Shedding of soluble platelet-derived growth factor receptor-β from human brain pericytes

Sagare, Abhay P.; Sweeney, Melanie D.; Makshanoff, Jacob; Zloković, Berislav V.

doi:10.1016/j.neulet.2015.09.025

Cited by 105 publications

(121 citation statements)

References 34 publications

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“…In this technique, leakage of gadolinium contrast agent into the brain enables the regional CNS BBB permeability constant, K trans , to be quantified using the Patlak analysis method 49,65,66 . A study that compared BBB breakdown in the hippocampus in individuals with MCI compared to age-matched controls found that the extent of BBB breakdown was not affected by vascular risk factors 49 , but correlated with increased CSF levels of soluble platelet-derived growth factor receptor-β (PDGFRβ), a marker of pericyte injury 49,67 . BBB breakdown in the hippocampus occurred prior to hippocampal atrophy 49 , which is typically seen early in AD 68,69 , raising the possibility that BBB breakdown might precede neurodegeneration.…”

Section: Neuroimaging Evidence Of Bbb Disruptionmentioning

confidence: 99%

Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders

2018

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The blood–brain barrier (BBB) is a continuous endothelial membrane within brain microvessels that has sealed cell-to-cell contacts, and is sheathed by mural vascular cells and perivascular astrocyte end-feet. The BBB protects neurons from factors present in the systemic circulation, and maintains the highly regulated CNS internal milieu, which is required for proper synaptic and neuronal functioning. BBB disruption allows influx into the brain of neurotoxic blood-derived debris, cells, and microbial pathogens, and is associated with inflammatory and immune responses, which can initiate multiple pathways of neurodegeneration. This Review discusses neuroimaging studies in the living human brain, post-mortem tissue and biomarker studies demonstrating BBB breakdown in Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, multiple sclerosis, HIV-1-associated dementia and chronic traumatic encephalopathy. The pathogenic mechanisms by which BBB breakdown leads to neuronal injury, synaptic dysfunction, loss of neuronal connectivity and neurodegeneration are described. The importance of a healthy BBB for therapeutic drug delivery, and the adverse effects of disease-initiated, pathological BBB breakdown in relation to brain delivery of neuropharmaceuticals are briefly discussed. Finally, future directions, gaps in the field and opportunities to control the course of neurological diseases by targeting BBB are presented.

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Section: Neuroimaging Evidence Of Bbb Disruptionmentioning

confidence: 99%

Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders

2018

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“…Moreover, plasma PDGF-BB levels are increased in AD patients 74 and soluble PDGFRβ (sPDGFRβ) levels, reflecting pericyte injury 75 , are increased in cerebrospinal fluid (CSF) of subjects with mild dementia and transgenic AD and pericyte-deficient murine models 73 , suggesting dysfunction in PDGF-BB/PDGFRβ pathway compared to control subjects and in experimental models.…”

Section: Pericyte-endothelial Signal Transductionmentioning

confidence: 99%

Pericytes of the neurovascular unit: key functions and signaling pathways

Ayyadurai²,

2016

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Pericytes are vascular mural cells embedded in the basement membrane of blood microvessels. They extend their processes along capillaries, pre-capillary arterioles, and post-capillary venules. The central nervous system (CNS) pericytes are uniquely positioned within the neurovascular unit between endothelial cells, astrocytes, and neurons. They integrate, coordinate, and process signals from their neighboring cells to generate diverse functional responses that are critical for CNS functions in health and disease including regulation of the blood-brain barrier permeability, angiogenesis, clearance of toxic metabolites, capillary hemodynamic responses, neuroinflammation, and stem cell activity. Here, we examine the key signaling pathways between pericytes and their neighboring endothelial cells, astrocytes, and neurons that control neurovascular functions. We also review the role of pericytes in different CNS disorders including rare monogenic diseases and complex neurological disorders such as Alzheimer's disease and brain tumors. Finally, we discuss directions for future studies.

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“…Brain capillary pericyte dysfunction results in blood-brain barrier breakdown and contributes to neurological injury (Sagare et al, 2015). PDGFRβ is expressed in the brain by vascular mural cells, brain capillary pericytes and arterial vascular smooth muscle cells, and is a marker for blood-brain barrier disruption (Sagare et al, 2015).…”

Section: Platelet Derived Growth Factor Receptor β (Pdgfrβ)mentioning

confidence: 99%

“…PDGFRβ is expressed in the brain by vascular mural cells, brain capillary pericytes and arterial vascular smooth muscle cells, and is a marker for blood-brain barrier disruption (Sagare et al, 2015). In cultures of human brain pericytes exposed to hypoxia PDGFRβ is a biomarker of pericyte injury (Sagare et al, 2015). Elevated PDGFRβ in biofluids in patients with neurodegenerative disorders likely reflects ongoing pericyte injury and supports its potential to be developed and validated as a biomarker of brain pericyte injury and blood-brain barrier dysfunction (Sagare et al, 2015).…”

Section: Platelet Derived Growth Factor Receptor β (Pdgfrβ)mentioning

confidence: 99%

“…In cultures of human brain pericytes exposed to hypoxia PDGFRβ is a biomarker of pericyte injury (Sagare et al, 2015). Elevated PDGFRβ in biofluids in patients with neurodegenerative disorders likely reflects ongoing pericyte injury and supports its potential to be developed and validated as a biomarker of brain pericyte injury and blood-brain barrier dysfunction (Sagare et al, 2015). Inflammation, induced either by trauma or hypoxia, can induce blood-brain barrier disruption by altering tight junction function leading to paracellular leakage and affecting vesicular processes leading to transcytotic leakage of potential biomarkers (Banks et al, 2015).…”

Section: Platelet Derived Growth Factor Receptor β (Pdgfrβ)mentioning

confidence: 99%

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Blood biomarkers for evaluation of perinatal encephalopathy: state of the art

Graham

Everett

Delpech

et al. 2018

Current Opinion in Pediatrics

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Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter. Increased excitatory amino acids, lipid peroxidation products, and alteration in microRNAs and inflammatory markers are common to both traumatic brain injury and perinatal encephalopathy. The blood-brain barrier is disrupted in both leading to egress of substances normally only found in the central nervous system. Brain exosomes may represent ideal biomarker containers, as RNA and protein transported within the vesicles are protected from enzymatic degradation. Evaluation of fetal or neonatal brain derived exosomes that cross the blood-brain barrier and circulate peripherally has been referred to as the "liquid brain biopsy." A multiplex of serum biomarkers could improve upon the current imprecise methods of identifying fetal and neonatal brain injury such as fetal heart rate abnormalities, meconium, cord gases at delivery, and Apgar scores. Quantitative biomarker measurements of perinatal brain injury and recovery could lead to operative delivery only in the presence of significant fetal risk, triage to appropriate therapy after birth and measure the effectiveness of treatment.

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Shedding of soluble platelet-derived growth factor receptor-β from human brain pericytes

Cited by 105 publications

References 34 publications

Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders

Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders

Pericytes of the neurovascular unit: key functions and signaling pathways

Blood biomarkers for evaluation of perinatal encephalopathy: state of the art

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