Gaorui Liu, J. Clarke, D. Oomens, M. Vicaretti, T. Daly, Tae Hyun Cho, I. Mohan
The assessment of the saphenofemoral junction (SFJ) is important in the diagnosis and treatment of venous reflux of the great saphenous vein (GSV). In the clinical practice of venous medicine, the SFJ is used to represent the region at which the saphenous arch connects with the common femoral vein (CFV). A number of notable variations of the SFJ have been documented, and rare variable courses of the GSV have been described recently. Our case study reports two unusual GSV terminations. In both cases, the SFJ was located below the confluence of the profunda femoris vein (PFV) with the femoral vein (FV). Case 1 showed the SFJ was formed by the GSV and FV; whereas case 2 showed the PFV was joined by the GSV after a transposition with the FV. Anatomical variations of the SFJ are rare; however, they are increasingly diagnosed with the use of duplex ultrasound. The identification of SFJ variants warrants a safe endovenous procedure and prevents surgical complications.
{"title":"Termination of the great saphenous vein at variable levels","authors":"Gaorui Liu, J. Clarke, D. Oomens, M. Vicaretti, T. Daly, Tae Hyun Cho, I. Mohan","doi":"10.4081/vl.2022.10786","DOIUrl":"https://doi.org/10.4081/vl.2022.10786","url":null,"abstract":"The assessment of the saphenofemoral junction (SFJ) is important in the diagnosis and treatment of venous reflux of the great saphenous vein (GSV). In the clinical practice of venous medicine, the SFJ is used to represent the region at which the saphenous arch connects with the common femoral vein (CFV). A number of notable variations of the SFJ have been documented, and rare variable courses of the GSV have been described recently. Our case study reports two unusual GSV terminations. In both cases, the SFJ was located below the confluence of the profunda femoris vein (PFV) with the femoral vein (FV). Case 1 showed the SFJ was formed by the GSV and FV; whereas case 2 showed the PFV was joined by the GSV after a transposition with the FV. Anatomical variations of the SFJ are rare; however, they are increasingly diagnosed with the use of duplex ultrasound. The identification of SFJ variants warrants a safe endovenous procedure and prevents surgical complications.","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"562 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133356165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The gold standard vascular access for hemodialysis is the arteriovenous fistula (AVF). Venous hypertension (VH) is an unusual complication of AVF, which can be misdiagnosed as cellulitis due to the similarities in clinical presentation. Here we present a case of venous hypertension in a 40-years-old gentleman, who presented with progressive pain and swelling of three lateral fingers of his left hand without other inflammatory signs after a year of AVF creation. Further evaluation with a duplex scan supported the clinical diagnosis of VH. He had undergone a surgical ligation of AVF and completely recovered from the symptoms.
{"title":"An unusual cause of venous hypertension","authors":"Vinojan Satchithanantham, Dhadchayini Rajahram","doi":"10.4081/vl.2022.10753","DOIUrl":"https://doi.org/10.4081/vl.2022.10753","url":null,"abstract":"The gold standard vascular access for hemodialysis is the arteriovenous fistula (AVF). Venous hypertension (VH) is an unusual complication of AVF, which can be misdiagnosed as cellulitis due to the similarities in clinical presentation. Here we present a case of venous hypertension in a 40-years-old gentleman, who presented with progressive pain and swelling of three lateral fingers of his left hand without other inflammatory signs after a year of AVF creation. Further evaluation with a duplex scan supported the clinical diagnosis of VH. He had undergone a surgical ligation of AVF and completely recovered from the symptoms.","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"53 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115201281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Randa S. Eshaq, Minsup Lee, Wendy Leskova, N. Harris, J. Alexander
Background: Hypertension (HT) promotes structural and functional changes in the cerebral microcirculation that can provoke irreversible cerebrovascular injury, leading to neuronal loss and brain atrophy,1 cognitive impairment, vascular dementia,2 and Alzheimer’s disease.3 Currently, the mechanisms and consequences of such remodeling are not fully understood. Transforming growth factor (TGF) is a morphogen that regulates cellular differentiation, induces endothelial-to-mesenchymal transition (EndoMT), and works as a contractile-to-synthetic switch in vascular smooth muscle cells (VSMC) phenotype.4 Plasma levels of TGF are increased in HT patients, and in spontaneously hypertensive rats (SHR) that exhibit vascular fibrosis.5 Although coincidental, causal roles through which elevated TGF may drive cerebrovascular remodeling in the HT brain are suspected, but unproven. We hypothesize that HT-induced TGF drives cerebrovascular remodeling, which decreases blood-brain barrier and impairs cerebrovascular autoregulation. Methods: Brain cortices and penetrating cerebral microvessels (BMVs) were isolated from male and female SHR and Wistar-Kyoto rats (WKY, control), and subjected to western blotting and immunofluorescence labeling for endothelial cell (EC) and VSMC differentiation markers, TGF canonical pathway markers SMAD2, 3 and 4, as well as basement membrane protein expression, and glial fibrillary acidic protein (GFAP) as a marker of astrocyte inflammation. Additionally, TGF-treated rat retinal microvascular endothelial cells (RRMECs), and human brain microvascular endothelial cells (hCMEC/D3) ± the TGF inhibitor vactosertib, were also subjected to western blotting and immunofluorescence labeling to assess endothelial cell (EC) and VSMC differentiation markers, as well as basement membrane protein expression. Results: TGF was significantly increased in SHR BMVs. Moreover, GFAP levels were significantly increased in the SHR cortex. The EC junctional proteins platelet endothelial cell adhesion molecule-1 (PECAM-1) and vascular endothelial-cadherin (VE-cadherin), were significantly decreased in SHR. In contrast, CRBP-1, a marker for synthetic VSMC, and collagen IV and fibronectin levels significantly increased in SHR. Interestingly, female SHR rats had significantly increased levels of SMAD2/3, which was not evident in male SHRs, indicating a possible role for the non-canonical TGF pathway in male SHRs. Additionally, TGF significantly increased -smooth muscle actin (-SMA) and decreased VE-cadherin expression in RRMECs and D3 cells, consistent with EndoMT. TGF inhibition with vactosertib reversed these effects and significantly suppressed -SMA, and maintained VE-Cadherin similar to control RRMECs and D3s. Conclusions: We now have strong evidence for HT-induced cerebrovascular remodeling, where TGF mediates loss of both smooth muscle and endothelial differentiated phenotypes. The reversal of these effects using TGF blockers suggests that
{"title":"The role of transforming growth factor- in hypertension-induced cerebrovascular remodeling","authors":"Randa S. Eshaq, Minsup Lee, Wendy Leskova, N. Harris, J. Alexander","doi":"10.4081/vl.2022.10964","DOIUrl":"https://doi.org/10.4081/vl.2022.10964","url":null,"abstract":"Background: Hypertension (HT) promotes structural and functional changes in the cerebral microcirculation that can provoke irreversible cerebrovascular injury, leading to neuronal loss and brain atrophy,1 cognitive impairment, vascular dementia,2 and Alzheimer’s disease.3 Currently, the mechanisms and consequences of such remodeling are not fully understood. Transforming growth factor (TGF) is a morphogen that regulates cellular differentiation, induces endothelial-to-mesenchymal transition (EndoMT), and works as a contractile-to-synthetic switch in vascular smooth muscle cells (VSMC) phenotype.4 Plasma levels of TGF are increased in HT patients, and in spontaneously hypertensive rats (SHR) that exhibit vascular fibrosis.5 Although coincidental, causal roles through which elevated TGF may drive cerebrovascular remodeling in the HT brain are suspected, but unproven. We hypothesize that HT-induced TGF drives cerebrovascular remodeling, which decreases blood-brain barrier and impairs cerebrovascular autoregulation. \u0000Methods: Brain cortices and penetrating cerebral microvessels (BMVs) were isolated from male and female SHR and Wistar-Kyoto rats (WKY, control), and subjected to western blotting and immunofluorescence labeling for endothelial cell (EC) and VSMC differentiation markers, TGF canonical pathway markers SMAD2, 3 and 4, as well as basement membrane protein expression, and glial fibrillary acidic protein (GFAP) as a marker of astrocyte inflammation. Additionally, TGF-treated rat retinal microvascular endothelial cells (RRMECs), and human brain microvascular endothelial cells (hCMEC/D3) ± the TGF inhibitor vactosertib, were also subjected to western blotting and immunofluorescence labeling to assess endothelial cell (EC) and VSMC differentiation markers, as well as basement membrane protein expression. \u0000Results: TGF was significantly increased in SHR BMVs. Moreover, GFAP levels were significantly increased in the SHR cortex. The EC junctional proteins platelet endothelial cell adhesion molecule-1 (PECAM-1) and vascular endothelial-cadherin (VE-cadherin), were significantly decreased in SHR. In contrast, CRBP-1, a marker for synthetic VSMC, and collagen IV and fibronectin levels significantly increased in SHR. Interestingly, female SHR rats had significantly increased levels of SMAD2/3, which was not evident in male SHRs, indicating a possible role for the non-canonical TGF pathway in male SHRs. Additionally, TGF significantly increased -smooth muscle actin (-SMA) and decreased VE-cadherin expression in RRMECs and D3 cells, consistent with EndoMT. TGF inhibition with vactosertib reversed these effects and significantly suppressed -SMA, and maintained VE-Cadherin similar to control RRMECs and D3s. \u0000Conclusions: We now have strong evidence for HT-induced cerebrovascular remodeling, where TGF mediates loss of both smooth muscle and endothelial differentiated phenotypes. The reversal of these effects using TGF blockers suggests that","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"223 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122886891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Mantovani, P. De Bonis, M. Cavallo, Paolo Zamboni, A. Scerrati
Cerebral venous drainage impairment is related to a wide spectrum of pathologies, both acute or chronic. Among the most intriguing and less explained there are those caused by a long-lasting compression on internal jugular vein (IJV), mono or bilaterally. Recently, a jugular variant of the Eagle syndrome has been described,1,2 in which an elongated styloid process, coming from the mastoid tip down through the neck, compresses the IJV (more frequently J3) in its passage on the C1 anterior arch. Interestingly, those patients often complaint of typical symptoms of intracranial hypertension, such as headache (not frequent in classic Eagle syndrome), tinnitus, dizziness. They also seem to have an increased risk of perimesencephalic hemorrhages. Conceptually, it is not the styloid process length in itself to determine the compression, but rather its spatial orientation. We could therefore expect to find patients suffering from Eagle jugular syndrome who present normal or short styloid process, but in close proximity to C1. To test this hypothesis, we are developing a novel software to analyze 3-D spatial orientation of styloid process in patient with a previously diagnosed Eagle jugular syndrome compared to healthy controls. Methods We collected cervical computed tomography angiography (CTA) images from 8 patients with EJS confirmed by venous angiography at our institution, and a control group of 7 random patients, homogenous for sex and age. A blind operator created with a dedicated pre-existing software3, an editable 3-D model (.stl file) of the 3 main region of interest (ROI), namely: right styloid, left styloid, C1 anterior arch. Starting from this dataset, our software, written using the open-source package management system Anaconda4 ver. 2-2.4.0, compares all the possible couples of points between each styloid process and the C1 arch, detecting the minimum and maximum distance. Then, it provides the mean spatial orientation of the process respect the CT-axis: x-axis (from left to right), y-axis (from occiput to nose) and z-axis (cranio-caudal). Results By now we included 15 patients (8 cases, 7 controls), homogeneous for sex and age. Preliminary data (Table 1), although not statistically significant yet, seems to indicate that Eagle jugular patients effectively have a more vertical styloid process, meaning an angle between styloid and y-axis greater than controls, rather than a longer one. Conclusions Our preliminary results could confirm that spatial orientation is more important in Eagle jugular patients than styloid process length. This study is currently ongoing and we planned to enroll at least 20 subjects for each arm. At the same time, we are collecting data from patients with carotic variant of Eagle syndrome, to better characterize morphometric structure of styloid in various subset of this pathology.
{"title":"Eagle jugular syndrome: a morphometric computed study on styloid process orientation","authors":"G. Mantovani, P. De Bonis, M. Cavallo, Paolo Zamboni, A. Scerrati","doi":"10.4081/vl.2022.10955","DOIUrl":"https://doi.org/10.4081/vl.2022.10955","url":null,"abstract":"Cerebral venous drainage impairment is related to a wide spectrum of pathologies, both acute or chronic. Among the most intriguing and less explained there are those caused by a long-lasting compression on internal jugular vein (IJV), mono or bilaterally. Recently, a jugular variant of the Eagle syndrome has been described,1,2 in which an elongated styloid process, coming from the mastoid tip down through the neck, compresses the IJV (more frequently J3) in its passage on the C1 anterior arch. Interestingly, those patients often complaint of typical symptoms of intracranial hypertension, such as headache (not frequent in classic Eagle syndrome), tinnitus, dizziness. They also seem to have an increased risk of perimesencephalic hemorrhages. Conceptually, it is not the styloid process length in itself to determine the compression, but rather its spatial orientation. We could therefore expect to find patients suffering from Eagle jugular syndrome who present normal or short styloid process, but in close proximity to C1. To test this hypothesis, we are developing a novel software to analyze 3-D spatial orientation of styloid process in patient with a previously diagnosed Eagle jugular syndrome compared to healthy controls. Methods We collected cervical computed tomography angiography (CTA) images from 8 patients with EJS confirmed by venous angiography at our institution, and a control group of 7 random patients, homogenous for sex and age. A blind operator created with a dedicated pre-existing software3, an editable 3-D model (.stl file) of the 3 main region of interest (ROI), namely: right styloid, left styloid, C1 anterior arch. Starting from this dataset, our software, written using the open-source package management system Anaconda4 ver. 2-2.4.0, compares all the possible couples of points between each styloid process and the C1 arch, detecting the minimum and maximum distance. Then, it provides the mean spatial orientation of the process respect the CT-axis: x-axis (from left to right), y-axis (from occiput to nose) and z-axis (cranio-caudal). Results By now we included 15 patients (8 cases, 7 controls), homogeneous for sex and age. Preliminary data (Table 1), although not statistically significant yet, seems to indicate that Eagle jugular patients effectively have a more vertical styloid process, meaning an angle between styloid and y-axis greater than controls, rather than a longer one. Conclusions Our preliminary results could confirm that spatial orientation is more important in Eagle jugular patients than styloid process length. This study is currently ongoing and we planned to enroll at least 20 subjects for each arm. At the same time, we are collecting data from patients with carotic variant of Eagle syndrome, to better characterize morphometric structure of styloid in various subset of this pathology.","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131764581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Simka, S. A. Iqrar, A. Rashid, Aiman Rashid, M. Nowak
Background. Currently, pathological jugular valves are thought to be the main cause of altered hemodynamics in the internal jugular veins, the so-called chronic cerebrospinal venous insufficiency. The alternative interpretation of flow disturbances in these veins is that the main source of abnormal outflow are nozzle-like strictures in their upper parts, at the level or just below the jugular foramen, for example, caused by an enlarged transverse process of the atlas and/or styloid process of the temporal bone.1 These in silico studies were aimed at validation of this hypothesis. Methods. With the use of computational fluid mechanics software: the Flowsquare+ and the COMSOL multiphysics, we simulated blood flow in the models of internal jugular veins that exhibited different morphologies (Figure 1). With the Flowsquare+ software, we performed 3-dimensional simulations for the assessment of relevance of the strictures at the level of jugular foramen, while the COMSOL multiphysics software, which was used in 2-dimensional mode, gave us more detailed insight into the behavior of the jugular valve. Results. There was a normal unidirectional flow, with the centrally positioned centerline velocity and no flow separation in modeled veins, which were not narrowed or presented with gradual narrowings. On the contrary, in a majority of models with nozzle-like strictures located at the beginning of the studied veins, abnormal flow patterns were revealed, with significant flow separation and regions with reversed flow. The most severe flow abnormalities were not seen in the models with nozzles of a small cross-sectional area, but rather in those positioned asymmetrically. Abnormal valves (with reversed or asymmetric leaflets) further impaired the flow in models with symmetrically positioned nozzles, but had no significant impact on the flow in a case of an already altered flow evoked by the asymmetric nozzles.1 Importantly, simulations performed with the COMSOL multiphysics revealed that flow disturbances evoked by significant stenosis in the upper part of the internal jugular vein distort leaflets of the jugular valve. This was not seen as a case of a minor stenosis. Conclusions. We demonstrated that our working hypothesis is credible and that impaired outflow from the brain through the internal jugular veins is likely to be primarily caused by pathological strictures in the upper parts of these veins, instead of pathological jugular valves that, as of yet, were the main target of clinical research. In addition, pathology of the jugular valves may be secondary to the strictures in the upper segments of the internal jugular veins.
{"title":"Abnormal jugular valves are not the sole explanation of an impaired outflow from the cranial cavity through the internal jugular veins: results of in silico studies","authors":"M. Simka, S. A. Iqrar, A. Rashid, Aiman Rashid, M. Nowak","doi":"10.4081/vl.2022.10957","DOIUrl":"https://doi.org/10.4081/vl.2022.10957","url":null,"abstract":"Background. Currently, pathological jugular valves are thought to be the main cause of altered hemodynamics in the internal jugular veins, the so-called chronic cerebrospinal venous insufficiency. The alternative interpretation of flow disturbances in these veins is that the main source of abnormal outflow are nozzle-like strictures in their upper parts, at the level or just below the jugular foramen, for example, caused by an enlarged transverse process of the atlas and/or styloid process of the temporal bone.1 These in silico studies were aimed at validation of this hypothesis. \u0000Methods. With the use of computational fluid mechanics software: the Flowsquare+ and the COMSOL multiphysics, we simulated blood flow in the models of internal jugular veins that exhibited different morphologies (Figure 1). With the Flowsquare+ software, we performed 3-dimensional simulations for the assessment of relevance of the strictures at the level of jugular foramen, while the COMSOL multiphysics software, which was used in 2-dimensional mode, gave us more detailed insight into the behavior of the jugular valve. Results. There was a normal unidirectional flow, with the centrally positioned centerline velocity and no flow separation in modeled veins, which were not narrowed or presented with gradual narrowings. On the contrary, in a majority of models with nozzle-like strictures located at the beginning of the studied veins, abnormal flow patterns were revealed, with significant flow separation and regions with reversed flow. The most severe flow abnormalities were not seen in the models with nozzles of a small cross-sectional area, but rather in those positioned asymmetrically. Abnormal valves (with reversed or asymmetric leaflets) further impaired the flow in models with symmetrically positioned nozzles, but had no significant impact on the flow in a case of an already altered flow evoked by the asymmetric nozzles.1 Importantly, simulations performed with the COMSOL multiphysics revealed that flow disturbances evoked by significant stenosis in the upper part of the internal jugular vein distort leaflets of the jugular valve. This was not seen as a case of a minor stenosis. \u0000Conclusions. We demonstrated that our working hypothesis is credible and that impaired outflow from the brain through the internal jugular veins is likely to be primarily caused by pathological strictures in the upper parts of these veins, instead of pathological jugular valves that, as of yet, were the main target of clinical research. In addition, pathology of the jugular valves may be secondary to the strictures in the upper segments of the internal jugular veins.","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128528886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiani Hu, Yimin Shen, Lara M. Fahmy, S. Krishnamurthy, Jie Li, L. Zhang, Yongsheng Chen, M. Haacke, Q. Jiang
Background: Impaired cerebral waste clearance (CWC) has been associated with a broad range of both physiological and pathophysiological neurologic conditions.1,2 Because of the unique anatomy of the brain parenchyma, theoretically, in the brain parenchyma, biochemically inert waste such as magnetic resonance imaging (MRI) contrast agents can only be removed through two possible pathways: cerebrospinal fluid (CSF) pathway, and/or vascular pathway. Despite the controversy, there seems to be a solid consensus on the participation of the CSF pathway in CWC.3 In contrast to the CSF system, the current consensus is that the parenchymal vascular system does not participate in CWC. Considering there is a big difference in flow rate between the blood (2 mL/min) and the CSF (3.7 µL/min) and the brain is the most bioactive, energy-consuming organ (20% nutrition for about 5% of body weight) in the body, it is illogical that the brain would rely on the slow CSF circulation for CWC while less bioactive tissues outside the brain require both the fast vascular and slow lymphatic systems to remove waste in a timely manner.4,5 Methods: Superparamagnetic iron oxide–enhanced susceptibility-weighted imaging (SPIO-SWI) and quantitative susceptibility mapping (QSM) methods were used to simultaneously study 7 T MRI signal changes in parenchymal veins, arteries, and their corresponding para-vascular spaces in 26 rats, following intra-cisterna magna (ICM) infusion of different CSF tracers (FeREX, ferumoxytol, Fe-Dextran) to determine the amount of tracer in the artery and vein quantitatively. Results: The parenchymal venous system participated in CSF tracer clearance following ICM infusion of different MRI tracers with different concentrations of iron. Parenchymal venous participation was more obvious when 75 μg iron was injected. In the parenchymal veins, the relative mean (±SE) value of the susceptibility increased by 13.5±1.0% at 15 min post-tracer infusion (p<0.01), and 33.6±6.7% at 45 min post-tracer infusion (p=0.01), compared to baseline. In contrast to the parenchymal veins, a negligible amount of CSF tracer entered the parenchymal arteries: 1.3±2.6% at 15 min post-tracer infusion (p=0.6), and 12±19% at 45 min post-tracer infusion (p=0.5), compared to baseline. Conclusions: MRI tracers can enter the parenchymal vascular system and more MRI tracers were observed in the cerebral venous than arterial vessels, suggesting the direct participation of parenchymal vascular system in CWC.
{"title":"Quantitative results for the direct participation of the parenchymal vascular system in cerebral waste removal","authors":"Jiani Hu, Yimin Shen, Lara M. Fahmy, S. Krishnamurthy, Jie Li, L. Zhang, Yongsheng Chen, M. Haacke, Q. Jiang","doi":"10.4081/vl.2022.10950","DOIUrl":"https://doi.org/10.4081/vl.2022.10950","url":null,"abstract":"Background: Impaired cerebral waste clearance (CWC) has been associated with a broad range of both physiological and pathophysiological neurologic conditions.1,2 Because of the unique anatomy of the brain parenchyma, theoretically, in the brain parenchyma, biochemically inert waste such as magnetic resonance imaging (MRI) contrast agents can only be removed through two possible pathways: cerebrospinal fluid (CSF) pathway, and/or vascular pathway. Despite the controversy, there seems to be a solid consensus on the participation of the CSF pathway in CWC.3 In contrast to the CSF system, the current consensus is that the parenchymal vascular system does not participate in CWC. Considering there is a big difference in flow rate between the blood (2 mL/min) and the CSF (3.7 µL/min) and the brain is the most bioactive, energy-consuming organ (20% nutrition for about 5% of body weight) in the body, it is illogical that the brain would rely on the slow CSF circulation for CWC while less bioactive tissues outside the brain require both the fast vascular and slow lymphatic systems to remove waste in a timely manner.4,5 \u0000Methods: Superparamagnetic iron oxide–enhanced susceptibility-weighted imaging (SPIO-SWI) and quantitative susceptibility mapping (QSM) methods were used to simultaneously study 7 T MRI signal changes in parenchymal veins, arteries, and their corresponding para-vascular spaces in 26 rats, following intra-cisterna magna (ICM) infusion of different CSF tracers (FeREX, ferumoxytol, Fe-Dextran) to determine the amount of tracer in the artery and vein quantitatively. \u0000Results: The parenchymal venous system participated in CSF tracer clearance following ICM infusion of different MRI tracers with different concentrations of iron. Parenchymal venous participation was more obvious when 75 μg iron was injected. In the parenchymal veins, the relative mean (±SE) value of the susceptibility increased by 13.5±1.0% at 15 min post-tracer infusion (p<0.01), and 33.6±6.7% at 45 min post-tracer infusion (p=0.01), compared to baseline. In contrast to the parenchymal veins, a negligible amount of CSF tracer entered the parenchymal arteries: 1.3±2.6% at 15 min post-tracer infusion (p=0.6), and 12±19% at 45 min post-tracer infusion (p=0.5), compared to baseline. \u0000Conclusions: MRI tracers can enter the parenchymal vascular system and more MRI tracers were observed in the cerebral venous than arterial vessels, suggesting the direct participation of parenchymal vascular system in CWC.","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129841956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUND: There is an urgent need for better detection and understanding of vascular abnormalities at the micro-level, where critical vascular nourishment and cellular metabolic changes occur. This is especially the case for structures such as the midbrain and hippocampus, where both the feeding and draining vessels are quite small. The hippocampus is a complex grey matter structure that plays an important role in spatial and episodic memory. It can be affected by a wide range of pathologies including vascular abnormalities. Being able to monitor vascular changes in normal aging in various hippocampal subfields will allow us to better understand vascular vulnerability across the hippocampus. METHODS: We recently introduced the concept of microvascular in-vivo contrast revealed origins (MICRO) protocol to image micro-cerebral vessels.1-3 MICRO uses ferumoxytol, an ultra-small superparamagnetic iron oxides (USPIO) agent, to induce susceptibility in the arteries and veins; and by imaging with high resolution (0.22×0.44×1 mm3) susceptibility weighted imaging sequence (SWI) at 3 T. Although the increased vascular susceptibility enhances the visibility of small sub-voxel vessels, the accompanying strong signal loss of the large vessels deteriorates the local tissue contrast. Hence, data are collected at different time points during a gradual administration (final concentration = 4 mg/kg) of ferumoxytol. Dynamically acquired SWI data were co-registered and combined (phase gradient-based adaptive combination or SWIPGAC) to reduce the blooming artifacts from large vessels, preserving the small-vessel contrast. RESULTS: The presence of ferumoxytol helped to enhance the microvasculature, something that has previously only been demonstrated in cadaver brain studies. Figure 1 shows the difference between the pre-contrast SWI and SWIPGAC data in visualizing the micro-vasculature across four healthy subjects. The intra-hippocampal and superficial major arteries (obtained through a non-linear subtraction method) and veins (obtained by averaging the T1-shortening map, pre-contrast quantitative susceptibility mapping (QSM) and pre-contrast R2* maps) are used as an overlay in the third column to better visualize the major vessels penetrating and draining the hippocampus. The hippocampal fissure, along with the fimbria, granular cell layer of the dentate gyrus and cornu ammonis layers (except for CA1), showed higher micro-vascular density than the other parts of hippocampus. The CA1 region exhibited a significant correlation with age (R=−0.37, p<0.05, n=37). demonstrating an overall loss of hippocampal vascularity in the normal aging process. Moreover, the vascular density reduction was more prominent than the age correlation with the volume reduction (R=−0.1, p>0.05, n=37) of the CA1 subfield. CONCLUSIONS: With this USPIO-induced increase in susceptibility comes the potential to study the cerebral micro-vasculature using high-resolution SWI. There was a strong
{"title":"In vivo vascular mapping of the human hippocampus using MICRO imaging","authors":"S. Buch, Y. Ge, E. M. E. Mark Haacke","doi":"10.4081/vl.2022.10944","DOIUrl":"https://doi.org/10.4081/vl.2022.10944","url":null,"abstract":"BACKGROUND: There is an urgent need for better detection and understanding of vascular abnormalities at the micro-level, where critical vascular nourishment and cellular metabolic changes occur. This is especially the case for structures such as the midbrain and hippocampus, where both the feeding and draining vessels are quite small. The hippocampus is a complex grey matter structure that plays an important role in spatial and episodic memory. It can be affected by a wide range of pathologies including vascular abnormalities. Being able to monitor vascular changes in normal aging in various hippocampal subfields will allow us to better understand vascular vulnerability across the hippocampus. \u0000METHODS: We recently introduced the concept of microvascular in-vivo contrast revealed origins (MICRO) protocol to image micro-cerebral vessels.1-3 MICRO uses ferumoxytol, an ultra-small superparamagnetic iron oxides (USPIO) agent, to induce susceptibility in the arteries and veins; and by imaging with high resolution (0.22×0.44×1 mm3) susceptibility weighted imaging sequence (SWI) at 3 T. Although the increased vascular susceptibility enhances the visibility of small sub-voxel vessels, the accompanying strong signal loss of the large vessels deteriorates the local tissue contrast. Hence, data are collected at different time points during a gradual administration (final concentration = 4 mg/kg) of ferumoxytol. Dynamically acquired SWI data were co-registered and combined (phase gradient-based adaptive combination or SWIPGAC) to reduce the blooming artifacts from large vessels, preserving the small-vessel contrast. \u0000RESULTS: The presence of ferumoxytol helped to enhance the microvasculature, something that has previously only been demonstrated in cadaver brain studies. Figure 1 shows the difference between the pre-contrast SWI and SWIPGAC data in visualizing the micro-vasculature across four healthy subjects. The intra-hippocampal and superficial major arteries (obtained through a non-linear subtraction method) and veins (obtained by averaging the T1-shortening map, pre-contrast quantitative susceptibility mapping (QSM) and pre-contrast R2* maps) are used as an overlay in the third column to better visualize the major vessels penetrating and draining the hippocampus. The hippocampal fissure, along with the fimbria, granular cell layer of the dentate gyrus and cornu ammonis layers (except for CA1), showed higher micro-vascular density than the other parts of hippocampus. The CA1 region exhibited a significant correlation with age (R=−0.37, p<0.05, n=37). demonstrating an overall loss of hippocampal vascularity in the normal aging process. Moreover, the vascular density reduction was more prominent than the age correlation with the volume reduction (R=−0.1, p>0.05, n=37) of the CA1 subfield. \u0000CONCLUSIONS: With this USPIO-induced increase in susceptibility comes the potential to study the cerebral micro-vasculature using high-resolution SWI. There was a strong","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131341125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Evidence of the benefits of aerobic exercise training (AET) on brain structure, function, and perfusion in older adults is inconclusive. Methods: We conducted two randomized controlled trials (RCT) in sedentary older adults with or without mild cognitive impairment (MCI) to address this question.1-3 The trial’s intervention arm was a progressive moderate-to-vigorous intensity AET, and the active control arm was stretching-and-toning (SAT). Outcome measures included neurocognitive function focused on memory and executive function, global and regional brain volume and cortical thickness measured with structural magnetic resonance imaging (MRI), cerebral blood flow (CBF) and CBF pulsatility measured in the large cerebral arteries (the internal carotid artery, the vertebral artery, and the middle cerebral artery) with 2D duplex ultrasonography and transcranial Doppler, central arterial stiffness measured with arterial applanation tonometry, and cardiorespiratory fitness measured with treadmill peak oxygen consumption (V̇O2peak). The duration of both trials was one year. Results: In both studies, we observed that AET increased V̇O2peak significantly by ∼10% while it did not change with SAT. Cognitive composite scores and domain-specific scores improved in both the AET and SAT groups, although no group differences were observed (likely reflected by cognitive test practice effects). Total brain and hippocampal volume and mean cortical thickness decreased in both groups over one year. Conversely, AET increased CBF, and decreased central arterial stiffness and CBF pulsatility. Increases in V̇O2peak with AET were correlated with increases in CBF and decreases in cerebrovascular resistance (CVR). Further, the improved memory score in the AET group was associated with decreased CVR and central arterial stiffness measured with carotid β-stiffness index. Conclusions: Taken together, these findings demonstrated that one-year moderate-to-vigorous intensity AET increased CBF and decreased central arterial stiffness in older adults with or without MCI. We speculate that improvement in cerebrovascular function with AET may precede its potential effects on brain structure and neurocognitive function in older adults. (The research findings presented herein were supported by the National Institutes of Health R01AG033106 and R01HL102457)
{"title":"Aerobic exercise training reduces central arterial stiffness and improves cerebral blood flow in older adults","authors":"Rong Zhang","doi":"10.4081/vl.2022.10962","DOIUrl":"https://doi.org/10.4081/vl.2022.10962","url":null,"abstract":"Background: Evidence of the benefits of aerobic exercise training (AET) on brain structure, function, and perfusion in older adults is inconclusive. \u0000Methods: We conducted two randomized controlled trials (RCT) in sedentary older adults with or without mild cognitive impairment (MCI) to address this question.1-3 The trial’s intervention arm was a progressive moderate-to-vigorous intensity AET, and the active control arm was stretching-and-toning (SAT). Outcome measures included neurocognitive function focused on memory and executive function, global and regional brain volume and cortical thickness measured with structural magnetic resonance imaging (MRI), cerebral blood flow (CBF) and CBF pulsatility measured in the large cerebral arteries (the internal carotid artery, the vertebral artery, and the middle cerebral artery) with 2D duplex ultrasonography and transcranial Doppler, central arterial stiffness measured with arterial applanation tonometry, and cardiorespiratory fitness measured with treadmill peak oxygen consumption (V̇O2peak). The duration of both trials was one year. \u0000Results: In both studies, we observed that AET increased V̇O2peak significantly by ∼10% while it did not change with SAT. Cognitive composite scores and domain-specific scores improved in both the AET and SAT groups, although no group differences were observed (likely reflected by cognitive test practice effects). Total brain and hippocampal volume and mean cortical thickness decreased in both groups over one year. Conversely, AET increased CBF, and decreased central arterial stiffness and CBF pulsatility. Increases in V̇O2peak with AET were correlated with increases in CBF and decreases in cerebrovascular resistance (CVR). Further, the improved memory score in the AET group was associated with decreased CVR and central arterial stiffness measured with carotid β-stiffness index. \u0000Conclusions: Taken together, these findings demonstrated that one-year moderate-to-vigorous intensity AET increased CBF and decreased central arterial stiffness in older adults with or without MCI. We speculate that improvement in cerebrovascular function with AET may precede its potential effects on brain structure and neurocognitive function in older adults. (The research findings presented herein were supported by the National Institutes of Health R01AG033106 and R01HL102457)","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123851026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah Shaykevich, Russell W. Chan, Chandni Rana, M. Eltaeb, J. P. Little, D. Razansky, Kevin C. Chan, S. Shoham
Background: The glymphatic system is a brain waste clearance system mediated via cerebrospinal fluid (CSF) flow,1 with implications for influence on neurodegenerative diseases.2 Most preclinical glymphatic studies employ fluorescence imaging, which provides higher specificity, but a smaller field-of-view (FOV), or magnetic resonance imaging (MRI), which provides brain-wide FOV, but lower specificity. Functional optoacoustic neuro-tomography3 (FONT) offers a larger FOV compared to classical optical methods, and higher specificity compared to MRI. However, FONT has not yet been applied to probe the glymphatic system. In this study, we used fluorescence and optoacoustic imaging of a near-infrared dye, Janelia Fluor 669 (JF669), to track CSF and multimodal CSF-hemodynamic flows in mice. Methods: After observing strong fluorescence and optoacoustic signatures of JF669 in phantom experiments, we performed a series of in vivo experiments in isoflurane-anesthetized C57BL/6 mice (n=3 fluorescence and n=4 FONT experiments, respectively) (Figure 1A). The lumbar injection was applied to deliver JF669 at a rate of 2 µL/min for 30 minutes. A polyethylene tube was placed intrathecally at the lumbar region (L4-L5). The scalp was removed. Fluorescence or FONT images were obtained every 5 minutes after injection. Results: Fluorescence imaging and FONT probe CSF flow Images (Figure 1B) and time traces (Figure 1C) revealed time-dependent anatomical routes of paravascular influx, including the transport along the olfactory artery (OFA), superior cerebellar artery (SCA), and bilateral middle cerebral artery (MCA). For FONT imaging, since the OFA showed strong fluorescence (Figure 1B), we positioned the ultrasound transducer array at the anterior of the mouse brain with a FOV of 5x5 mm2 (Figure 1A). Standard filtered back-projection reconstruction was applied. Besides the OFA route of the paravascular influx, the dynamic images (Figure 1D) and time-traces (Figure 1E) also revealed time-dependent anatomical routes of CSF-interstitial fluid (ISF) exchange in the olfactory bulb (OFB) and paravascular efflux in the superior sagittal sinus (SSS) and the bilateral inferior cerebral vein (ICV). Next, we studied the aquaporin-4 (AQP4) dependence of glymphatic flow by subcutaneously injecting AQP4 inhibitor TGN020, in addition to the prior procedures. Under fluorescence imaging and FONT, we observed that TGN020 significantly decreased and spatially restricted the spread of JF669 in the brain. FONT spectral unmixing separates CSF and blood We swept the OPO through 680 nm to 750 nm, with 10 nm steps at 10 Hz in the phantom and in each animal. The multispectral reconstructions were unmixed using the known absorption spectra of hemoglobin and the JF669 OA spectrum obtained from the phantom.4 This enabled the separation of blood and JF669 signal (Figure 1D). Conclusions: We characterized anatomical routes of paravascular influx (OFA), CSF-ISF exchange (OFB) and paravascular efflu
{"title":"Optoacoustic imaging of the glymphatic system","authors":"Sarah Shaykevich, Russell W. Chan, Chandni Rana, M. Eltaeb, J. P. Little, D. Razansky, Kevin C. Chan, S. Shoham","doi":"10.4081/vl.2022.10967","DOIUrl":"https://doi.org/10.4081/vl.2022.10967","url":null,"abstract":"Background: The glymphatic system is a brain waste clearance system mediated via cerebrospinal fluid (CSF) flow,1 with implications for influence on neurodegenerative diseases.2 Most preclinical glymphatic studies employ fluorescence imaging, which provides higher specificity, but a smaller field-of-view (FOV), or magnetic resonance imaging (MRI), which provides brain-wide FOV, but lower specificity. Functional optoacoustic neuro-tomography3 (FONT) offers a larger FOV compared to classical optical methods, and higher specificity compared to MRI. However, FONT has not yet been applied to probe the glymphatic system. In this study, we used fluorescence and optoacoustic imaging of a near-infrared dye, Janelia Fluor 669 (JF669), to track CSF and multimodal CSF-hemodynamic flows in mice. \u0000Methods: After observing strong fluorescence and optoacoustic signatures of JF669 in phantom experiments, we performed a series of in vivo experiments in isoflurane-anesthetized C57BL/6 mice (n=3 fluorescence and n=4 FONT experiments, respectively) (Figure 1A). The lumbar injection was applied to deliver JF669 at a rate of 2 µL/min for 30 minutes. A polyethylene tube was placed intrathecally at the lumbar region (L4-L5). The scalp was removed. Fluorescence or FONT images were obtained every 5 minutes after injection. \u0000Results: Fluorescence imaging and FONT probe CSF flow Images (Figure 1B) and time traces (Figure 1C) revealed time-dependent anatomical routes of paravascular influx, including the transport along the olfactory artery (OFA), superior cerebellar artery (SCA), and bilateral middle cerebral artery (MCA). For FONT imaging, since the OFA showed strong fluorescence (Figure 1B), we positioned the ultrasound transducer array at the anterior of the mouse brain with a FOV of 5x5 mm2 (Figure 1A). Standard filtered back-projection reconstruction was applied. Besides the OFA route of the paravascular influx, the dynamic images (Figure 1D) and time-traces (Figure 1E) also revealed time-dependent anatomical routes of CSF-interstitial fluid (ISF) exchange in the olfactory bulb (OFB) and paravascular efflux in the superior sagittal sinus (SSS) and the bilateral inferior cerebral vein (ICV). Next, we studied the aquaporin-4 (AQP4) dependence of glymphatic flow by subcutaneously injecting AQP4 inhibitor TGN020, in addition to the prior procedures. Under fluorescence imaging and FONT, we observed that TGN020 significantly decreased and spatially restricted the spread of JF669 in the brain. FONT spectral unmixing separates CSF and blood We swept the OPO through 680 nm to 750 nm, with 10 nm steps at 10 Hz in the phantom and in each animal. The multispectral reconstructions were unmixed using the known absorption spectra of hemoglobin and the JF669 OA spectrum obtained from the phantom.4 This enabled the separation of blood and JF669 signal (Figure 1D). \u0000Conclusions: We characterized anatomical routes of paravascular influx (OFA), CSF-ISF exchange (OFB) and paravascular efflu","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124603771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain function requires a finely regulated balance between the delivery of nutrients and the clearance of waste products through the blood flow.1 If the blood flow delivery does not match the dynamic requirements for oxygen and glucose imposed by neural activity, brain dysfunction and damage may ensue. The cognitive alterations caused by vascular factors (vascular cognitive impairment, VCI) and neurodegeneration (Alzheimer’s disease, AD) have traditionally been considered mechanistically distinct, but increasing evidence suggests previously unappreciated commonalities.2 Clinical-pathological studies indicate that vascular lesions aggravate the deleterious effects of AD pathology and traditional stroke risk factors, such as hypertension, are also risk factors for AD, suggesting mechanistic overlap. Furthermore, disturbances of cerebral perfusion and/or energy metabolism occur early in the clinical course of AD suggesting a pathogenic role of vascular insufficiency.3 Corroborating this clinical-epidemiological evidence, experimental data indicate that amyloid-beta, a key pathogenic factor in AD, alters the structure and function of cerebral blood vessels and associated cells (neurovascular complex), effects mediated by activation of innate immune cells leading to vascular oxidative stress and inflammation.1 On the other hand, pathological tau suppresses glutamate-dependent production of nitric oxide, which, in turn, dampens the increase in blood flow produced by synaptic activity, but also leads to neuronal network dysfunction and increased excitability.4 Aging and hypertension can also influence the production and clearance of amyloid-beta, promoting amyloid pathology. Furthermore, ApoE4 plays a critical role in the brain’s susceptibility to vascular damage or neurodegeneration.5 Injury to the neurovascular complex alters cerebral blood flow regulation, depletes vascular reserves, and reduces the brain’s repair potential, effects that amplify the brain dysfunction and damage exerted by incident ischemia and coexisting neurodegeneration. These observations, collectively, indicate that vascular alterations are important both in vascular and neurodegenerative dementias, and suggest novel preventive and treatment modalities for these devastating and highly prevalent conditions. Therefore, in the absence of mechanism-based approaches to counteract dementia, targeting cerebrovascular function may offer the opportunity to mitigate the public health impact of one of the most disabling human afflictions.
{"title":"Neurovascular risk factors and dysfunction in aging and dementia","authors":"C. Iadecola","doi":"10.4081/vl.2022.10951","DOIUrl":"https://doi.org/10.4081/vl.2022.10951","url":null,"abstract":"Brain function requires a finely regulated balance between the delivery of nutrients and the clearance of waste products through the blood flow.1 If the blood flow delivery does not match the dynamic requirements for oxygen and glucose imposed by neural activity, brain dysfunction and damage may ensue. The cognitive alterations caused by vascular factors (vascular cognitive impairment, VCI) and neurodegeneration (Alzheimer’s disease, AD) have traditionally been considered mechanistically distinct, but increasing evidence suggests previously unappreciated commonalities.2 Clinical-pathological studies indicate that vascular lesions aggravate the deleterious effects of AD pathology and traditional stroke risk factors, such as hypertension, are also risk factors for AD, suggesting mechanistic overlap. Furthermore, disturbances of cerebral perfusion and/or energy metabolism occur early in the clinical course of AD suggesting a pathogenic role of vascular insufficiency.3 Corroborating this clinical-epidemiological evidence, experimental data indicate that amyloid-beta, a key pathogenic factor in AD, alters the structure and function of cerebral blood vessels and associated cells (neurovascular complex), effects mediated by activation of innate immune cells leading to vascular oxidative stress and inflammation.1 On the other hand, pathological tau suppresses glutamate-dependent production of nitric oxide, which, in turn, dampens the increase in blood flow produced by synaptic activity, but also leads to neuronal network dysfunction and increased excitability.4 Aging and hypertension can also influence the production and clearance of amyloid-beta, promoting amyloid pathology. Furthermore, ApoE4 plays a critical role in the brain’s susceptibility to vascular damage or neurodegeneration.5 Injury to the neurovascular complex alters cerebral blood flow regulation, depletes vascular reserves, and reduces the brain’s repair potential, effects that amplify the brain dysfunction and damage exerted by incident ischemia and coexisting neurodegeneration. These observations, collectively, indicate that vascular alterations are important both in vascular and neurodegenerative dementias, and suggest novel preventive and treatment modalities for these devastating and highly prevalent conditions. Therefore, in the absence of mechanism-based approaches to counteract dementia, targeting cerebrovascular function may offer the opportunity to mitigate the public health impact of one of the most disabling human afflictions.","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"191 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132865577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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