Cerebrospinal fluid influx drives acute ischemic tissue swelling

Science, Journal Year: 2020, Volume and Issue: 367(6483)

Published: Jan. 31, 2020

Spreading edema after stroke The brain is enveloped in a cushion of cerebrospinal fluid (CSF), which normally provides protection and helps to remove metabolic waste. CSF transport has also recently been shown play unexpected roles neurodegeneration sleep. Mestre et al. used multimodal vivo imaging rodents found that, stroke, an abnormally large volume rushes into the brain, causing swelling (see Perspective by Moss Williams). This influx caused constrictions arteries triggered well-known propagating chemical reaction-diffusion wave called spreading depolarization. can thus role stroke. Science , this issue p. eaax7171 ; see 1195

Language: Английский

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The Meningeal Lymphatic System: A New Player in Neurophysiology

Neuron, Journal Year: 2018, Volume and Issue: 100(2), P. 375 - 388

Published: Oct. 1, 2018

Language: Английский

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Fluid transport in the brain

Physiological Reviews, Journal Year: 2021, Volume and Issue: 102(2), P. 1025 - 1151

Published: May 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.

Language: Английский

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Glymphatic System Impairment in Alzheimer’s Disease and Idiopathic Normal Pressure Hydrocephalus

Trends in Molecular Medicine, Journal Year: 2020, Volume and Issue: 26(3), P. 285 - 295

Published: Jan. 18, 2020

Language: Английский

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Blocking meningeal lymphatic drainage aggravates Parkinson’s disease-like pathology in mice overexpressing mutated α-synuclein

Translational Neurodegeneration, Journal Year: 2019, Volume and Issue: 8(1)

Published: March 1, 2019

Abnormal aggregation of brain α-synuclein is a central step in the pathogenesis Parkinson's disease (PD), thus, it reliable to promote clearance prevent and treat PD. Recent studies have revealed an essential role glymphatic system meningeal lymphatic vessels macromolecules, however, their pathophysiological aspects remain elusive.Meningeal drainage 18-week-old A53T mice was blocked via ligating deep cervical lymph nodes. Six weeks later, functions PD-like phenotypes were systemically analyzed.Glymphatic influx cerebrospinal fluid tracer reduced mice, accompanied with perivascular impaired polarization aquaporin 4 expression substantia nigra. Cervical ligation aggravated dysfunction causing more severe accumulation α-synuclein, glial activation, inflammation, dopaminergic neuronal loss motor deficits.The results suggest that may be aggravating factor PD pathology.

Language: Английский

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The Glymphatic System: A Novel Component of Fundamental Neurobiology

Journal of Neuroscience, Journal Year: 2021, Volume and Issue: 41(37), P. 7698 - 7711

Published: Sept. 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.

Language: Английский

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Role of the Blood-Brain Barrier in Central Nervous System Insulin Resistance

Frontiers in Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: June 4, 2019

The blood-brain barrier (BBB) mediates the communication between periphery and central nervous system (CNS). Recently, CNS insulin resistance has been elucidated to play a role in neurodegenerative disease. This stimulated wealth of information on molecular impact brain, particularly improvement cognition. Since BBB regulates transport into brain thus, helps regulate levels, alterations response could resistance. In this review, we summarize effect some cell types that make up BBB, including endothelial cells, neurons, astrocytes, pericytes. We broadly discuss how these changes specific ultimately BBB. also can levels pathological hallmarks Alzheimer's disease, amyloid beta (Aβ) tau within each type. Finally, suggest interventional approaches overcome detrimental effects regards transport.

Language: Английский

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Elimination of substances from the brain parenchyma: efflux via perivascular pathways and via the blood–brain barrier

Fluids and Barriers of the CNS, Journal Year: 2018, Volume and Issue: 15(1)

Published: Oct. 19, 2018

This review considers efflux of substances from brain parenchyma quantified as values clearances (CL, stated in µL g−1 min−1). Total clearance a substance is the sum for all available routes including perivascular pathways and blood–brain barrier. Perivascular contributes to water-soluble substances. Substances leaving via may enter cerebrospinal fluid (CSF) or lymph. These are also involved entry CSF. However, evidence demonstrating net flow inwards along arteries then outwards veins (the glymphatic hypothesis) still lacking. CLperivascular, that routes, has been measured by following fate exogenously applied labelled tracer amounts sucrose, inulin serum albumin, which not metabolized eliminated across With these total CL ≅ 1 have measured. at least partly other i.e. barrier, higher values. crossing barrier do so passive, non-specific means with CLblood-brain ranging < 0.01 > 1000 water CO2. many small solutes predictable their oil/water partition molecular weight. Transporters specific glucose, lactate polar substrates facilitate producing 50. The principal route movement Na+ Cl− ions probably paracellular through tight junctions between endothelial cells ~ 1. There large fluxes amino acids into out but only observed suggesting substantial reuse essential α-ketoacids within brain. Amyloid-β efflux, measurably faster than inulin, primarily leaves this be important amyloid-β reaches arterial walls resulting cerebral amyloid angiopathy.

Language: Английский

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Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid

Nature, Journal Year: 2022, Volume and Issue: 611(7936), P. 585 - 593

Published: Nov. 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.

Language: Английский

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Impaired Glymphatic Transport in Spontaneously Hypertensive Rats

Journal of Neuroscience, Journal Year: 2019, Volume and Issue: 39(32), P. 6365 - 6377

Published: June 17, 2019

The glymphatic system is a brainwide CSF transport that uses the perivascular space for fast inflow of CSF. Arterial pulsations are major driver inflow, and hypertension causes vascular pathologies, such as arterial stiffening alterations, may impede inflow. We used dynamic contrast-enhanced MRI to assess effect on kinetics in male young adult spontaneously hypertensive (SHR) rats compared with age-matched normotensive Wistar-Kyoto (WKY). anesthetized dexmedetomidine/isoflurane infused paramagnetic contrast (Gd-DOTA) into cisterna magna during quantify kinetics. Structural analysis showed cerebroventricular volumes larger brain significantly smaller SHR WKY rats, regardless age. observed ventricular reflux Gd-DOTA only, indicating abnormal flow dynamics secondary innate hydrocephalus. One-tissue compartment revealed impeded both age groups, implying transport, including solute clearance from parenchyma, impaired evolving SHR, an worsens states chronic hypertension. study demonstrates suppression thus offers new insight coexistence concomitant pathologies Alzheimer9s disease. further highlights importance considering distribution tracers system. SIGNIFICANCE STATEMENT contributes removal amyloid β disrupted disease aging. Using rat model hypertension, we measured gross tracked influx efflux rates MRI, showing compromised early advanced stages provides perspective metabolite fluid homeostasis maintaining healthy blood vessels, increasingly pertinent issue aging population part explain link between pathology

Language: Английский

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