A control mechanism for intra-mural peri-arterial drainage via astrocytes: How neuronal activity could improve waste clearance from the brain

Diem, Alexandra K.; Carare, Roxana O.; Weller, Roy O.; Bressloff, Neil W.

doi:10.1371/journal.pone.0205276

Cited by 28 publications

(22 citation statements)

References 34 publications

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“…The macroscopic changes in CSF flow we identified are expected to alter waste clearance, as pulsatile fluid dynamics can increase mixing and diffusion (20,21,36). Neurovascular coupling has been proposed to contribute to clearance (37), but why it would cause higher clearance rates during sleep was not known. Our study suggests slow neural and hemodynamic oscillations as a new possible contributor to this process, in concert with other physiological factors.…”

Section: One Sentence Summarymentioning

confidence: 98%

Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep

Fultz

Bonmassar

Setsompop

et al. 2019

Science

747

767

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Sleep is essential for both cognition and maintenance of healthy brain function. Slow waves in neural activity contribute to memory consolidation, whereas cerebrospinal fluid (CSF) clears metabolic waste products from the brain. Whether these two processes are related is not known. We used accelerated neuroimaging to measure physiological and neural dynamics in the human brain. We discovered a coherent pattern of oscillating electrophysiological, hemodynamic, and CSF dynamics that appears during non–rapid eye movement sleep. Neural slow waves are followed by hemodynamic oscillations, which in turn are coupled to CSF flow. These results demonstrate that the sleeping brain exhibits waves of CSF flow on a macroscopic scale, and these CSF dynamics are interlinked with neural and hemodynamic rhythms.

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Section: One Sentence Summarymentioning

confidence: 98%

Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep

Fultz

Bonmassar

Setsompop

et al. 2019

Science

747

767

View full text Add to dashboard Cite

show abstract

“…Overactivation of the classical RAS may also reduce clearance of Aβ. Intra-mural peri-arterial drainage (IPAD) and para-vascular glymphatic channels have been implicated in the removal of Aβ from the brain [183][184][185]. The functioning of these drainage pathways depends on the polarised expression of aquaporin-4 in astrocytic endfeet [186], which is regulated by pericytes [187].…”

Section: Potential Neurological Consequences Of Increased Classical Rmentioning

confidence: 99%

Cognitive impact of COVID-19: looking beyond the short term

2020

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COVID-19 is primarily a respiratory disease but up to two thirds of hospitalised patients show evidence of central nervous system (CNS) damage, predominantly ischaemic, in some cases haemorrhagic and occasionally encephalitic. It is unclear how much of the ischaemic damage is mediated by direct or inflammatory effects of virus on the CNS vasculature and how much is secondary to extracranial cardiorespiratory disease. Limited data suggest that the causative SARS-CoV-2 virus may enter the CNS via the nasal mucosa and olfactory fibres, or by haematogenous spread, and is capable of infecting endothelial cells, pericytes and probably neurons. Extracranially, SARS-CoV-2 targets endothelial cells and pericytes, causing endothelial cell dysfunction, vascular leakage and immune activation, sometimes leading to disseminated intravascular coagulation. It remains to be confirmed whether endothelial cells and pericytes in the cerebral vasculature are similarly targeted. Several aspects of COVID-19 are likely to impact on cognition. Cerebral white matter is particularly vulnerable to ischaemic damage in COVID-19 and is also critically important for cognitive function. There is accumulating evidence that cerebral hypoperfusion accelerates amyloid-β (Aβ) accumulation and is linked to tau and TDP-43 pathology, and by inducing phosphorylation of α-synuclein at serine-129, ischaemia may also increase the risk of development of Lewy body disease. Current therapies for COVID-19 are understandably focused on supporting respiratory function, preventing thrombosis and reducing immune activation. Since angiotensin-converting enzyme (ACE)-2 is a receptor for SARS-CoV-2, and ACE inhibitors and angiotensin receptor blockers are predicted to increase ACE-2 expression, it was initially feared that their use might exacerbate COVID-19. Recent meta-analyses have instead suggested that these medications are protective. This is perhaps because SARS-CoV-2 entry may deplete ACE-2, tipping the balance towards angiotensin II-ACE-1-mediated classical RAS activation: exacerbating hypoperfusion and promoting inflammation. It may be relevant that APOE ε4 individuals, who seem to be at increased risk of COVID-19, also have lowest ACE-2 activity. COVID-19 is likely to leave an unexpected legacy of long-term neurological complications in a significant number of survivors. Cognitive follow-up of COVID-19 patients will be important, especially in patients who develop cerebrovascular and neurological complications during the acute illness.

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“…In keeping with this hypothesis, it was observed that inhibition of CAs with AAZ reduces CSF secretion by half in rats [85]. However, clearance of brain products is driven by both CSF movements and vascular pulsatility [86,87]. AAZ is clinically used to increase cerebral blood flow and vasoreactivity [88,89].…”

Section: Altered Carbonic Anhydrases Expression and Activity In Nementioning

confidence: 99%

A New Kid on the Block? Carbonic Anhydrases as Possible New Targets in Alzheimer’s Disease

Provensi

Carta

Nocentini

et al. 2019

IJMS

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The increase in the incidence of neurodegenerative diseases, in particular Alzheimer’s Disease (AD), is a consequence of the world′s population aging but unfortunately, existing treatments are only effective at delaying some of the symptoms and for a limited time. Despite huge efforts by both academic researchers and pharmaceutical companies, no disease-modifying drugs have been brought to the market in the last decades. Recently, several studies shed light on Carbonic Anhydrases (CAs, EC 4.2.1.1) as possible new targets for AD treatment. In the present review we summarized preclinical and clinical findings regarding the role of CAs and their inhibitors/activators on cognition, aging and neurodegeneration and we discuss future challenges and opportunities in the field.

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A control mechanism for intra-mural peri-arterial drainage via astrocytes: How neuronal activity could improve waste clearance from the brain

Cited by 28 publications

References 34 publications

Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep

Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep

Cognitive impact of COVID-19: looking beyond the short term

A New Kid on the Block? Carbonic Anhydrases as Possible New Targets in Alzheimer’s Disease

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