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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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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Gut Microbiota Interact With the Brain Through Systemic Chronic Inflammation: Implications on Neuroinflammation, Neurodegeneration, and Aging

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 7, 2022

It has been noticed in recent years that the unfavorable effects of gut microbiota could exhaust host vigor and life, yet knowledge theory are just beginning to be established. Increasing documentation suggests microbiota–gut–brain axis not only impacts brain cognition psychiatric symptoms but also precipitates neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), multiple sclerosis (MS). How blood–brain barrier (BBB), a machinery protecting central nervous system (CNS) from systemic circulation, allows risky factors derived translocated into seems paradoxical. For unique anatomical, histological, immunological properties underpinning its permeable dynamics, BBB regarded biomarker associated with neural pathogenesis. The permeability mice rats caused by GM dysbiosis raises question how metabolites change causes pathophysiology neuroinflammation neurodegeneration (NF&ND) aging, pivotal multidisciplinary field tightly immune chronic inflammation. If all, microbiota-induced inflammation (GM-SCI) mainly refers excessive mucosal immunity dysregulation, which is often influenced dietary components age, produced at interface intestinal (IB) or exacerbated after IB disruption, initiates various common diseases along dispersal routes, eventually impairs integrity cause NF&ND aging. To illustrate roles affected inflammatory “leaky” resulting their metabolites, we reviewed selected publications, including role barrier, influences on permeability, NF&ND, add depth bridging inflammation, plausible mechanism indispensable for corruption was highlighted; namely, maintenance cues cytokines, may help understand play major

Language: Английский

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The glymphatic system: Current understanding and modeling

iScience, Journal Year: 2022, Volume and Issue: 25(9), P. 104987 - 104987

Published: Aug. 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.

Language: Английский

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Vascular Cognitive Impairment (VCI)

Neurotherapeutics, Journal Year: 2021, Volume and Issue: 19(1), P. 68 - 88

Published: Dec. 22, 2021

Vascular cognitive impairment (VCI) is predominately caused by vascular risk factors and cerebrovascular disease. VCI includes a broad spectrum of disorders, from mild to dementia ischemic or hemorrhagic stroke, alone in combination with neurodegeneration including Alzheimer's disease (AD) AD-related dementia. accounts for at least 20-40% all diagnosis. Growing evidence indicates that pathology the most important contributor dementia, additive synergistic interactions neurodegenerative pathology. The common underlying mechanism chronic age-related dysregulation CBF, although other such as inflammation cardiovascular dysfunction play role. are prevalent if measured midlife they predict later life. Particularly, hypertension, high cholesterol, diabetes, smoking each associated 20 40% increased Control these multimodality strategies an inclusion lifestyle modification promising strategy treatment prevention VCI. In this review, we present recent developments VCI, its mechanisms, diagnostic criteria, neuroimaging correlates, determinants, current intervention We have also summarized relevant literature field

Language: Английский

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Emerging roles for dynamic aquaporin-4 subcellular relocalization in CNS water homeostasis

Brain, Journal Year: 2021, Volume and Issue: 145(1), P. 64 - 75

Published: Sept. 8, 2021

Abstract Aquaporin channels facilitate bidirectional water flow in all cells and tissues. AQP4 is highly expressed astrocytes. In the CNS, it enriched astrocyte endfeet, at synapses, glia limitans, where mediates exchange across blood–spinal cord blood–brain barriers (BSCB/BBB), controls cell volume, extracellular space migration. Perivascular enrichment of BSCB/BBB suggests a role glymphatic function. Recently, we have demonstrated that localization also dynamically regulated subcellular level, affecting membrane permeability. Ageing, cerebrovascular disease, traumatic CNS injury, sleep disruption are established emerging risk factors developing neurodegeneration, animal models each, impairment function associated with changes perivascular localization. oedema caused by passive influx through response to osmotic imbalances. We reducing dynamic relocalization reduces accelerates functional recovery rodent models. Given difficulties pore-blocking inhibitors, targeting opens up new treatment avenues for oedema, neurovascular neurodegenerative diseases, provides framework address fundamental questions about homeostasis health disease.

Language: Английский

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Mental health care for older adults: recent advances and new directions in clinical practice and research

World Psychiatry, Journal Year: 2022, Volume and Issue: 21(3), P. 336 - 363

Published: Sept. 8, 2022

The world's population is aging, bringing about an ever-greater burden of mental disorders in older adults. Given multimorbidities, the health care these people and their family caregivers labor-intensive. At same time, ageism a big problem for people, with without disorders. Positive elements such as resilience, wisdom prosocial behaviors, need to be highlighted promoted, both combat stigma help protect improve positive psychiatry aging not oxymoron, but scientific construct strongly informed by research evidence. We champion broader concept geriatric - one that encompasses well illness. In present paper, we address issues context four are greatest source years lived disability: neurocognitive disorders, major depression, schizophrenia, substance use emphasize implementation multidisciplinary team care, comprehensive assessment, clinical management, intensive outreach, coordination mental, physical social services. also underscore further into moderators mediators treatment response variability. Because optimal adults patient-focused family-centered, call enhancing well-being caregivers. To optimize safety efficacy pharmacotherapy, attention metabolic, cardiovascular neurological tolerability much needed, together development testing medications reduce risk suicide. normal cognitive antidote catalyst change way think per se late-life more specifically. It this provide directions future research.

Language: Английский

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The glymphatic hypothesis: the theory and the evidence

Fluids and Barriers of the CNS, Journal Year: 2022, Volume and Issue: 19(1)

Published: Feb. 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.

Language: Английский

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Cerebral small vessel disease and vascular cognitive impairment: from diagnosis to management

Current Opinion in Neurology, Journal Year: 2021, Volume and Issue: 34(2), P. 246 - 257

Published: Feb. 23, 2021

Purpose of review We present recent developments in the field small vessel disease (SVD)-related vascular cognitive impairment, including pathological mechanisms, updated diagnostic criteria, profile, neuroimaging markers and risk factors. further address available management therapeutic strategies. Recent findings Vascular neurodegenerative pathologies often co-occur share similar The consensus criteria aim to standardize impairment (VCI) diagnosis, relying strongly on profile MRI findings. Aggressive blood pressure control multidomain lifestyle interventions are associated with decreased but disease-modifying treatments still lacking. research has led a better understanding mechanisms leading SVD-related decline, such as blood-brain barrier dysfunction, reduced cerebrovascular reactivity impaired perivascular clearance. Summary SVD is cause VCI substantial morbidity. Tackling cardiovascular factors currently most effective approach prevent decline elderly. Advanced imaging techniques provide tools for early diagnosis may play an important role surrogate endpoints clinical trials. Designing testing remains key priority healthcare.

Language: Английский

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Normal Aging Induces Changes in the Brain and Neurodegeneration Progress: Review of the Structural, Biochemical, Metabolic, Cellular, and Molecular Changes

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: June 30, 2022

Aging is accompanied by many changes in brain and contributes to progressive cognitive decline. In contrast pathological brain, normal aging have relatively mild but important structural, biochemical molecular level. Representatively, associated include atrophy of tissues, alteration neurotransmitters damage accumulation cellular environment. These effects causative link with age which ultimately results Although several evidences were found it not clearly integrated. Figuring out related as the process that everyone goes through, comprehensive understanding may help progress further studies. This review clarifies an asymptotic manner, from a gross level microscopic level, discusses potential approaches seek

Language: Английский

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