Stereological Investigation of Age‐Related Changes of the Capillaries in White Matter

Shao, Wei; Li, Chen; Chen, Lin; Qiu, Xuan; Zhang, Wei; Huang, Chunxia; Xia, Ling; Kong, Jiming; Tang, Yong

doi:10.1002/ar.21184

Cited by 33 publications

(50 citation statements)

References 42 publications

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“…The greatest loss occurred in the corpus callosum/white matter, which, consistent with previous findings (Klein, et al, 1986), demonstrated the lowest capillary density of all regions irrespective of age. To the best of our knowledge, our report is the first to correlate age-related changes in cerebral angiogenic potential with capillary rarefaction in white matter of other than human brain, and is in strong agreement with the significant loss of white matter capillaries recently described in the aged rat (Shao, et al 2010). Both the density and gene changes noted carry particular clinical relevance as it has been suggested that age-related microvessel dropout in white matter stems from endothelial dysfunction and is causally related to leukoaraiosis (Brown and Thore, 2011) – a term referring to common neuroradiological findings on CT and MR scans (white matter “hyperintensities”) in elderly people and associated with cognitive decline, gait disturbance, urinary incontinence and depression (Zeevi, et al, 2010).…”

Section: 0 Discussionsupporting

confidence: 90%

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Brain regional angiogenic potential at the neurovascular unit during normal aging

Murugesan

Demarest

Madri

et al. 2012

Neurobiology of Aging

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Given strong regional specialization of the brain, cerebral angiogenesis may be regionally modified during normal aging. To test this hypothesis, expression of a broad cadre of angiogenesis-associated genes was assayed at the neurovascular unit (NVU) in discrete brain regions of young vs. aged mice by laser capture microdissection coupled to quantitative real-time PCR. Complementary quantitative capillary density/branching studies were performed as well. Effects of physical exercise were also assayed to determine if age-related trends could be reversed. Additionally, gene response to hypoxia was probed to highlight age-associated weaknesses in adapting to this angiogenic stress. Aging impacted resting expression of angiogenesis-associated genes at the NVU in a region-dependent manner. Physical exercise reversed some of these age-associated gene trends, as well as positively influenced cerebral capillary density/branching in a region-dependent way. Lastly, hypoxia revealed a weaker angiogenic response in aged brain. These results suggest heterogeneous changes in angiogenic capacity of the brain during normal aging, and imply a therapeutic benefit of physical exercise that acts at the level of the NVU.

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Section: 0 Discussionsupporting

confidence: 90%

“…3-D could be a factor as well. Similar to the unbiased stereological analysis of Shao et al, (2010), the confocal 3-D rendering approach used here, in which total capillary length in thick sections was determined, compensated for age-related changes in brain volume.…”

Section: 0 Discussionmentioning

confidence: 99%

Brain regional angiogenic potential at the neurovascular unit during normal aging

Murugesan

Demarest

Madri

et al. 2012

Neurobiology of Aging

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“…In brain white matter, Shao et al . [87] found a decrease in capillary length (19%) and volume (24%). Klein and Michel [88] reported a 33% decline in vascular density.…”

Section: Capillary Growth and Lossmentioning

confidence: 92%

Review: Cerebral microvascular pathology in ageing and neurodegeneration

Brown

Thore²

2011

Neuropathology Appl Neurobio

656

555

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This review of age-related brain microvascular pathologies focuses on topics studied by this laboratory, including anatomy of the blood supply, tortuous vessels, venous collagenosis, capillary remnants, vascular density, and microembolic brain injury. Our studies feature thick sections, large blocks embedded in celloidin, and vascular staining by alkaline phosphatase (AP). This permits study of the vascular network in three dimensions, and the differentiation of afferent from efferent vessels. Current evidence suggests that there is decreased vascular density in aging, Alzheimer’s disease (AD), and leukoaraiosis (LA), and cerebrovascular dysfunction precedes and accompanies cognitive dysfunction and neurodegeneration. A decline in cerebrovascular angiogenesis may inhibit recovery from hypoxia-induced capillary loss. Cerebral blood flow (CBF) is inhibited by tortuous arterioles and deposition of excessive collagen in veins and venules. Misery perfusion due to capillary loss appears to occur before cell loss in LA, and CBF is also reduced in the normal-appearing white matter. Hypoperfusion occurs early in AD, inducing white matter lesions and correlating with dementia. In vascular dementia, cholinergic reductions are correlated with cognitive impairment, and cholinesterase inhibitors have some benefit. Most lipid microemboli from cardiac surgery pass through the brain in a few days, but some remain for weeks. They can cause what appears to be a type of vascular dementia years after surgery. Donepezil has shown some benefit. Emboli, such as clots, cholesterol crystals, and microspheres can be extruded through the walls of cerebral vessels, but there is no evidence yet that lipid emboli undergo such extravasation.

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“…The young adult brain retains the ability to form vessels under hypoxic conditions, but this capacity is lost in mature and aged brains (Shao et al, 2010;Sonnotag et al, 1997;Harb et al, 2013). During early embryogenesis, vessels in the pia mater invade the brain and converge centripetally toward the ventricles.…”

Section: Changes In the Microvascular Density In The Brain During Lifementioning

confidence: 97%

Microcirculation of the brain: morphological assessment in degenerative diseases and restoration processes

Kolinko¹,

Krakorova

Cendelín³

et al. 2015

Reviews in the Neurosciences

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AbstractBrain microcirculation plays an important role in the pathogenesis of various brain diseases. Several specific features of the circulation in the brain and its functions deserve special attention. The brain is extremely sensitive to hypoxia, and brain edema is more dangerous than edema in other tissues. Brain vessels are part of the blood-brain barrier, which prevents the penetration of some of the substances in the blood into the brain tissue. Herein, we review the processes of angiogenesis and the changes that occur in the brain microcirculation in the most prevalent neurodegenerative diseases. There are no uniform vascular changes in the neurodegenerative diseases. In some cases, the vascular changes are secondary consequences of the pathological process, but they could also be involved in the pathogenesis of the primary disease and contribute to the degeneration of neurons, based on their quantitative characteristics. Additionally, we described the stereological methods that are most commonly used for generating qualitative and quantitative data to assess changes in the microvascular bed of the brain.

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Stereological Investigation of Age‐Related Changes of the Capillaries in White Matter

Cited by 33 publications

References 42 publications

Brain regional angiogenic potential at the neurovascular unit during normal aging

Brain regional angiogenic potential at the neurovascular unit during normal aging

Review: Cerebral microvascular pathology in ageing and neurodegeneration

Microcirculation of the brain: morphological assessment in degenerative diseases and restoration processes

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