Age-related changes in brain microanatomy: Sensitivity to treatment with the dihydropyridine calcium channel blocker darodipine (PY 108-068)

Amenta, Francesco; Cavallotti, Daniela; Soto, Miguel; Mancini, Maurizio; Naves, F.J.; Ja, Vega; Zeng, Yong-Chun

doi:10.1016/0361-9230(94)00210-r

Cited by 25 publications

(25 citation statements)

References 33 publications

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“…In contrast, quantitative analyses of structural parameters in brain capillaries led to controversial data. Increased age-related capillary density attributed to tissue shrinkage in the human neocortex and hippocampus has been reported earlier [61], but more recent animal and human studies challenged these findings [62][63][64][65][66]. Similarly, an age-related increase of capillary diameters and decrease of capillary length has been found in the aging human hippocampus [67] but not in neocortical areas [65,68].…”

Section: Hippocampal Ad-related Pathology After 90 Years: Sparing Of mentioning

confidence: 71%

Morphological substrates of cognitive decline in nonagenarians and centenarians: A new paradigm?

Imhof

Kovari

Gunten

et al. 2007

Journal of the Neurological Sciences

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Section: Hippocampal Ad-related Pathology After 90 Years: Sparing Of mentioning

confidence: 71%

Morphological substrates of cognitive decline in nonagenarians and centenarians: A new paradigm?

Imhof

Kovari

Gunten

et al. 2007

Journal of the Neurological Sciences

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“…Hutchins et al [94] reported a 39% decrease in arterioles penetrating the cortex. Amenta et al [95] found a decrease in capillary numbers (43%) and length (20%). Amenta et al [96] showed decreases in capillary numbers (23%) and length (5%), and increased in intercapillary distance (48%).…”

Section: Age-related Capillary Lossmentioning

confidence: 95%

Review: Cerebral microvascular pathology in ageing and neurodegeneration

Brown

Thore²

2011

Neuropathology Appl Neurobio

647

576

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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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“…In this same investigation, the older rats had comparable capillary reductions in the occipital cortex and other brain areas. Table 2 of this essay lists age-related reductions in CCD from eleven studies in rats and one each in mice and Macaque monkeys [34,45,49,[54][55][56][57][58][59][60][61][62][63].…”

Section: Decreased Cerebral Capillary Density (Tables 2 and 3)mentioning

confidence: 99%

A Therapeutic Approach for Senile Dementias: Neuroangiogenesis

Ambrose

2014

JAD

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Alzheimer's disease (AD) and related senile dementias (SDs) represent a growing medical and economic crisis in this country. Apart from cautioning persons about risk factors, no practical, effective therapy is currently available. Much of the recent research in AD has been based on the amyloid cascade theory. Another approach assumes a vascular basis for SDs. This paper presents evidence from a score of studies that cerebral capillary density (CCD) declines during old age in animals and people as well as in AD. Neuroangiogenic (NAG) factors initiate and maintain capillaries in the brain. Thus a waning level of these factors and the ensuing declining CCD would lead to local areas of reduced oxygen and glucose and result in impaired synaptic and neuronal function. The NAG hypothesis developed here proposes that the age-linked decline in CCD is a terminal condition in SDs, including many cases of AD. This age-linked decline is independent of any other of the various pathologies proposed as causing AD and listed in Table 1. Waning NAG factors would render the SDs a deficiency condition, somewhat like falling androgen levels in aging males. A logical corollary of this hypothesis is that chronic replacement therapy with recombinant forms of NAG factors may arrest the age-linked decline in CCD and prevent further loss of memory and mental deterioration. A transnasal route of therapy seems the most practical one for general use in the large aging populations.

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Age-related changes in brain microanatomy: Sensitivity to treatment with the dihydropyridine calcium channel blocker darodipine (PY 108-068)

Cited by 25 publications

References 33 publications

Morphological substrates of cognitive decline in nonagenarians and centenarians: A new paradigm?

Morphological substrates of cognitive decline in nonagenarians and centenarians: A new paradigm?

Review: Cerebral microvascular pathology in ageing and neurodegeneration

A Therapeutic Approach for Senile Dementias: Neuroangiogenesis

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