Cerebral Small Vessel Disease

Joutel, Anne; Faraci, Frank M.

doi:10.1161/strokeaha.113.002878

Cited by 82 publications

(47 citation statements)

References 55 publications

(98 reference statements)

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“…69 There is degeneration of smooth muscle cells with fibrosis of small arteries in the white matter.…”

Section: Pathophysiology Of White-matter Injury In Small Vessel Diseasementioning

confidence: 99%

“…The finding that CBF was reduced in young patients before the occurrence of clinical symptoms indicates that ischemia could be occurring early in the disease course. 69,72 Patients with SVD often have enlargement of the Virchow-Robin perivascular spaces, 73,74 which are associated with amyloid angiopathy, hypertension, and lobar microbleeds. 75,76 At this time, the clinical significance of the dilatation of the perivascular spaces remains to be determined.…”

Section: Pathophysiology Of White-matter Injury In Small Vessel Diseasementioning

confidence: 99%

“…Most animal studies are based on either hypoxic hypoperfusion secondary to bilateral carotid artery occlusion in normotensive rats or SVD secondary to hypertension in the spontaneously hypertensive/stroke prone rat (SHR/SP). 69,116 Bilateral Carotid Artery Occlusion Bilateral carotid artery occlusion (BCAO) produces hypoxic hypoperfusion, which primarily affects the deep white matter. 117 The tissue is assumed to be hypoxic although direct measurements of tissue oxygen levels have not been made.…”

Section: Biochemical Markers In Diagnosis Of Small Vessel Diseasementioning

confidence: 99%

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Consensus statement for diagnosis of subcortical small vessel disease

Rosenberg

Wallin

Wardlaw

et al. 2015

J Cereb Blood Flow Metab

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186

132

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Vascular cognitive impairment (VCI) is the diagnostic term used to describe a heterogeneous group of sporadic and hereditary diseases of the large and small blood vessels. Subcortical small vessel disease (SVD) leads to lacunar infarcts and progressive damage to the white matter. Patients with progressive damage to the white matter, referred to as Binswanger's disease (BD), constitute a spectrum from pure vascular disease to a mixture with neurodegenerative changes. Binswanger's disease patients are a relatively homogeneous subgroup with hypoxic hypoperfusion, lacunar infarcts, and inflammation that act synergistically to disrupt the blood-brain barrier (BBB) and break down myelin. Identification of this subgroup can be facilitated by multimodal disease markers obtained from clinical, cerebrospinal fluid, neuropsychological, and imaging studies. This consensus statement identifies a potential set of biomarkers based on underlying pathologic changes that could facilitate diagnosis and aid patient selection for future collaborative treatment trials.

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“…69 There is degeneration of smooth muscle cells with fibrosis of small arteries in the white matter.…”

Section: Pathophysiology Of White-matter Injury In Small Vessel Diseasementioning

confidence: 99%

Section: Pathophysiology Of White-matter Injury In Small Vessel Diseasementioning

confidence: 99%

Section: Biochemical Markers In Diagnosis Of Small Vessel Diseasementioning

confidence: 99%

See 1 more Smart Citation

Consensus statement for diagnosis of subcortical small vessel disease

Rosenberg

Wallin

Wardlaw

et al. 2015

J Cereb Blood Flow Metab

Self Cite

186

132

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“…This "stovepiping" creates a bottleneck effect that makes the column of brain parenchyma served by a given PA especially vulnerable to insults that affect flow through that PA (7). Thus, perhaps not surprisingly, PAs are major sites of vulnerability during the progression of vascular diseases (8,9), including CADASIL and other sporadic forms of SVD (2,10,11).…”

Section: Significancementioning

confidence: 99%

Potassium channelopathy-like defect underlies early-stage cerebrovascular dysfunction in a genetic model of small vessel disease

Dabertrand

Kroigaard

Bonev

et al. 2015

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

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122

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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by dominant mutations in the NOTCH3 receptor in vascular smooth muscle, is a genetic paradigm of small vessel disease (SVD) of the brain. Recent studies using transgenic (Tg)Notch3 R169C mice, a genetic model of CADASIL, revealed functional defects in cerebral (pial) arteries on the surface of the brain at an early stage of disease progression. Here, using parenchymal arterioles (PAs) from within the brain, we determined the molecular mechanism underlying the early functional deficits associated with this Notch3 mutation. At physiological pressure (40 mmHg), smooth muscle membrane potential depolarization and constriction to pressure (myogenic tone) were blunted in PAs from TgNotch3 R169C mice. This effect was associated with an ∼60% increase in the number of voltage-gated potassium (K V ) channels, which oppose pressure-induced depolarization. Inhibition of K V 1 channels with 4-aminopyridine (4-AP) or treatment with the epidermal growth factor receptor agonist heparin-binding EGF (HB-EGF), which promotes K V 1 channel endocytosis, reduced K V current density and restored myogenic responses in PAs from TgNotch3 R169C mice, whereas pharmacological inhibition of other major vasodilatory influences had no effect. K V 1 currents and myogenic responses were similarly altered in pial arteries from TgNotch3 R169C mice, but not in mesenteric arteries. Interestingly, HB-EGF had no effect on mesenteric arteries, suggesting a possible mechanistic basis for the exclusive cerebrovascular manifestation of CADASIL. Collectively, our results indicate that increasing the number of K V 1 channels in cerebral smooth muscle produces a mutant vascular phenotype akin to a channelopathy in a genetic model of SVD.

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“…Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is the most common monogenic inherited form of degenerative small vessel disease, 40 and genetic animal models have been developed to express it. It is linked to mutations in the NOTCH3 gene and the pathologic change of CADASIL is the pathognomonic accumulation of granular osmiophilic material within the tunica media in the proximity to the vascular smooth muscle cell membranes.…”

Section: Transgenic Mouse Lines For Cerebral Autosomal Dominant Artermentioning

confidence: 99%

Subcortical ischemic vascular disease: Roles of oligodendrocyte function in experimental models of subcortical white-matter injury

Shindo

Liang

Maki

et al. 2015

J Cereb Blood Flow Metab

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Oligodendrocytes are one of the major cell types in cerebral white matter. Under normal conditions, they form myelin sheaths that encircle axons to support fast nerve conduction. Under conditions of cerebral ischemia, oligodendrocytes tend to die, resulting in white-matter dysfunction. Repair of white matter involves the ability of oligodendrocyte precursors to proliferate and mature. However, replacement of lost oligodendrocytes may not be the only mechanism for white-matter recovery. Emerging data now suggest that coordinated signaling between neural, glial, and vascular cells in the entire neurovascular unit may be required. In this mini-review, we discuss how oligodendrocyte lineage cells participate in signaling and crosstalk with other cell types to underlie function and recovery in various experimental models of subcortical white-matter injury.

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Cerebral Small Vessel Disease

Cited by 82 publications

References 55 publications

Consensus statement for diagnosis of subcortical small vessel disease

Consensus statement for diagnosis of subcortical small vessel disease

Potassium channelopathy-like defect underlies early-stage cerebrovascular dysfunction in a genetic model of small vessel disease

Subcortical ischemic vascular disease: Roles of oligodendrocyte function in experimental models of subcortical white-matter injury

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