PDGF-B Is Required for Development of the Glymphatic System

Munk, Anne Sofie Finmann; Wang, Wei; Bèchet, Nicholas B; Eltanahy, Ahmed M.; Cheng, Anne Xiaoan; Sigurðsson, Björn; Benraiss, Abdellatif; Mäe, Maarja Andaloussi; Kress, Benjamin T.; Kelley, Douglas H.; Betsholtz, Christer; Møllgård, Kjeld; Meißner, Anja; Lundgaard, Iben

doi:10.1016/j.celrep.2019.02.050

Cited by 94 publications

(111 citation statements)

References 69 publications

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“…However, it remains enigmatic whether or not AQP4 is solely responsible for this fluid transport or not (Lendahl et al, 2019). Recently, insufficient PDGFB signaling in the Pdgfb ret/ret mice has shown decreased pericyte coverage of the vessels with decreased AQP4 polarization to astrocyte endfeet, which impairs maturation of the glymphatic function (Munk et al, 2019). The focal absence of pericytes correlates with relocation of AQP4 from astrocytic endfeet to the soma of astrocytes (Armulik et al, 2010).…”

Section: Clearance Of Materials From the Brainmentioning

confidence: 99%

Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia

Uemura

Maki

Ihara

et al. 2020

Front. Aging Neurosci.

157

112

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Pericytes are unique, multi-functional mural cells localized at the abluminal side of the perivascular space in microvessels. Originally discovered in 19th century, pericytes had drawn less attention until decades ago mainly due to lack of specific markers. Recently, however, a growing body of evidence has revealed that pericytes play various important roles: development and maintenance of blood-brain barrier (BBB), regulation of the neurovascular system (e.g., vascular stability, vessel formation, cerebral blood flow, etc.), trafficking of inflammatory cells, clearance of toxic waste products from the brain, and acquisition of stem cell-like properties. In the neurovascular unit, pericytes perform these functions through coordinated crosstalk with neighboring cells including endothelial, glial, and neuronal cells. Dysfunction of pericytes contribute to a wide variety of diseases that lead to cognitive impairments such as cerebral small vessel disease (SVD), acute stroke, Alzheimer's disease (AD), and other neurological disorders. For instance, in SVDs, pericyte degeneration leads to microvessel instability and demyelination while in stroke, pericyte constriction after ischemia causes a no-reflow phenomenon in brain capillaries. In AD, which shares some common risk factors with vascular dementia, reduction in pericyte coverage and subsequent microvascular impairments are observed in association with white matter attenuation and contribute to impaired cognition. Pericyte loss causes BBB-breakdown, which stagnates amyloid β clearance and the leakage of neurotoxic molecules into the brain parenchyma. In this review, we first summarize the characteristics of brain microvessel pericytes, and their roles in the central nervous system. Then, we focus on how dysfunctional pericytes contribute to the pathogenesis of vascular cognitive impairment including cerebral 'small vessel' and 'large vessel' diseases, as well as AD. Finally, we discuss therapeutic implications for these disorders by targeting pericytes.

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Section: Clearance Of Materials From the Brainmentioning

confidence: 99%

Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia

Uemura

Maki

Ihara

et al. 2020

Front. Aging Neurosci.

157

112

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“…The role of Aqp4 in glymphatic function is, however, still a matter of discussion. The development of a functional glymphatic system in mice was shown to be correlated with the expression of Aqp4 at the astrocyte endfoot-vascular interface [62], and using several lines of Aqp4deficient mice, glymphatic tracer transport was shown to depend on intact Aqp4 function [63]. It has, however, also been argued that Aqp4 may not be solely responsible for fluid transport, but that diffusion is in fact an important regulator of paravascular flow.…”

Section: Paravascular Flowmentioning

confidence: 99%

“…Do pericytes play a role in the glymphatic system? A recent analysis of pericyte-deficient Pdgfb ret/ret mice shows a defective development and persistence of glymphatic function, suggesting that PDGFB signaling plays an important role in the development of the glymphatic system [62]. It is likely that this role is mediated by pericytes, since the local absence of pericytes in Pdgfb ret/ret mice correlates with relocation of Aqp4 from astrocyte endfeet to the astrocyte cell soma at these sites [20].…”

Section: Paravascular Flowmentioning

confidence: 99%

Emerging links between cerebrovascular and neurodegenerative diseases—a special role for pericytes

2019

Self Cite

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Neurodegenerative and cerebrovascular diseases cause considerable human suffering, and therapy options for these two disease categories are limited or non-existing. It is an emerging notion that neurodegenerative and cerebrovascular diseases are linked in several ways, and in this review, we discuss the current status regarding vascular dysregulation in neurodegenerative disease, and conversely, how cerebrovascular diseases are associated with central nervous system (CNS) degeneration and dysfunction. The emerging links between neurodegenerative and cerebrovascular diseases are reviewed with a particular focus on pericytes-important cells that ensheath the endothelium in the microvasculature and which are pivotal for blood-brain barrier function and cerebral blood flow. Finally, we address how novel molecular and cellular insights into pericytes and other vascular cell types may open new avenues for diagnosis and therapy development for these important diseases.

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“…Van Veluw et al [92] have recently provided evidence on the importance of vasomotion in the clearance of solutes from brain in awake mice. New tools for studying the glymphatic system are welcome and Munk et al [93] have recently identified platelet-derived growth factor-B as being essential for glymphatic development.…”

Section: Csf and Glymphatic Dynamicsmentioning

confidence: 99%

This was the year that was: brain barriers and brain fluid research in 2019

Keep

Jones²,

Drewes

2020

Fluids Barriers CNS

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This editorial highlights advances in brain barrier and brain fluid research published in 2019, as well as addressing current controversies and pressing needs. Topics include recent advances related to: the cerebral endothelium and the neurovascular unit; the choroid plexus, arachnoid membrane; cerebrospinal fluid and the glymphatic hypothesis; the impact of disease states on brain barriers and brain fluids; drug delivery to the brain; and translation of preclinical data to the clinic. This editorial also mourns the loss of two important figures in the field, Malcolm B. Segal and Edward G. Stopa.

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PDGF-B Is Required for Development of the Glymphatic System

Abstract: Highlights d The glymphatic system is first developed in the hippocampus d Insufficient PDGF-B signaling decreases AQP4 polarization to astrocyte vascular endfeet d Insufficient PDGF-B signaling impairs maturation of the glymphatic function

Cited by 94 publications

References 69 publications

Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia

Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia

Emerging links between cerebrovascular and neurodegenerative diseases—a special role for pericytes

This was the year that was: brain barriers and brain fluid research in 2019

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