Cerebral vessels in ageing and Alzheimer's disease

Kalaria, Rajesh N.

doi:10.1016/s0163-7258(96)00116-7

Cited by 300 publications

(284 citation statements)

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“…The aging brain, for instance, undergoes dramatic changes involving global volume, synaptic density, oxygen uptake, and microvascular organization [18][19][20][21]. These factors probably affect vascular density and compliance and may contribute to the altered fMRI signal that is observed in older compared to younger adults.…”

Section: Vascular Density and Vascular Compliance Varies Between Braimentioning

confidence: 99%

Hemodynamic scaling of fMRI-BOLD signal: validation of low-frequency spectral amplitude as a scalability factor

Biswal

Kannurpatti²,

Rypma

2007

Magnetic Resonance Imaging

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AbstractfMRI-BOLD signal representing neural activity may be optimized by discriminating MR signal components related to neural activity and those related to intrinsic properties of the cortical vasculature. The objective of this study was to diminish the hemodynamic change independent of neural activity to obtain a scaled fMRI-BOLD response using two factors namely the low frequency spectral amplitude (LFSA) and breath hold amplitude (BHA). Ten subjects (22-38 years of age) were scanned during various task conditions; (a) rest while breathing room air; (b) bilateral finger-tapping breathing room air; (c) rest during a partial inspirational breath hold; and (d) rest during moderate hypercapnia (breathing 5% CO 2 , 20% O 2 , and 75% N 2 ). In all subjects who breathed 5% CO 2 , regions with significant BOLD response during breath hold correlated significantly with the percent signal increase during 5% CO 2 inhalation. Finger tapping-induced responses in the motor cortex were diminished to a similar extent after scaling using either the LFSA or the BHA. Inter and intra-subject variation in the amplitude of the BOLD signal response reduced after hemodynamic scaling using LFSA or BHA. The results validate the hemodynamic amplitude scaling using the LFSA with earlier established BHA. LFSA free from motor task contamination can be used to calibrate the fMRI-BOLD response in lieu of BHA or hypercapnia to minimize intra and inter subject variation arising from vascular anatomy and vasodilative capacity.

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Section: Vascular Density and Vascular Compliance Varies Between Braimentioning

confidence: 99%

Hemodynamic scaling of fMRI-BOLD signal: validation of low-frequency spectral amplitude as a scalability factor

Biswal

Kannurpatti²,

Rypma

2007

Magnetic Resonance Imaging

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“…5,6 Arterial wall thickening, loss of elasticity, and alterations in perivascular innervation are common changes observed in aged cerebral arteries. 5 Pathology-associated alterations observed in brain arteries/arterioles resemble an admix of accelerated vascular aging and disease-specific hallmarks, such as amyloid deposits in Alzheimer's disease. To date, in comparison with the plethora of structural and functional changes documented in CW arteries of human and animal models, only a limited number of differentially expressed proteins have been identified.…”

Section: Introductionmentioning

confidence: 99%

The Proteome of Mouse Cerebral Arteries

Badhwar

Stanimirovic

Hamel

et al. 2014

J Cereb Blood Flow Metab

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The cerebral vasculature ensures proper cerebral function by transporting oxygen, nutrients, and other substances to the brain. Distribution of oxygenated blood throughout the neuroaxis takes place at the level of the circle of Willis (CW). While morphologic and functional alterations in CW arteries and its main branches have been reported in cerebrovascular and neurodegenerative diseases, accompanying changes in protein expression profiles remain largely uncharacterized. In this study, we performed proteomics to compile a novel list of proteins present in mouse CW arteries and its ramifications. Circle of Willis arteries were surgically removed from 6-month-old wild-type mice, proteins extracted and analyzed by two proteomics approaches, gel-free nanoLC-mass spectrometry (MS)/MS and gel-based GelLC-MS/MS, using nanoAcquity UPLC coupled with ESI-LTQ Orbitrap XL. The two approaches helped maximize arterial proteome coverage. Six biologic and two technical replicates were performed. In all, 2,188 proteins with at least 2 unique high-scoring peptides were identified (6,630 proteins total). Proteins were classified according to vasoactivity, blood-brain barrier specificity, tight junction and adhesion molecules, membrane transporters/channels, and extracellular matrix/basal lamina proteins. Furthermore, we compared the identified CW arterial proteome with the published brain microvascular proteome. Our database provides a vital resource for the study of CW cerebral arterial protein expression profiles in health and disease. Keywords: circle of Willis; cerebral artery; cerebral microvessels; proteomics; vascular reactivity INTRODUCTION A healthy cerebral circulation is essential for maintaining brain perfusion and function. 1 In human, oxygenated blood to the brain is delivered by the internal carotid and vertebrobasilar arteries, and is distributed throughout the neuroaxis at the level of the circle of Willis (CW), a ringlike arterial structure located in the subarachnoid space at the base of the brain. The CW is formed by the confluence of the anastomotic branches of the two internal carotid arteries, rostral portion of the vertebrobasilar artery, and the anterior and posterior communicating arteries. 2 The arterial wreath allows for communications between the anterior and posterior circulations providing blood to the forebrain and the hindbrain, respectively, and insures redundancies in the cerebral circulation. 3 The three principal brain arteries arising from the CW are the left and right anterior, middle, and posterior cerebral arteries, cortical branches of which penetrate the brain parenchyma to irrigate the cerebral cortex and deep structures of the brain. 2 In mice, the CW is similarly located along the ventral aspect of the brain extending from the pons-midbrain junction to the anterior cerebrum and involves the same major arteries. 4 Several studies have reported morphologic and protein expression changes in the CW and its surface branches in healthy aging 5 as well as pathologic conditions, such as cereb...

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“…Particularly the brain microvasculature plays a crucial role in maintaining local brain perfusion to meet the dynamic metabolic needs for normal cerebral function [15,34]. The cerebral capillary endothelium is the anatomical basis of the blood-brain barrier (BBB) and isolates the neuropil from the systemic circulation.…”

Section: Introductionmentioning

confidence: 99%

“…Thinning of the endothelium has been reported in rats [2,8], primates [3] and humans [22,31], and could be caused by a general shrinkage of the cytoplasm or a loss of endothelial cells [2,31]. Yet the most consistent age-related change recorded in mammalian cerebral capillaries is thickening of the basement membrane (BM) or basal lamina [3,4,6,8,9,13,15,17,18,32,33]. In contrast to these studies in animals and to reports suggesting increased thickness of the BM in arteries and arterioles in animals and humans [15], it is not entirely clear whether the capillary BM is affected by the aging process in humans.…”

Section: Introductionmentioning

confidence: 99%

Capillary changes in hippocampal CA1 and CA3 areas of the aging rhesus monkey

Keuker

Luiten

Fuchs

2000

Acta Neuropathologica

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Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 13-05-2018Abstract The rhesus monkey is considered a useful animal model for studying human aging, because non-human primates show many of the neurobiological alterations that have been reported in aging humans. Cognitive impairment that accompanies normal aging may, at least partially, originate from capillary changes in the hippocampus, known to be involved in learning and memory. Agerelated effects on the cerebral capillaries in the nonhuman primate hippocampus have not yet been studied. Therefore, we investigated age-related microvascular changes in the hippocampus of the aged non-human primate. We examined by electron microscopy the microvascular ultrastructure in the CA1 and CA3 areas of 14 male rhesus monkeys (Macaca mulatta), ranging from 1 to 31 years of age. The percentages of capillaries showing basement membrane thickening and deposits of collagen in the basement membrane were determined semiquantitatively in 4 young (1-6 years), 6 middle-aged (17-24 years), and 4 aged (29-31 years) monkeys. Aberrations in the basement membrane are few in young subjects (28 ± 6% of capillaries), and occur with increasing frequency during the aging process in rhesus monkeys (aged animals: 71 ± 5% of capillaries). This could be ascribed to an aging-associated increasing number of capillaries showing depositions of collagen fibrils, rather than local thickenings of the basement membrane. The observed changes in microvascular integrity are very similar to those seen in humans, supporting the view of rhesus monkeys as a model for human aging. The slow but steady progression of these changes could be detrimental for an efficient nutrient supply of the neuropil, and might therefore contribute to decreased cognitive functioning during normal aging.

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Cerebral vessels in ageing and Alzheimer's disease

Cited by 300 publications

References 173 publications

Hemodynamic scaling of fMRI-BOLD signal: validation of low-frequency spectral amplitude as a scalability factor

Hemodynamic scaling of fMRI-BOLD signal: validation of low-frequency spectral amplitude as a scalability factor

The Proteome of Mouse Cerebral Arteries

Capillary changes in hippocampal CA1 and CA3 areas of the aging rhesus monkey

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