PDGFRβ Cells Rapidly Relay Inflammatory Signal from the Circulatory System to Neurons via Chemokine CCL2

Duan, Lihui; Zhang, Xiaodi; Miao, Wanying; Sun, Yunjun; Xiong, Guoliang; Wu, Qiu-Zi; Li, Guangying; Yang, Ping; Yu, Hang; Li, Humingzhu; Wang, Yue; Zhang, Min; Hu, Liyuan; Tong, Xiaoping; Zhou, Wenhao; Yu, Xiang

doi:10.1016/j.neuron.2018.08.030

Cited by 150 publications

(152 citation statements)

References 102 publications

(126 reference statements)

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“…Brain pericytes have many properties of immune regulating cells such as (1) responding to and expressing pro-inflammatory and anti-inflammatory molecules, (2) regulating leukocyte extravasation and trafficking, and (3) controlling immune cell activation including T cells, macrophages, and microglia (Rustenhoven et al, 2017;Thomas et al, 2017;Duan et al, 2018;Smyth L.C.D. et al, 2018).…”

Section: Inflammation and The Regulation Of Immune Cellsmentioning

confidence: 99%

“…et al, 2018). In the mouse brain, pericytes function as the initial sensor of systemic inflammation and relay the infection signal to neurons by secreting chemokine CC chemokine ligand 2 (CCL2, also known as monocyte chemotactic protein-1, MCP1) (Duan et al, 2018).…”

Section: Inflammation and The Regulation Of Immune Cellsmentioning

confidence: 99%

“…Activated microglia disrupt the BBB, which triggers angiogenesis (Dudvarski Stankovic et al, 2016;Shigemoto-Mogami et al, 2018). In the mouse brain, pericytes initially respond to the systemic inflammation within 2 h and secrete CCL2 before the response of astrocytes or microglia (Duan et al, 2018). Given that CCL2 is also known to activate microglia Zhang et al, 2017) and microglial process motility dynamics are altered 48 h after systemic infection (Gyoneva et al, 2014), pericytes might modulate microglial process motility and physical dynamics around the vessels in response to infection.…”

Section: Microglia and Pericytesmentioning

confidence: 99%

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Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia

Uemura

Maki

Ihara

et al. 2020

Front. Aging Neurosci.

160

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: Inflammation and The Regulation Of Immune Cellsmentioning

confidence: 99%

Section: Inflammation and The Regulation Of Immune Cellsmentioning

confidence: 99%

Section: Microglia and Pericytesmentioning

confidence: 99%

See 1 more Smart Citation

Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia

Uemura

Maki

Ihara

et al. 2020

Front. Aging Neurosci.

160

112

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“…3a), we hypothesized that the ZIKV-infected cells are pericytes. Pericytes are in direct contact with endothelial cells and continuously communicate with endothelial and other cells via secretory cytokines (38,39). Brain vascular pericytes are responsible for regulating BBB permeability, cerebrospinal blood flow, angiogenesis, clearance of debris, neuroinflammation, and stem cell activity (25)(26)(27).…”

Section: Zikv Infects Pericytes Not Endothelial Cells In the Cpmentioning

confidence: 99%

Zika virus infects pericytes in the choroid plexus and enters the central nervous system through the blood-cerebrospinal fluid barrier

Kim

Hetman

Hattab

et al. 2019

Preprint

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ABSTRACTZika virus (ZIKV) can infect and cause microcephaly and Zika-associated neurological complications in the developing fetal and adult brains. In terms of pathogenesis, a critical question is how ZIKV overcomes the barriers separating the brain from the circulation and gains access to the central nervous system (CNS). Despite the importance of ZIKV pathogenesis, the route ZIKV utilizes to cross CNS barriers remains unclear.Here we show that in mouse models, ZIKV-infected cells initially appeared in the periventricular regions of the brain, including the choroid plexus and the meninges, prior to infection of the cortex. The appearance of ZIKV in cerebrospinal fluid (CSF) preceded infection of the brain parenchyma. We show that ZIKV infects pericytes in the choroid plexus, and that ZIKV infection of pericytes is dependent on AXL receptor tyrosine kinase. Using an in vitro Transwell system, we highlight the possibility of ZIKV to move from the blood side to CSF side, across the choroid plexus epithelial layers, via a nondestructive pathway (e.g., transcytosis). Finally, we demonstrate that brain infection is significantly attenuated by neutralization of the virus in the CSF, indicating that ZIKV in the CSF at the early stage of infection might be responsible for establishing a lethal infection of the brain. Taken together, our results suggest that ZIKV invades the host brain by exploiting the blood-CSF barrier rather than the blood-brain barrier.AUTHOR SUMMARYZika virus invades the human brains and causes Zika-associated neurological complications; however, the mechanism(s) by which Zika virus accesses the central nerves system remain unclear. Understanding of the cellular and molecular mechanisms will shed light on development of novel therapeutic and prophylactic targets for Zika virus and other neurotropic viruses. Here we use in vivo and in vitro models to understand how Zika virus enters the brain. In mouse models, we found that Zika virus infects pericytes in the choroid plexus at very early stages of infection and neutralization of Zika virus in the cerebrospinal fluid significantly attenuate the brain infection. Further we show evidence that Zika virus can cross the epithelial cell layers in the choroid plexus from the blood side. Our research highlights that ZIKV invades the host brain by exploiting the blood-CSF barrier rather than the blood-brain barrier.

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“…One of the most prominent uses of the scRNA-seq technology is the identification of sub-populations of cells present in a sample and comparing such sub-populations across samples [6,7,8,9,10,11,12,13].…”

Section: Introductionmentioning

confidence: 99%

Accurate sub-population detection and mapping across single cell experiments with PopCorn

Wang

Hoinka

Przytycka

2018

Preprint

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The identification of sub-populations of cells present in a sample, and the comparison of such sub-populations across samples are among the most frequently performed analyzes of single cell data. Current tools for these kind of data however fall short in their ability to adequately perform these tasks. We introduce a novel method, PopCorn (single cell sub-Populations Comparison), allowing for the identification of sub-populations of cells present within individual experiments while simultaneously performing sub-populations mapping across these experiments. PopCorn utilizes several novel algorithmic solutions enabling the execution of these tasks with unprecedented precision. As such, PopCorn provides a much needed tool for comparative analysis of populations of single-cells.

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PDGFRβ Cells Rapidly Relay Inflammatory Signal from the Circulatory System to Neurons via Chemokine CCL2

Cited by 150 publications

References 102 publications

Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia

Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia

Zika virus infects pericytes in the choroid plexus and enters the central nervous system through the blood-cerebrospinal fluid barrier

Accurate sub-population detection and mapping across single cell experiments with PopCorn

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