Cerebral amyloid angiopathy and Alzheimer disease — one peptide, two pathways

Nature Reviews Neurology, Год журнала: 2019, Номер 16(1), С. 30 - 42

Опубликована: Дек. 11, 2019

Язык: Английский

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Regulation of cerebral blood flow in humans: physiology and clinical implications of autoregulation

Physiological Reviews, Год журнала: 2021, Номер 101(4), С. 1487 - 1559

Опубликована: Март 26, 2021

Brain function critically depends on a close matching between metabolic demands, appropriate delivery of oxygen and nutrients, removal cellular waste. This requires continuous regulation cerebral blood flow (CBF), which can be categorized into four broad topics:

Язык: Английский

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The Brain’s Glymphatic System: Current Controversies

Trends in Neurosciences, Год журнала: 2020, Номер 43(7), С. 458 - 466

Опубликована: Май 15, 2020

The glymphatic concept along with the discovery of meningeal lymphatic vessels have, in recent years, highlighted that fluid is directionally transported within central nervous system (CNS). Imaging studies, as well manipulations transport, point to a key role glymphatic-lymphatic clearance amyloid-β and other proteins. As such, represents new target combating neurodegenerative diseases. Not unexpectedly, introduction plumbing brain has stirred controversies. This opinion article will highlight what we know about brain's transport systems, where experimental data are lacking, still debated.

Язык: Английский

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Revisiting the neurovascular unit

Nature Neuroscience, Год журнала: 2021, Номер 24(9), С. 1198 - 1209

Опубликована: Авг. 5, 2021

Язык: Английский

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Fluid transport in the brain

Physiological Reviews, Год журнала: 2021, Номер 102(2), С. 1025 - 1151

Опубликована: Май 5, 2021

The brain harbors a unique ability to, figuratively speaking, shift its gears. During wakefulness, the is geared fully toward processing information and behaving, while homeostatic functions predominate during sleep. blood-brain barrier establishes stable environment that optimal for neuronal function, yet imposes physiological problem; transcapillary filtration forms extracellular fluid in other organs reduced to minimum brain. Consequently, depends on special [the cerebrospinal (CSF)] flushed into along perivascular spaces created by astrocytic vascular endfeet. We describe this pathway, coined term glymphatic system, based dependency endfeet their adluminal expression of aquaporin-4 water channels facing CSF-filled spaces. Glymphatic clearance potentially harmful metabolic or protein waste products, such as amyloid-β, primarily active sleep, when drivers, cardiac cycle, respiration, slow vasomotion, together efficiently propel CSF inflow periarterial brain's space contains an abundance proteoglycans hyaluronan, which provide low-resistance hydraulic conduit rapidly can expand shrink sleep-wake cycle. system brain, meets requisites maintain homeostasis similar peripheral organs, considering blood-brain-barrier paths formation egress CSF.

Язык: Английский

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The Glymphatic System: A Novel Component of Fundamental Neurobiology

Journal of Neuroscience, Год журнала: 2021, Номер 41(37), С. 7698 - 7711

Опубликована: Сен. 15, 2021

Throughout the body, lymphatic fluid movement supports critical functions including clearance of excess and metabolic waste. The glymphatic system is analog in CNS. As such, plays a key role regulating directional interstitial movement, waste clearance, and, potentially, brain immunity. enables bulk CSF from subarachnoid space along periarterial spaces, where it mixes with within parenchyma before ultimately exiting via perivenous spaces. This review focuses on important questions about structure this system, why needs transport unexplored aspects transport. We provide evidence that astrocytes blood vessels determine shape perivascular space, controlling fluid. Glymphatic has potential to alter local as well global signaling molecules metabolites. also highlight for cross talk among cardiovascular gastrointestinal tract, system. Much remains be studied, but we propose glymphatic/lymphatic acts cornerstone between body.

Язык: Английский

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Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid

Nature, Год журнала: 2022, Номер 611(7936), С. 585 - 593

Опубликована: Ноя. 9, 2022

Macrophages are important players in the maintenance of tissue homeostasis1. Perivascular and leptomeningeal macrophages reside near central nervous system (CNS) parenchyma2, their role CNS physiology has not been sufficiently well studied. Given continuous interaction with cerebrospinal fluid (CSF) strategic positioning, we refer to these cells collectively as parenchymal border (PBMs). Here demonstrate that PBMs regulate CSF flow dynamics. We identify a subpopulation express high levels CD163 LYVE1 (scavenger receptor proteins), closely associated brain arterial tree, show LYVE1+ motion drives flow. Pharmacological or genetic depletion led accumulation extracellular matrix proteins, obstructing access perivascular spaces impairing perfusion clearance. Ageing-associated alterations impairment dynamics were restored after intracisternal injection macrophage colony-stimulating factor. Single-nucleus RNA sequencing data obtained from patients Alzheimer's disease (AD) non-AD individuals point changes phagocytosis, endocytosis interferon-γ signalling on PBMs, pathways corroborated mouse model AD. Collectively, our results new cellular regulators dynamics, which could be targeted pharmacologically alleviate clearance deficits ageing macrophages, termed here shown fluid, implicating this cell population therapeutic targets neurological diseases such Alzheimer's.

Язык: Английский

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The glymphatic system: Current understanding and modeling

iScience, Год журнала: 2022, Номер 25(9), С. 104987 - 104987

Опубликована: Авг. 20, 2022

We review theoretical and numerical models of the glymphatic system, which circulates cerebrospinal fluid interstitial around brain, facilitating solute transport. Models enable hypothesis development predictions transport, with clinical applications including drug delivery, stroke, cardiac arrest, neurodegenerative disorders like Alzheimer's disease. sort existing into broad categories by anatomical function: Perivascular flow, transport in brain parenchyma, interfaces to perivascular spaces, efflux routes, links neuronal activity. Needs opportunities for future work are highlighted wherever possible; new models, expanded novel experiments inform could all have tremendous value advancing field.

Язык: Английский

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The glymphatic hypothesis: the theory and the evidence

Fluids and Barriers of the CNS, Год журнала: 2022, Номер 19(1)

Опубликована: Фев. 3, 2022

Abstract The glymphatic hypothesis proposes a mechanism for extravascular transport into and out of the brain hydrophilic solutes unable to cross blood–brain barrier. It suggests that there is circulation fluid carrying inwards via periarterial routes, through interstitium outwards perivenous routes. This review critically analyses evidence surrounding mechanisms involved in each these stages. There good both influx efflux occur along routes but no principal route outflow perivenous. Furthermore, inflow unlikely be adequate provide would needed account solute efflux. A tenet flow sweeps parenchyma. However, velocity any possible circulatory within too small compared diffusion effective movement. By comparison earlier classical describing proposed entry parenchyma across barrier, movements by diffusion, partly near surfaces carried “preferred routes” including perivascular spaces, white matter tracts subependymal spaces. did not suggest Evidence still incomplete concerning fate leaving brain. large proportion eliminated from go lymph nodes before reaching blood proportions delivered directly or indirectly CSF which then enters are as yet unclear. In addition, understood why how absence AQP4 normally highly expressed on glial endfeet lining reduces rates elimination delivery it remote sites injection. Neither nor adequately explain move into, Features more complete description discussed. All aspects require further study.

Язык: Английский

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Engineered human blood–brain barrier microfluidic model for vascular permeability analyses

Nature Protocols, Год журнала: 2022, Номер 17(1), С. 95 - 128

Опубликована: Янв. 1, 2022

Язык: Английский

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