/3; ortholog to human FPR2/lipoxin A4 receptor) evoked neuroprotective functions after cerebral ischemia/reperfusion injury. Using intravital microscopy, we found that cerebral ischemia/reperfusion injury was accompanied by neutrophil and platelet activation and neutrophil-platelet aggregate formation within cerebral microvessels. Moreover, aspirin-triggered lipoxin A4 activation of neutrophil Fpr2/3 regulated neutrophil-platelet aggregate formation in the brain and inhibited the reactivity of the cerebral microvasculature. The same results were obtained with AnxA1Ac2-26 administration. Blocking Fpr2/lipoxin A4 receptor with the antagonist Boc2 reversed this effect, and treatments were ineffective in Fpr2/3 knockout mice, which displayed an exacerbated disease severity, evidenced by increased infarct area, blood-brain barrier dysfunction, increased neurological score, and elevated levels of cytokines. Furthermore, aspirin treatment significantly reduced cerebral leukocyte recruitment and increased endogenous levels of aspirin-triggered lipoxin A4, effects again mediated by Fpr2/3. Fpr2/lipoxin A4 receptor is a therapeutic target for initiating endogenous proresolving, anti-inflammatory pathways after cerebral ischemia/reperfusion injury. © 2016 American Heart Association, Inc.

  18. Carotid Plaque Morphology and Ischemic Vascular Brain Disease on MRI.

    PubMed

    van den Bouwhuijsen, Q J A; Vernooij, M W; Verhaaren, B F J; Vrooman, H A; Niessen, W J; Krestin, G P; Ikram, M A; Franco, O H; van der Lugt, A

    2017-09-01

    Vulnerable carotid plaque components are reported to increase the risk of cerebrovascular events. Yet, the relation between plaque composition and subclinical ischemic brain disease is not known. We studied, in the general population, the association between carotid atherosclerotic plaque characteristics and ischemic brain disease on MR imaging. From the population-based Rotterdam Study, 951 participants underwent both carotid MR imaging and brain MR imaging. The presence of intraplaque hemorrhage, lipid core, and calcification and measures of plaque size was assessed in both carotid arteries. The presence of plaque characteristics in relation to lacunar and cortical infarcts and white matter lesion volume was investigated and adjusted for cardiovascular risk factors. Stratified analyses were conducted to explore effect modification by sex. Additional analyses were conducted per carotid artery in relation to vascular brain disease in the ipsilateral hemisphere. Carotid intraplaque hemorrhage was significantly associated with the presence of cortical infarcts (OR, 1.9; 95% confidence interval, 1.1-3.3). None of the plaque characteristics were related to the presence of lacunar infarcts. Calcification was the only characteristic that was associated with higher white matter lesion volume. There was no significant interaction by sex. The presence of carotid intraplaque hemorrhage on MR imaging is independently associated with MR imaging-defined cortical infarcts, but not with lacunar infarcts. Plaque calcification, but not vulnerable plaque components, is related to white matter lesion volume. © 2017 by American Journal of Neuroradiology.

  19. The association between insomnia symptoms and risk of cardio-cerebral vascular events: A meta-analysis of prospective cohort studies.

    PubMed

    He, Qiao; Zhang, Peng; Li, Guangxiao; Dai, Huixu; Shi, Jingpu

    2017-07-01

    Background Insomnia symptoms have been suggested to be associated with the risk of cardio-cerebral events. However, the results of previous studies have been inconsistent. Therefore, we conducted a meta-analysis to examine whether there were associations between cardio-cerebral vascular events and insomnia symptoms, including difficulty initiating sleep, difficulty maintaining sleep, early-morning awakening or non-restorative sleep. Design A meta-analysis of prospective cohort studies. Methods PubMed, Web of science and the Cochrane Library were searched without language restriction. Prospective cohort studies of adults with at least a 2-year follow-up duration were included. Random effect models were used in order to pool the results for each insomnia symptom. Subgroup and sensitivity analyses were conducted in order to assess potential heterogeneity, and funnel plots and Egger's tests were used in order to assess publication bias. Results Fifteen studies (23 cohorts) were included. Positive associations were observed between difficulty initiating sleep, difficulty maintaining sleep and non-restorative sleep with risk of cardio-cerebral vascular events. The pooled relative risks and 95% confidence intervals were 1.27 (1.15-1.40), 1.11 (1.04-1.19) and 1.18 (1.05-1.33), respectively. However, less evidence existed to support the conclusions about the association between early-morning awakening and cardio-cerebral vascular events. Conclusion Our meta-analysis demonstrated that insomnia symptoms of difficulty initiating sleep, difficulty maintaining sleep and non-restorative sleep were associated with an increased risk of future cardio-cerebral vascular events.

  20. Blood-Brain Barrier Dysfunction and Cerebral Small Vessel Disease (Arteriolosclerosis) in Brains of Older People

    PubMed Central

    Khoong, Cheryl H.L.; Poon, Wayne; Esiri, Margaret M.; Markus, Hugh S.; Hainsworth, Atticus H.

    2014-01-01

    The blood-brain barrier (BBB) protects brain tissue from potentially harmful plasma components. Small vessel disease ([SVD], arteriolosclerosis) is common in the brains of older people and is associated with lacunar infarcts, leukoaraiosis and vascular dementia. To determine whether plasma extravasation is associated with SVD, we immunolabeled the plasma proteins fibrinogen and IgG, which are assumed to reflect BBB dysfunction, in deep grey matter (anterior caudate-putamen, [DGM]) and deep subcortical white matter (DWM) in the brains of a well-characterized patient cohort with minimal Alzheimer disease pathology (Braak stage 0-II) (n = 84; age ≥65 years). Morphometric measures of fibrinogen labeling were compared between people with neuropathologically defined SVD and aged control subjects. Parenchymal cellular labeling with fibrinogen and IgG was detectable in DGM and DWM in many subjects (>70%). Quantitative measures of fibrinogen were not associated with SVD in DGM or DWM; SVD severity was correlated between DGM and DWM (p < 0.0001). Fibrinogen in DGM showed a modest association with a history of hypertension; DWM fibrinogen was associated with dementia and cerebral amyloid angiopathy (all p < 0.05). In DWM, SVD was associated with leukoaraiosis identified in life (p < 0.05), but fibrinogen was not. Our data suggest that in aged brains plasma extravasation and hence local BBB dysfunction is common but do not support an association with SVD. PMID:25289893

  1. EXCEPTIONAL AGGRESSIVENESS OF CEREBRAL CAVERNOUS MALFORMATION DISEASE ASSOCIATED WITH PDCD10 MUTATIONS

    PubMed Central

    Rebeiz, Tania; Stockton, Rebecca A.; McDonald, David A.; Mikati, Abdul Ghani; Zhang, Lingjiao; Austin, Cecilia; Akers, Amy L.; Gallione, Carol J.; Rorrer, Autumn; Gunel, Murat; Min, Wang; De Souza, Jorge Marcondes; Lee, Connie

    2014-01-01

    Purpose The phenotypic manifestations of cerebral cavernous malformation (CCM) disease caused by rare PDCD10 mutations have not been systematically examined, and a mechanistic link to Rho kinase (ROCK) mediated hyperpermeability, a potential therapeutic target, has not been established. Methods We analyze PDCD10-siRNA treated endothelial cells for stress fibers, ROCK activity and permeability. ROCK activity is assessed in CCM lesions. Brain permeability and CCM lesion burden is quantified, and clinical manifestations are assessed in prospectively enrolled subjects with PDCD10 mutations. Results We determine that PDCD10 protein suppresses endothelial stress fibers, ROCK activity and permeability in vitro. Pdcd10 heterozygous mice have greater lesion burden than other Ccm genotypes. We demonstrate robust ROCK activity in murine and human CCM vasculature, and increased brain vascular permeability in humans with PDCD10 mutation. Clinical phenotype is exceptionally aggressive compared to the more common KRIT1 and CCM2 familial and sporadic CCM, with greater lesion burden and more frequent hemorrhages earlier in life. We first report other phenotypic features including scoliosis, cognitive disability and skin lesions, unrelated to lesion burden or bleeding. Conclusion These findings define a unique CCM disease with exceptional aggressiveness, and they inform preclinical therapeutic testing, clinical counseling and the design of trials. PMID:25122144

  2. Distinguishing between vascular dementia and Alzheimer's disease by means of the WAIS: a meta-analysis.

    PubMed

    Oosterman, Joukje M; Scherder, Erik J A

    2006-10-01

    This study was intended to, meta-analytically, review whether the subtests of the Wechsler Adult Intelligence Scale are useful in differentiating between vascular dementia and Alzheimer's disease. We expected the Alzheimer's disease group to outperform the vascular dementia group on those subtests that require executive functions, whereas inferior performance of the Alzheimer's disease patients was expected on memory tests. Two steps in the analysis were undertaken in an attempt to clarify this issue. The first step consisted of including all studies examining Wechsler Adult Intelligence Scale subtest performance in vascular dementia and Alzheimer's disease patients. Secondly, a subcortical vascular dementia subgroup was distinguished and performance of this subgroup was compared to that of the Alzheimer's disease group.Overall, the analyses showed that both the vascular dementia and, more strongly, the subcortical vascular dementia group revealed decreased executive functions on several subtests compared to the Alzheimer's disease group. The Alzheimer's disease group showed inferior performance on a single semantic memory test only compared to both the vascular dementia and the subcortical vascular dementia groups. These results indicate that several subtests of the Wechsler Adult Intelligence Scale can differentiate between these two clinical groups, and that most of these tests reveal more impaired performance in the vascular dementia group.

  3. Ultrafast Doppler reveals the mapping of cerebral vascular resistivity in neonates

    PubMed Central

    Demené, Charlie; Pernot, Mathieu; Biran, Valérie; Alison, Marianne; Fink, Mathias; Baud, Oli