Potential role of the Virchow Robin space in the pathogenesis of bacterial meningitis

Chan, Patrick; Meerdink, Denis J.; Uchizono, James A.

doi:10.1016/j.mehy.2017.09.014

Cited by 4 publications

(3 citation statements)

References 57 publications

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“…The subarachnoid space within the leptomeninges is bathed in ChP-derived CSF and plays a crucial role in protecting the CNS. The anatomical relationship of the vascular cells, meninges and ChP through the subarachnoid, Virchow-Robin/perivascular space and the CSF-containing ventricles allows for the exchange of fluid components be it therapeutics or less desired inflammatory constituents 59 . However, the meninges and ChP can also contribute to numerous neurological disorders, due to their intimate interactions and exposure to the peripheral environment respectively through the meningeal lymphatics and the fenestrated blood vessels 30,[60][61][62] .…”

Section: Resultsmentioning

confidence: 99%

Cardiac glycosides target barrier inflammation of the vasculature, meninges and choroid plexus

et al. 2021

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Neuroinflammation is a key component of virtually all neurodegenerative diseases, preceding neuronal loss and associating directly with cognitive impairment. Neuroinflammatory signals can originate and be amplified at barrier tissues such as brain vasculature, surrounding meninges and the choroid plexus. We designed a high content screening system to target inflammation in human brain-derived cells of the blood–brain barrier (pericytes and endothelial cells) to identify inflammatory modifiers. Screening an FDA-approved drug library we identify digoxin and lanatoside C, members of the cardiac glycoside family, as inflammatory-modulating drugs that work in blood–brain barrier cells. An ex vivo assay of leptomeningeal and choroid plexus explants confirm that these drugs maintain their function in 3D cultures of brain border tissues. These results suggest that cardiac glycosides may be useful in targeting inflammation at border regions of the brain and offer new options for drug discovery approaches for neuroinflammatory driven degeneration.

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Section: Resultsmentioning

confidence: 99%

Cardiac glycosides target barrier inflammation of the vasculature, meninges and choroid plexus

et al. 2021

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“…The subarachnoid space within the leptomeninges is bathed in CP-derived CSF and plays a crucial role in protecting the CNS. The anatomical relationship of the vascular cells, meninges, and CP through the subarachnoid, Virchow-robin/perivascular space, and the CSF-containing ventricles allows for the exchange of fluid components be it therapeutics or less desired inflammatory constituents ( 53 ). However, the meninges and CP can also contribute to numerous neurological disorders, due to their intimate interactions and exposure to the peripheral environment respectively through the meningeal lymphatics and the fenestrated blood vessels ( 29, 54-56 ).…”

Section: Resultsmentioning

confidence: 99%

Recycling old drugs: cardiac glycosides as therapeutics to target barrier inflammation of the vasculature, meninges and choroid plexus

Jansson

Dieriks

Rustenhoven

et al. 2020

Preprint

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Neuroinflammation is a key component of virtually all neurodegenerative diseases; preceding neuronal loss and associating directly with cognitive impairment. Neuroinflammatory signals can originate and be amplified at barrier tissues such as brain vasculature, surrounding meninges and the choroid plexus. We designed a high-throughput screening system to target inflammation in cells of the blood-brain barrier (primary human pericytes and endothelia) and microglia enabling us to target human disease-specific inflammatory modifiers. Screening an FDA-approved drug library we identified digoxin and lanatoside C, members of the cardiac glycoside family as inflammatory modulating drugs that work in blood-brain barrier cells. A novel ex vivo assay of leptomeningeal and choroid plexus explants further confirmed that these drugs maintain their function in 3D cultures of brain border tissues. While current therapeutic strategies for the treatment of neurodegenerative diseases are missing the mark in terms of targets, efficacy and translatability, our innovative approach using in vitro and ex vivo human barrier cells and tissues to target neuroinflammatory pathways is a step forward in drug development and testing, and brings us closer to translatable treatments for human neurodegenerative disease.One Sentence SummaryWe have identified cardiac glycosides as powerful regulators of neuroinflammatory pathways in brain-barrier tissues such as vasculature, meninges and choroid plexus.

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“…Robin и другие исследователи описывали именно периваскулярное пространство ЦНС, то есть воронкообразные углубления в зоне вхож дения сосудов в ткань ГМ. В большинс тве современных публикаций, посвященных нейровизуализации, пространство Вирхова-Робина и ПВП являются синонимами [42,50]. В ряде работ, отражающих морфологические аспекты строения ЦНС под пространством Вирхова-Робина понимают интраадвентициальную полость, отграниченную глиальной оболочкой, покрывающей ткань мозга и адвентицию сосуда, с одной стороны, и элементами пиальной оболочки -с другой [51].…”

Section: циркуляция цереброспинальной жидкостиunclassified

Cerebrospinal fluid flow. Part 1. Classical theory and its evolution

Слынько

Nekhlopochyn

2018

Ukr Neurosurg J

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Цереброспинальная жидкость играет огромную физиологическую роль в нормальном функционировании центральной нервной системы человека. Ее изменения служат своего рода индикатором большого количества патологических процессов. Однако анализ литературы выявил небольшое количество работ, посвященных детальному описанию механизмов ликвородинамики. Несмотря на усовершенствование экспериментальных методик, использование электронной микроскопии, радиоизотопных и иммунологических методов, многие аспекты циркуляции цереброспинальной жидкости остаются не изученными. В обзоре сделана попытка упорядочить имеющиеся данные и осветить эволюцию представлений о ликвородинамике в историческом аспекте, опираясь на известные публикации.

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Potential role of the Virchow Robin space in the pathogenesis of bacterial meningitis

Cited by 4 publications

References 57 publications

Cardiac glycosides target barrier inflammation of the vasculature, meninges and choroid plexus

Cardiac glycosides target barrier inflammation of the vasculature, meninges and choroid plexus

Recycling old drugs: cardiac glycosides as therapeutics to target barrier inflammation of the vasculature, meninges and choroid plexus

Cerebrospinal fluid flow. Part 1. Classical theory and its evolution

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