Age-related changes in rat brain capillaries

Hicks, Paul B.; Rolsten, C; Brizzee, D.; Samorajski, T.

doi:10.1016/0197-4580(83)90057-x

Cited by 68 publications

(50 citation statements)

References 30 publications

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“…The results of this study suggest that adult-onset, isolated endocrine IGF-1 deficiency is associated with a significant decline in microvascular density both in the hippocampus and the neocortex, mimicking the aging phenotype Sonntag et al 1997;Amenta et al 1995;Bell and Ball 1981;Hicks et al 1983). Our findings, taken together with results of previous studies obtained in mice with developmental liver-specific knockdown of IGF-1 (Lopez-Lopez et al 2004), suggest that circulating level of IGF-1 is a critical regulator of brain capillarity.…”

Section: Discussionmentioning

confidence: 68%

Circulating IGF-1 deficiency exacerbates hypertension-induced microvascular rarefaction in the mouse hippocampus and retrosplenial cortex: implications for cerebromicrovascular and brain aging

Tarantini

Tucsek

Valcarcel‐Ares

et al. 2016

AGE

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Strong epidemiological and experimental evidence indicate that both age and hypertension lead to significant functional and structural impairment of the cerebral microcirculation, predisposing to the development of vascular cognitive impairment (VCI) and Alzheimer's disease. Preclinical studies establish a causal link between cognitive decline and microvascular rarefaction in the hippocampus, an area of brain important for learning and memory. Age-related decline in circulating IGF-1 levels results in functional impairment of the cerebral microvessels; however, the mechanistic role of IGF-1 deficiency in impaired hippocampal microvascularization remains elusive. The present study was designed to characterize the additive/synergistic effects of IGF-1 deficiency and hypertension on microvascular density and expression of genes involved in angiogenesis and microvascular AGE (2016) 38:273-289

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Section: Discussionmentioning

confidence: 68%

Circulating IGF-1 deficiency exacerbates hypertension-induced microvascular rarefaction in the mouse hippocampus and retrosplenial cortex: implications for cerebromicrovascular and brain aging

Tarantini

Tucsek

Valcarcel‐Ares

et al. 2016

AGE

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“…This indicates that thickening of the BM is not an exclusively age-related phenomenon, but a relatively nonspecific change. In rats, the thickness of the microvascular BM has been shown to increase with advancing age in the cerebellum [6] and the frontal cortex [4,8], as well as in the hippocampal dentate gyrus [32] and CA1 area [8,33]. Besides increases in total thickness, several studies report local thickenings of the microvascular BM in brains of humans [13], new world monkeys [9], and rats [12,13].…”

Section: Discussionmentioning

confidence: 99%

“…This functional decline of the barrier is accompanied with agerelated structural alterations in the BBB. 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].…”

Section: Introductionmentioning

confidence: 99%

“…Among experimental animals, the rhesus monkey is the species closest to the human in which it is practical to conduct a full range of neurobiological studies [30]. Few of the abovementioned studies on aging-associated microvascular aberrations were conducted in the rat hippocampal formation [8,10,32,33]. Moreover, the microvascular integrity in the human hippocampal formation during the aging process has not yet been studied extensively.…”

Section: Introductionmentioning

confidence: 99%

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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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“…38,39 Pericytes Pericytes are BBB associated cells. During aging, pericytes show ultrastructural changes such as vesicular and lipofuscin-like inclusions 1,[40][41][42][43] ; an increased size of mitochondria 44 and a foamy transformation. 45 Ueno et al 46 reported on membranous inclusions within the basal lamina or the ECM of the microvessels and suggested the degeneration of pericytes.…”

Section: Extracellular Matrixmentioning

confidence: 99%

Age-associated physiological and pathological changes at the blood–brain barrier: A review

Erdő

Dénès

Lange

2016

J Cereb Blood Flow Metab

345

260

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The age-associated decline of the neurological and cognitive functions becomes more and more serious challenge for the developed countries with the increasing number of aged populations. The morphological and biochemical changes in the aging brain are the subjects of many extended research projects worldwide for a long time. However, the crucial role of the blood-brain barrier (BBB) impairment and disruption in the pathological processes in age-associated neurodegenerative disorders received special attention just for a few years. This article gives an overview on the major elements of the blood-brain barrier and its supporting mechanisms and also on their alterations during development, physiological aging process and age-associated neurodegenerative disorders (Alzheimer's disease, multiple sclerosis, Parkinson's disease, pharmacoresistant epilepsy). Besides the morphological alterations of the cellular elements (endothelial cells, astrocytes, pericytes, microglia, neuronal elements) of the BBB and neurovascular unit, the changes of the barrier at molecular level (tight junction proteins, adheres junction proteins, membrane transporters, basal lamina, extracellular matrix) are also summarized. The recognition of new players and initiators of the process of neurodegeneration at the level of the BBB may offer new avenues for novel therapeutic approaches for the treatment of numerous chronic neurodegenerative disorders currently without effective medication. KeywordsAging, blood-brain barrier, endothelial cells, neurodegenerative disorders, transport systems Structure of the blood-brain barrier (BBB)Homeostasis of the extracellular microenvironment in the neural tissue of the brain as well as its protection against neurotoxic compounds and variations in the composition of the blood are important for normal function of the neurons. It is warranted by a structure formed between blood and brain, which is therefore called the BBB.1 Clear evidence for the existence of this permeability barrier in the brain emerged in 1909 with the demonstration by Edwin Goldman (a South African-German) that a dye injected into the blood stream of a rat stained the whole body -except for the brain and spinal cord. The opposite was also true: injection of the dye into the cerebral ventricles stained the brain and spinal cord but not the rest of the body. 2,3 This occurs because most organs of the body are perfused by capillaries lined with endothelial cells (ECs) that have small pores (fenestrations) to allow for the rapid movement of small molecules into the organ interstitial fluid from the circulation. However, the capillary endothelium of the brain and spinal cord lack these pores because the ECs of brain capillary are connected to each other by continuous tight junctions (TJs), produced by the interaction of several transmembrane proteins that project into and seal the paracellular pathway.3-5 The interaction of these junctional proteins effectively blocks the free diffusion of

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Age-related changes in rat brain capillaries

Cited by 68 publications

References 30 publications

Circulating IGF-1 deficiency exacerbates hypertension-induced microvascular rarefaction in the mouse hippocampus and retrosplenial cortex: implications for cerebromicrovascular and brain aging

Circulating IGF-1 deficiency exacerbates hypertension-induced microvascular rarefaction in the mouse hippocampus and retrosplenial cortex: implications for cerebromicrovascular and brain aging

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

Age-associated physiological and pathological changes at the blood–brain barrier: A review

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