Translational value of choroid plexus imaging for tracking neuroinflammation in mice and humans

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(36)

Published: Sept. 3, 2021

Neuroinflammation is a pathophysiological hallmark of multiple sclerosis and has close mechanistic link to neurodegeneration. Although this potentially targetable, robust translatable models reliably quantify track neuroinflammation in both mice humans are lacking. The choroid plexus (ChP) plays pivotal role regulating the trafficking immune cells from brain parenchyma into cerebrospinal fluid (CSF) recently attracted attention as key structure initiation inflammatory responses. In translational framework, we here address integrity multidimensional characteristics ChP under conditions question whether volumes could act an interspecies marker that closely interrelates with functional impairment. Therefore, explore patients two experimental mouse models, cuprizone diet-related demyelination autoimmune encephalomyelitis. We demonstrate enlargement-reconstructed MRI-is highly associated acute disease activity, studied humans. A dependency molecular signatures shown performed transcriptomic analyses. Moreover, pharmacological modulation blood-CSF barrier natalizumab prevents increase volume. enlargement strongly linked emerging impairment depicted patients. Our findings identify hallmarks ongoing neuroinflammatory activity serve promising for reverse-translational approaches.

Language: Английский

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Choroid plexus function in neurological homeostasis and disorders: The awakening of the circadian clocks and orexins

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2022, Volume and Issue: 42(7), P. 1163 - 1175

Published: March 17, 2022

As research regarding the role of circadian rhythms, sleep, and orexinergic system in neurodegenerative diseases is growing, it surprising that choroid plexus (CP) remains underappreciated this realm. Despite its extensive regulation rhythms signalling, as well acting primary conduit between cerebrospinal fluid (CSF) circulatory system, providing a mechanism by which toxic waste molecules can be removed from brain, CP has been largely unexplored neurodegeneration. In review, we explore maintaining brain homeostasis regulating CSF dynamics, how these functions change across lifespan, development to senescence. addition, examine relationship CP, glymphatic highlighting gaps literature areas require immediate exploration. Finally, assess current knowledge, including possible therapeutic strategies, neurological disorders, such traumatic injury, migraine, Alzheimer’s disease, multiple sclerosis.

Language: Английский

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Choroid Plexus Aquaporins in CSF Homeostasis and the Glymphatic System: Their Relevance for Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(1), P. 878 - 878

Published: Jan. 3, 2023

The glymphatic system, a fluid-clearance pathway involved in brain waste clearance, is known to be impaired neurological disorders, including Alzheimer’s disease (AD). For this reason, it important understand the specific mechanisms and factors controlling function. This enables flow of cerebrospinal fluid (CSF) into subsequently interstitium, supported by aquaporins (AQPs). Continuous CSF transport through parenchyma critical for effective drainage solutes, such as toxic proteins, system. However, balance between production secretion from choroid plexus, AQP regulation, also needed. Thus, any condition that affects homeostasis will interfere with removal clearance subsequent processes neurodegeneration. In review, we highlight role AQPs plexus modulation and, consequently, pathway, special focus on AD.

Language: Английский

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Enlarged choroid plexus related to iron rim lesions and deep gray matter atrophy in relapsing-remitting multiple sclerosis

Multiple Sclerosis and Related Disorders, Journal Year: 2023, Volume and Issue: 75, P. 104740 - 104740

Published: April 28, 2023

Language: Английский

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Improving Choroid Plexus Segmentation in the Healthy and Diseased Brain: Relevance for Tau-PET Imaging in Dementia

Journal of Alzheimer s Disease, Journal Year: 2020, Volume and Issue: 74(4), P. 1057 - 1068

Published: March 2, 2020

Recent studies have revealed the possible role of choroid plexus (ChP) in Alzheimer’s disease (AD). T1-weighted MRI is modality choice for segmentation ChP humans. Manual considered gold-standard technique, but given its time-consuming nature, large-scale neuroimaging would be impossible. In this study, we introduce a lightweight algorithm based on Gaussian Mixture Model (GMM). We compared performance against manual as well automated by Freesurfer three separate datasets: 1) patients with structural MRIs enhanced contrast ( n = 19), 2) young healthy subjects 20), and 3) AD 20). GMM outperformed showed high similarity segmentation. To further assess algorithm’s large scale studies, performed segmentations from Human Connectome Project 1,067), controls, mild cognitive impairment (MCI), Disease Neuroimaging Initiative 509). both datasets, segmented more accurately than Freesurfer. show clinical importance accurate segmentation, total AV1451 (tau) PET binding to was measured 108 MCI 32 patients. able reveal higher MCI. Our results provide evidence utility segmenting relevance AD. Future functional will benefit GMM’s

Language: Английский

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Inflammation‐Triggered Enlargement of Choroid Plexus in Subacute COVID‐19 Patients with Neurological Symptoms

Annals of Neurology, Journal Year: 2024, Volume and Issue: 96(4), P. 715 - 725

Published: June 27, 2024

Objective To investigate whether choroid plexus volumes in subacute coronavirus disease 2019 (COVID‐19) patients with neurological symptoms could indicate inflammatory activation or barrier dysfunction and assess their association clinical data. Methods Choroid were measured 28 COVID‐19 via cerebral magnetic resonance imaging (MRI), compared those infection‐triggered non‐COVID‐19 encephalopathy (n = 25), asymptomatic individuals after 21), healthy controls 21). Associations serum markers (peak counts of leukocytes, C‐reactive protein [CRP], interleukin 6), an MRI‐based marker (CSF volume fraction [V‐CSF]), parameters like olfactory performance cognitive scores (Montreal Cognitive Assessment) investigated. Results showed significantly larger than control groups ( p < 0.001, η 2 0.172). These correlated peak leukocyte levels Pearson's r 0.621) V‐CSF 0.009, Spearman's rho 0.534), but neither CRP nor 6. No significant correlations found parameters. Interpretation In COVID‐19, is a central nervous system inflammation the presence neurologic symptoms. The absence enlargement suggests specific severe acute respiratory syndrome effect. This study also documents increase for first time as parainfectious event. ANN NEUROL 2024;96:715–725

Language: Английский

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Choroid plexus volume is enlarged in long COVID and associated with cognitive and brain changes

Molecular Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Language: Английский

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Age-Related Differences in the Choroid Plexus Structural Integrity Are Associated with Changes in Cognition

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

The choroid plexus (CP) plays a critical role in maintaining central nervous system (CNS) homeostasis, producing cerebrospinal fluid, and regulating the entry of specific substances into CNS from blood. CP dysfunction has been implicated various neurological psychiatric disorders, including Alzheimer's disease, Parkinson's multiple sclerosis. This study investigates relationship between structural integrity cognitive decline normative aging, using advanced magnetic resonance imaging techniques, volume, diffusion tensor indices (mean diffusivity, MD, fractional anisotropy, FA) relaxometry metrics (longitudinal, T 1 , transverse, 2 relaxation times). Our results show that diminished microstructural integrity, as reflected by higher MD values, or lower FA is associated with performance processing speed fluency. Notably, measures demonstrated greater sensitivity to than macrostructural measures, i.e. volume. Longitudinal analysis revealed individuals reduced exhibit steeper over time. Furthermore, equation modeling latent variable representing predicts faster overall decline, an effect size comparable age. These findings highlight importance health suggest holistic approach assessing could serve sensitive biomarker for early detection decline. Further research needed elucidate mechanisms underlying explore potential therapeutic implications targeting function prevent treat age-related deficits.

Language: Английский

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The Lactate Receptor HCA1 Is Present in the Choroid Plexus, the Tela Choroidea, and the Neuroepithelial Lining of the Dorsal Part of the Third Ventricle

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(18), P. 6457 - 6457

Published: Sept. 4, 2020

The volume, composition, and movement of the cerebrospinal fluid (CSF) are important for brain physiology, pathology, diagnostics. Nevertheless, few studies have focused on main structure that produces CSF, choroid plexus (CP). Due to presence monocarboxylate transporters (MCTs) in CP, changes blood lactate levels reflected CSF. A receptor, hydroxycarboxylic acid receptor 1 (HCA

Language: Английский

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The brain as a source and a target of prolactin in mammals

Neural Regeneration Research, Journal Year: 2021, Volume and Issue: 17(8), P. 1695 - 1695

Published: Dec. 10, 2021

Prolactin is a polypeptide hormone associated with an extensive variety of biological functions. Among the roles prolactin in vertebrates, some were preserved throughout evolution. This case its function brain, where receptors, are expressed different structures central nervous system. In actions principally reproduction and parental behavior, involves modulation adult neurogenesis, neuroprotection, neuroplasticity, especially during pregnancy, thereby preparing brain to parenthood. mainly produced by specialized cells anterior pituitary gland. However, vertebrate evolution many other extrapituitary tissues do also produce prolactin, like immune system, endothelial cells, reproductive several regions brain. review summarizes relevance for function, sources as well local production secretion. A highlight on impact human neurological diseases provided.

Language: Английский

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