Dataset Information

Arterial Pulsations cannot Drive Intramural Periarterial Drainage: Significance for A? Drainage.

ABSTRACT: Alzheimer's Disease (AD) is the most common form of dementia and to date there is no cure or efficient prophylaxis. The cognitive decline correlates with the accumulation of amyloid-? (A?) in the walls of capillaries and arteries. Our group has demonstrated that interstitial fluid and A? are eliminated from the brain along the basement membranes of capillaries and arteries, the intramural periarterial drainage (IPAD) pathway. With advancing age and arteriosclerosis, the stiffness of arterial walls, this pathway fails in its function and A? accumulates in the walls of arteries. In this study we tested the hypothesis that arterial pulsations drive IPAD and that a valve mechanism ensures the net drainage in a direction opposite to that of the blood flow. This hypothesis was tested using a mathematical model of the drainage mechanism. We demonstrate firstly that arterial pulsations are not strong enough to produce drainage velocities comparable to experimental observations. Secondly, we demonstrate that a valve mechanism such as directional permeability of the IPAD pathway is necessary to achieve a net reverse flow. The mathematical simulation results are confirmed by assessing the pattern of IPAD in mice using pulse modulators, showing no significant alteration of IPAD. Our results indicate that forces other than the cardiac pulsations are responsible for efficient IPAD.

SUBMITTER: Diem AK

PROVIDER: S-EPMC5574214 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Arterial Pulsations cannot Drive Intramural Periarterial Drainage: Significance for Aβ Drainage.

Diem Alexandra K AK MacGregor Sharp Matthew M Gatherer Maureen M Bressloff Neil W NW Carare Roxana O RO Richardson Giles G

Frontiers in neuroscience 20170824

Alzheimer's Disease (AD) is the most common form of dementia and to date there is no cure or efficient prophylaxis. The cognitive decline correlates with the accumulation of amyloid-β (Aβ) in the walls of capillaries and arteries. Our group has demonstrated that interstitial fluid and Aβ are eliminated from the brain along the basement membranes of capillaries and arteries, the intramural periarterial drainage (IPAD) pathway. With advancing age and arteriosclerosis, the stiffness o ...[more]

PMID: 28883786

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Project description:BackgroundCerebrospinal fluid (CSF) circulation in the brain has garnered considerable attention in recent times. In contrast, there have been fewer studies focused on the spine, despite the expected importance of CSF circulation in disorders specific to the spine, including syringomyelia. The driving forces that regulate spinal CSF flow are not well defined and are likely to be different to the brain given the anatomical differences and proximity to the heart and lungs. The aims of this study were to determine the effects of heart rate, blood pressure and respiration on the distribution of CSF tracers in the spinal subarachnoid space, as well as into the spinal cord interstitium.MethodsIn Sprague Dawley rats, physiological parameters were manipulated such that the effects of spontaneous breathing (generating alternating positive and negative intrathoracic pressures), mechanical ventilation (positive intrathoracic pressure only), tachy/bradycardia, as well as hyper/hypotension were separately studied. To investigate spinal CSF hydrodynamics, in vivo near-infrared imaging of intracisternally infused indocyanine green was performed. CSF tracer transport was further characterised with in vivo two-photon intravital imaging. Tracer influx at a microscopic level was quantitatively characterised by ex vivo epifluorescence imaging of fluorescent ovalbumin.ResultsCompared to mechanically ventilated controls, spontaneous breathing animals had significantly greater movement of tracer in the subarachnoid space. There was also greater influx into the spinal cord interstitium. Hypertension and tachycardia had no significant effect on spinal subarachnoid spinal CSF tracer flux and exerted less effect than respiration on tracer influx into the spinal cord.ConclusionsIntrathoracic pressure changes that occur over the respiratory cycle, particularly decreased intrathoracic pressures generated during inspiration, have a profound effect on tracer movement after injection into spinal CSF and increase cord parenchymal tracer influx. Arterial pulsations likely drive fluid transport from perivascular spaces into the surrounding interstitium, but their overall impact is less than that of the respiratory cycle on net tracer influx.

Project description:BACKGROUND:Patients with Stanford type B aortic dissections (ADs) are at risk of long-term disease progression and late complications. The aim of this study was to evaluate the natural course and evolution of acute type B AD and intramural hematomas (IMHs) in patients who presented without complications during their initial hospital admission and who were treated with optimal medical management (MM). METHODS:Databases from 2 aortic centers in Europe and the United States were used to identify 136 patients with acute type B AD (n = 92) and acute type B IMH (n = 44) who presented without complications during their index admission and were treated with MM. Computed tomography angiography scans were available at onset (?14 days) and during follow-up for those patients. Relevant data, including evidence of adverse events during follow-up (AE; defined according to current guidelines), were retrieved from medical records and by reviewing computed tomography scan images. Aortic diameters were measured with dedicated 3-dimensional software. RESULTS:The 1-, 2-, and 5-year event-free survival rates of patients with type B AD were 84.3% (95% confidence interval [CI], 74.4-90.6), 75.4% (95% CI, 64.0-83.7), and 62.6% (95% CI, 68.9-73.6), respectively. Corresponding estimates for IMH were 76.5% (95% CI, 57.8-87.8), 76.5% (95% CI, 57.8-87.8), and 68.9% (95% CI, 45.2-83.9), respectively. In patients with type B AD, risk of an AE increased with aortic growth within the first 6 months after onset. A diameter increase of 5 mm in the first half year was associated with a relative risk for AE of 2.29 (95% CI, 1.70-3.09) compared with the median 6 months' growth of 2.4 mm. In approximately 60% of patients with IMH, the abnormality resolved within 12 months and in the patients with nonresolving IMH, risk of an adverse event was greatest in the first year after onset and remained stable thereafter. CONCLUSIONS:More than one third of patients with initially uncomplicated type B AD suffer an AE under MM within 5 years of initial diagnosis. In patients with nonresolving IMH, most adverse events are observed in the first year after onset. In patients with type B AD an early aortic growth is associated with a greater risk of AE.

Dataset Information

Arterial Pulsations cannot Drive Intramural Periarterial Drainage: Significance for A? Drainage.

Publications

Arterial Pulsations cannot Drive Intramural Periarterial Drainage: Significance for <i>A</i>β Drainage.

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