Contributions of blood–brain barrier imaging to neurovascular unit pathophysiology of Alzheimer’s disease and related dementias

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: Feb. 9, 2023

The blood–brain barrier (BBB) plays important roles in the maintenance of brain homeostasis. Its main role includes three kinds functions: (1) to protect central nervous system from blood-borne toxins and pathogens; (2) regulate exchange substances between parenchyma capillaries; (3) clear metabolic waste other neurotoxic compounds into meningeal lymphatics systemic circulation. Physiologically, BBB belongs glymphatic intramural periarterial drainage pathway, both which are involved clearing interstitial solutes such as β-amyloid proteins. Thus, is believed contribute preventing onset progression for Alzheimer’s disease. Measurements function essential toward a better understanding pathophysiology establish novel imaging biomarkers open new avenues interventions disease related dementias. visualization techniques capillary, cerebrospinal, fluid dynamics around neurovascular unit living human brains have been enthusiastically developed. purpose this review summarize recent developments using advanced magnetic resonance technologies relation First, we give an overview relationship dysfunction. Second, provide brief description about principles non-contrast agent-based contrast methodologies. Third, previous studies that reported findings each method individuals with continuum. Fourth, introduce wide range advance our clinical preclinical settings. Finally, discuss challenges suggest future directions clinically useful

Language: Английский

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Mechanisms of cerebrospinal fluid and brain interstitial fluid production

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 183, P. 106159 - 106159

Published: May 19, 2023

Fluid homeostasis is fundamental for brain function with cerebral edema and hydrocephalus both being major neurological conditions. movement from blood into one crucial element in fluid homeostasis. Traditionally it has been thought to occur primarily at the choroid plexus (CP) as cerebrospinal (CSF) secretion due polarized distribution of ion transporters CP epithelium. However, there are currently controversies importance secretion, just how transport occurs that epithelium versus other sites, well direction flow ventricles. The purpose this review evaluate evidence on CSF vasculature differs tissues, e.g., blood-brain barrier may drive flow. It also addresses recent promising data two potential targets modulating Na

Language: Английский

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Four‐dimensional flow MRI for quantitative assessment of cerebrospinal fluid dynamics: Status and opportunities

NMR in Biomedicine, Journal Year: 2023, Volume and Issue: 37(7)

Published: Dec. 20, 2023

Neurological disorders can manifest with altered neurofluid dynamics in different compartments of the central nervous system. These include alterations cerebral blood flow, cerebrospinal fluid (CSF) and tissue biomechanics. Noninvasive quantitative assessment flow motion is feasible phase contrast magnetic resonance imaging (PC MRI). While two-dimensional (2D) PC MRI routinely utilized research clinical settings to assess through a single slice, comprehensive dynamic be limited or impractical. Recently, four-dimensional (4D) (or time-resolved three-dimensional three-directional velocity encoding) has emerged as powerful extension 2D PC, allowing for large volumetric coverage velocities at high spatiotemporal resolution within clinically reasonable scan times. Yet, most 4D studies have focused on imaging. Characterizing CSF (i.e., flow) interest understand normal brain spine physiology, but also study neurological such dysfunctional metabolite waste clearance, where appear play an important role. However, challenged by long T1 time slower compared which result longer times from low flip angles extended motion-sensitive gradients, hindering adoption. In this work, we review state including challenges, novel solutions current ongoing needs, examples applications, discuss outlook future flow.

Language: Английский

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CSF dynamics throughout the ventricular system using 4D flow MRI: associations to arterial pulsatility, ventricular volumes, and age

Fluids and Barriers of the CNS, Journal Year: 2024, Volume and Issue: 21(1)

Published: Aug. 30, 2024

Cerebrospinal fluid (CSF) dynamics are increasingly studied in aging and neurological disorders. Models of CSF-mediated waste clearance suggest that altered CSF could play a role the accumulation toxic CNS, with implications for Alzheimer's disease other proteinopathies. Therefore, approaches enable quantitative volumetric assessment flow velocities be value. In this study we demonstrate feasibility 4D MRI simultaneous throughout ventricular system, evaluate associations to arterial pulsatility, volumes, age.

Language: Английский

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Fluid dynamics in aging-related dementias

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 177, P. 105986 - 105986

Published: Jan. 2, 2023

Recent human and animal model experimental studies revealed novel pathways for fluid movement, immune cell trafficking metabolic waste clearance in CNS. These raise the intriguing possibility that newly discovered pathways, including glymphatic system, lymphatic meningeal vessels skull-brain communication channels, are impaired aging neurovascular neurodegenerative diseases associated with dementia, Alzheimer's disease (AD) AD-related dementia. We provide an overview of dural systems, review current methods approaches used to study flow humans animals, discuss evidence controversies related its role CNS homeostasis under physiological pathophysiological conditions. Non-invasive imaging needed fully understand mechanisms driving movement their roles across lifespan healthy aging-related

Language: Английский

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The Role of the Glymphatic Clearance System in the Mechanisms of the Interactions of the Sleep–Waking Cycle and the Development of Neurodegenerative Processes

Neuroscience and Behavioral Physiology, Journal Year: 2024, Volume and Issue: 54(2), P. 199 - 204

Published: Feb. 1, 2024

Language: Английский

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Utility of cortical tissue analysis in normal pressure hydrocephalus

Cerebral Cortex, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 24, 2024

Abstract Clinical improvement following neurosurgical cerebrospinal fluid shunting for presumed idiopathic normal pressure hydrocephalus is variable. Idiopathic patients may have undetected Alzheimer’s disease-related cortical pathology that confounds diagnosis and clinical outcomes. In this study, we sought to determine the utility of tissue immuno-analysis in predicting outcomes patients. We performed a pooled analysis using systematic review as well new, original patient cohort. Of 2707 screened studies, 3 studies with total 229 were selected inclusion meta-analysis alongside our Pooled statistics new cohort 36 revealed Aβ + significantly more likely exhibit shunt nonresponsiveness than negative pathology. disease -related be at higher risk treatment facing unfavorable shunting. Thus, from living useful diagnostic prognostic adjunct potentially other neurodegenerative conditions affecting cerebral cortex.

Language: Английский

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A synthesized view of the CSF-blood barrier and its surgical implications for aging disorders

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 5, 2025

In this review, we explore the mechanisms of blood-cerebrospinal fluid (CSF) barrier and CSF transport. We briefly review mathematical framework for transport as described by a set well-studied partial differential equations. Moreover, describe major contributors flow through both diffusive convective forces beginning at molecular level extending into macroscopic clinical observations. addition, neurosurgical perspectives in understanding outflow pathways. Finally, discuss implications dysregulation context neurodegenerative diseases rising role perivascular drainage pathways including glymphatics.

Language: Английский

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Brain fog in long COVID limits function and health status, independently of hospital severity and preexisting conditions

Frontiers in Neurology, Journal Year: 2023, Volume and Issue: 14

Published: May 11, 2023

Importance The U.S. government has named post-acute sequelae of COVID-19 (longCOVID) as influential on disability rates. We previously showed that carries a medical/functional burden at 1 year, and age other risk factors severe were not associated with increased longCOVID risk. Long-term brain fog (BF) prevalence, are poorly understood, especially after mild SARS-CoV-2 infection. Methods A retrospective observational cohort study was conducted an urban tertiary-care hospital. Of 1,032 acute survivors from March 3–May 15, 2020, 633 called, 530 responded (59.2 ± 16.3 years, 44.5% female, 51.5% non-White) about BF longCOVID, ED/hospital utilization, perceived health/social network, effort tolerance, disability. Results At approximately 1-year, 31.9% ( n = 169) experienced BF. Acute severity, age, premorbid cardiopulmonary comorbidities did differ between those with/without year. Patients respiratory had 54% higher than without longCOVID. sleep disturbance (63% vs.29% BF, p < 0.0001), shortness breath (46% vs.18%, weakness (49% vs.22%, dysosmia/dysgeusia (12% vs.5%, 0.004), activity limitations 0.001), disability/leave (11% vs.3%, worsened health since (66% vs.30%, 0.001) social isolation (40% vs.29%, 0.02), despite no differences in age. Conclusions relevance year infection, persists third patients. severity is predictive factor. associates independently persistent debility.

Language: Английский

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Biomechanical instability of the brain–CSF interface in hydrocephalus

Brain, Journal Year: 2024, Volume and Issue: 147(10), P. 3274 - 3285

Published: May 27, 2024

Hydrocephalus, characterized by progressive expansion of the CSF-filled ventricles (ventriculomegaly), is most common reason for brain surgery. 'Communicating' (i.e. non-obstructive) hydrocephalus classically attributed to a primary derangement in CSF homeostasis, such as choroid plexus-dependent hypersecretion, impaired cilia-mediated flow currents, or decreased reabsorption via arachnoid granulations other pathways. Emerging data suggest that abnormal biomechanical properties parenchyma are an under-appreciated driver ventriculomegaly multiple forms communicating across lifespan. We discuss recent evidence from human and animal studies suggests neurodevelopment congenital hydrocephalus, neurodegeneration elderly normal pressure and, all age groups, inflammation-related neural injury post-infectious post-haemorrhagic can result loss stiffness viscoelasticity parenchyma. Abnormal biomechanics create barrier alterations at brain-CSF interface pathologically facilitates secondary enlargement ventricles, even low intracranial pressures. This 'brain-centric' paradigm has implications diagnosis, treatment study womb tomb.

Language: Английский

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