Structural and Vasoactive Factors Influencing Intracerebral Arterioles in Cases of Vascular Dementia and Other Cerebrovascular Disease: A Review

Zhang, Wei Wei; Badonic, T; Höög, Anders; Jiang, Ming; Chun, Kuo; Nie, Jing; Olsson, Yngve; Sourander, Patrick

doi:10.1159/000106714

Cited by 19 publications

(16 citation statements)

References 48 publications

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“…Cerebral blood vessel walls were ET-1-positive, but without differences in intensity of ET-1 immunoreactivity between MS cases and controls. Similar to previous studies, we found that normal astrocytes did not show ET-1 immunoreactivity (14). However, reactive astrocytes in MS plaques stained strongly positive for ET-1.…”

Section: Discussionsupporting

confidence: 91%

“…However, reactive astrocytes in MS plaques stained strongly positive for ET-1. ET-1 produced and released from reactive astrocytes may reach intracerebral arterioles and induce long-lasting vasoconstriction (14). The mechanism responsible for ET-1 up-regulation in reactive astrocytes is speculative, but cytokines that are elevated in MS plaques, including TNF-α and IL-1β (15), can enhance the transcription of ET-1 (16,17).…”

Section: Discussionmentioning

confidence: 99%

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Cerebral hypoperfusion in multiple sclerosis is reversible and mediated by endothelin-1

D’haeseleer

Beelen

Fierens³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

101

104

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Decreased cerebral blood flow (CBF) may contribute to the pathology of multiple sclerosis (MS), but the underlying mechanism is unknown. We investigated whether the potent vasoconstrictor endothelin-1 (ET-1) is involved. We found that, compared with controls, plasma ET-1 levels in patients with MS were significantly elevated in blood drawn from the internal jugular vein and a peripheral vein. The jugular vein/peripheral vein ratio was 1.4 in patients with MS vs. 1.1 in control subjects, suggesting that, in MS, ET-1 is released from the brain to the cerebral circulation. Next, we performed ET-1 immunohistochemistry on postmortem white matter brain samples and found that the likely source of ET-1 release are reactive astrocytes in MS plaques. We then used arterial spin-labeling MRI to noninvasively measure CBF and assess the effect of the administration of the ET-1 antagonist bosentan. CBF was significantly lower in patients with MS than in control subjects and increased to control values after bosentan administration. These data demonstrate that reduced CBF in MS is mediated by ET-1, which is likely released in the cerebral circulation from reactive astrocytes in plaques. Restoring CBF by interfering with the ET-1 system warrants further investigation as a potential new therapeutic target for MS.M ultiple sclerosis (MS) is a poorly understood chronic disorder of the CNS, characterized by focal inflammatory demyelinating lesions and degenerative processes (1). Immune responses play a crucial role in the pathogenesis of focal lesions that constitute the pathological substrate for relapses. However, the underlying mechanism of the progressive degeneration of axons, which is the primary determinant of long-term disability in MS, is not clear (2), and treatment is lacking.A number of studies found that cerebral blood flow (CBF) is globally impaired in early diagnosed relapsing-remitting MS and primary progressive MS, indicating that it is an integral part of the disease that is already present at the time of diagnosis (3-5). Animal studies have shown that chronic hypoperfusion of the brain can lead to neurodegenerative changes, including axonal degeneration (6).The underlying mechanism of reduced CBF in MS is unknown. Plasma levels of the potent vasoconstrictor endothelin-1 (ET-1) (7) were found to be elevated in patients with MS (8), and this was associated with alterations of extraocular blood flow (9). The reason for the increase in ET-1 levels in MS was unclear, and the findings have not received much attention. We hypothesized that ET-1 might play a role in reducing CBF in MS. ResultsInternal Jugular Vein ET-1 Levels. Individuals with critical illness and systemic conditions known to be associated with increased levels of ET-1 were excluded (10). Ten subjects with MS according to the revised McDonald criteria (11) and 10 matched control subjects were included. Patients with MS were autonomously seeking treatment at the department of cardiovascular and thoracic surgery of Onze-Lieve-Vrouw Ziekenhuis Aalst for so-c...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Cerebral hypoperfusion in multiple sclerosis is reversible and mediated by endothelin-1

D’haeseleer

Beelen

Fierens³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

101

104

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“…Moreover, patients with vascular cognitive impairment have high concentrations of MMP-9 in the CSF [335]. Patients with vascular cognitive impairment also have increased levels of endothelin-1 in the white matter, where it is highly expressed by MMP-2 [336,337]; endothelin-1 is a strong vasoconstrictor that may compromise blood flow to the deep white matter [338].…”

Section: A) Vascular Cognitive Impairmentmentioning

confidence: 99%

Metalloproteinases and Metalloproteinase Inhibitors in Age-Related Diseases

Gargiulo¹,

Gamba²,

Poli³

et al. 2014

CPD

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Degradation of the extracellular matrix is an important feature of embryonic development, morphogenesis, angiogenesis, tissue repair and remodeling. It is precisely regulated under physiological conditions, but when dysregulated it becomes a cause of many diseases, including atherosclerosis, osteoarthritis, diabetic vascular complications, and neurodegeneration. Various types of proteinases are implicated in extracellular matrix degradation, but the major enzymes are considered to be metalloproteinases such as matrix metalloproteinases (MMPs) and disintegrin and metalloproteinase domain (ADAMs) that include ADAMs with a thrombospondin domain (ADAMTS).This review discusses involvement of the major metalloproteinases in some age-related chronic diseases, and examines what is currently known about the beneficial effects of their inhibitors, used as new therapeutic strategies for treating or preventing the development and progression of these diseases.

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“…1,[12][13][14][15][16] Little information is available as to the extent of the adventitial fibrosis in BD with respect to the vessel sizes. 17 In addition, there have been inconsistent reports on the medial changes of the medullary arteries, such as hypertrophy, 18 degeneration, and lipohyalinosis, 1,19,20 which might have resulted from caliber differences or from difficulties in defining the media-adventitia border on routine histological staining.In the present study, we performed a quantitative estimation of the vascular cell components of medullary arteries of a defined caliber by using collagen and smooth muscle actin as immunohistochemical markers. The ultrastructural features were further characterized with immunoelectron microscopy.…”

mentioning

confidence: 99%

Vascular Cell Components of the Medullary Arteries in Binswanger’s Disease Brains

Lin

Tomimoto

Akiguchi

et al. 2000

Stroke

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Background and Purpose-It has been hypothesized that fibrohyalinosis of the medullary arteries may cause white matter lesions in Binswanger's disease (BD). However, previous reports have been inconsistent on the pathological alterations of the cellular components, which may vary in terms of vessel sizes. We therefore quantitatively examined vasculopathy in the medullary arteries of a defined caliber in BD brains with a quantitative technique. Methods-A total of 20 brains were examined: 10 from patients with BD and 10 from age-matched nonneurological control patients. The alterations in the vascular cell components were examined with quantitative immunohistochemistry and immunoelectron microscopy for collagen and smooth muscle actin. Results-The nonneurological control patients showed no white matter lesions. In contrast, the patients with BD invariably had marked white matter lesions, as well as fibrohyalinosis of the medullary arteries. The ratio of the area immunolabeled for collagen type I and type IV to the cross-sectional area was 2-fold higher in the BD patients than in the control patients, regardless of the vessel caliber (PϽ0.005). Although the ratio for smooth muscle actin in the BD brains was increased in arteries of Ͻ100 m (PϽ0.0001), there was no corresponding increase in the arteries of Ͼ100 m. However, in the ultrastructure of these vessels, the cell bodies immunolabeled for smooth muscle actin were hypertrophic and segregated from each other by proliferated fibrils. The basal lamina appeared multilayered, and the endothelial cells were swollen. Collagen type I and type IV immunoreactive fibrils also proliferated in the pericapillary space of the BD brains. Conclusions-The proliferation of collagen fibrils in the media and adventitia of the blood vessels in BD brains was not specific to small arteries and arterioles but also occurred in the pericapillary spaces. Pericapillary sclerosis, smooth muscle cell proliferation in the terminal arterioles, and their morphological transformation in the proximal arteries may alter the shear rates and thus cause profound microcirculatory disturbances in BD brains. (Stroke. 2000;31:1838-1842.)Key Words: Binswanger's disease Ⅲ dementia Ⅲ leukoencephalopathy Ⅲ white matter S ubcortical arteriosclerotic encephalopathy, or Binswanger's disease (BD), is characterized pathologically by widespread white matter lesions, multiple lacunae, and fibrohyalinosis of the medullary arteries. [1][2][3][4] There is a longstanding assumption that white matter lesions are pathogenically attributable to changes in the small vessel of the white matter. 5 Because small arteries and arterioles are the main vessels that resist the intraluminal perfusion pressure, especially in hypertension, 6 it is conceivable that fibrohyalinosis in these vessels has an influence on vascular resistance and flow.Although numerous studies have characterized the white matter lesions in BD, which consist of myelin degeneration, gliosis, edema, and necrotic foci, 4,7-11 the vasculopathy associated with thi...

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Structural and Vasoactive Factors Influencing Intracerebral Arterioles in Cases of Vascular Dementia and Other Cerebrovascular Disease: A Review

Cited by 19 publications

References 48 publications

Cerebral hypoperfusion in multiple sclerosis is reversible and mediated by endothelin-1

Cerebral hypoperfusion in multiple sclerosis is reversible and mediated by endothelin-1

Metalloproteinases and Metalloproteinase Inhibitors in Age-Related Diseases

Vascular Cell Components of the Medullary Arteries in Binswanger’s Disease Brains

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