Quantification of Afferent Vessels Shows Reduced Brain Vascular Density in Subjects with Leukoaraiosis

Moody, Dixon M.; Thore, Clara R.; Anstrom, John A.; Challa, Venkata R.; Langefeld, Carl D.; Brown, William R.

doi:10.1148/radiol.2333020981

Cited by 161 publications

(106 citation statements)

References 43 publications

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“…As we previously reported [19], LA lesions were associated with a significantly decreased vascular density and that this decrease was especially apparent at the earliest ages examined, i.e., subjects who died between 55 and 60 yrs. The LA lesions had an average 20% decrease in vessel density compared to the DWM in normal subjects.…”

Section: Discussionsupporting

confidence: 74%

“…Both the LA lesion and the DWM in normal subjects contained vessels ranging in size from arteries and arterioles to capillaries ( Figure 1). Figure 2 shows the data points from the 21 subjects in our published study of vessel density in LA [19]. However, the lines through those data points are not the original computer-generated regression lines.…”

Section: Resultsmentioning

confidence: 99%

“…Details on our method of determining vascular density in the brain in the LA study have been previously published [19]. Twelve male and 9 female subjects comprised the study group with an average age of 72.5 years.…”

Section: Methodsmentioning

confidence: 99%

“…In this article we present an updated interpretation of our previously published data [19] on microvascular damage in LA, with a particular focus on capillary loss, not only in LA lesions, but in the normal-appearing white matter, and even the cortex of LA subjects. We also present our findings of capillary loss in the brain white matter in cases of Alzheimer's disease and after whole-brain irradiation for brain tumors.…”

Section: Introductionmentioning

confidence: 99%

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Vascular dementia in leukoaraiosis may be a consequence of capillary loss not only in the lesions, but in normal-appearing white matter and cortex as well

Brown

Moody

Thore

et al. 2007

Journal of the Neurological Sciences

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129

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We investigated capillary density in 12 subjects with leukoaraiosis (LA), in 9 age-matched normal subjects, in 7 cases of Alzheimer's disease (AD), and 4 after whole-brain irradiation for brain tumors. In the LA study (which as been published), autopsy brains were evaluated by MRI. The presence of LA was indicated by confluent or patchy areas of hyperintensity in the deep white matter. We employed a stereology method using computerized image processing and analysis to determine microvascular density. Afferent vessels (arterioles and capillaries, but not veins or venules) were stained for alkaline phosphatase in 100 μm thick celloidin sections. Microvascular density in LA lesions in the deep white matter (2.56%) was significantly lower than in the corresponding deep white matter of normal subjects (3.20%, p = 0.0180). LA subjects demonstrated decreased vascular density at early ages (55 -65 years) when compared to normal subjects. Our findings indicate that LA affects the brain globally, with capillary loss, although the parenchymal damage is found primarily in the deep white matter. In ongoing studies of the deep white matter in AD brains, we found a pattern of decreased vascular density compared to normal, as well as an age-related decline. In the four irradiated brains, we found very low vessel densities, similar to those found in LA, without an additional age-related decline.

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Section: Discussionsupporting

confidence: 74%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Vascular dementia in leukoaraiosis may be a consequence of capillary loss not only in the lesions, but in normal-appearing white matter and cortex as well

Brown

Moody

Thore

et al. 2007

Journal of the Neurological Sciences

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145

129

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“…fields and processed with Image-pro plus 6.3 to automatically outline, highlight, and quantify the stained areas. The percentage of vascularization, as well as the overall distribution of DRD2 and VEGFR2, was estimated by quantifying the area stained by CD31 (endothelial cell marker), DRD2, and VEGFR2 antibodies per area of interest, according to previously described methods (Caulet et al 1992, Moody et al 2004. We initially aimed to evaluate the proliferation index by quantifying the number Ki67 (proliferation marker)-positive cells per total cell number in each area of interest.…”

Section: Morphometric Analysismentioning

confidence: 99%

The effects of ergot and non-ergot-derived dopamine agonists in an experimental mouse model of endometriosis

Delgado-Rosas¹,

Gómez²,

Ferrero³

et al. 2011

Reproduction

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Implantation of a retrogradely shed endometrium during menstruation requires an adequate blood supply, which allows the growth of endometriotic lesions. This suggests that the development of endometriosis can be impaired by inhibiting angiogenesis. The growth of endometriotic foci is impaired by commercial oncological antiangiogenic drugs used to block vascular endothelial growth factor (VEGF) signaling. The dopamine agonist cabergoline (Cb2) inhibits the growth of established endometriosis lesions by exerting antiangiogenic effects through VEGFR2 inactivation. However, the use of ergot-derived Cb2 is associated with an increased incidence of cardiac valve regurgitation. To evaluate the potential usage of non-ergot-derived dopamine agonists for the treatment of human endometriosis, we compared the efficacy of quinagolide with that of Cb2 in preventing angiogenesis and vascularization in a heterologous mouse model of endometriosis. Nude mice whose peritoneum had been implanted with eutopic human endometrial fragments were treated with vehicle, 50 mg/kg per day oral Cb2, or 50 or 200 mg/kg per day quinagolide during a 14-day period. At the end of the treatment period, the implants were excised in order to assess lesion size, cell proliferation, degree of vascularization, and angiogenic gene expression. Neoangiogenesis was inhibited and the size of active endometriotic lesions, cellular proliferation index, and angiogenic gene expression were significantly reduced by both dopamine agonists when compared with the placebo. Given that Cb2 and quinagolide were equally effective in inhibiting angiogenesis and reducing lesion size, these experiments provide the rationale for pilot studies to explore the use of non-ergot-derived dopamine agonists for the treatment of endometriosis in humans.

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

Shao

Chen

et al. 2010

The Anatomical Record

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We, for the first time, investigated the age-related changes of the capillaries in white matter using immunohistochemistry and stereological techniques. Ten young female (7 months) and 10 aged female (27 months) rats were used. The total length, total volume, and total surface area of the capillaries in white matter of aged rats were all significantly lower than those of young rats. The age-related changes of the capillaries in white matter may have important implications for age-related white matter atrophy and age-related cognitive impairments.

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Quantification of Afferent Vessels Shows Reduced Brain Vascular Density in Subjects with Leukoaraiosis

Abstract: Findings of decreased afferent vascular density in the area of LA and outside the lesion indicate that LA is a generalized cerebrovascular disease process rather than one confined to deep WM.

Cited by 161 publications

References 43 publications

Vascular dementia in leukoaraiosis may be a consequence of capillary loss not only in the lesions, but in normal-appearing white matter and cortex as well

Vascular dementia in leukoaraiosis may be a consequence of capillary loss not only in the lesions, but in normal-appearing white matter and cortex as well

The effects of ergot and non-ergot-derived dopamine agonists in an experimental mouse model of endometriosis

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

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