Nocturnal increase in cerebrospinal fluid secretion as a circadian regulator of intracranial pressure.

Cerebrospinal fluid Choroid plexus Circadian rhythm Intracranial pressure Na+,K+,2Cl− cotransporter Na+/K+-ATPase Sleep

Journal

Fluids and barriers of the CNS
ISSN: 2045-8118
Titre abrégé: Fluids Barriers CNS
Pays: England
ID NLM: 101553157

Informations de publication

Date de publication:
23 Jun 2023
Historique:
received: 28 02 2023
accepted: 06 06 2023
medline: 26 6 2023
pubmed: 24 6 2023
entrez: 23 6 2023
Statut: epublish

Résumé

It is crucial to maintain the intracranial pressure (ICP) within the physiological range to ensure proper brain function. The ICP may fluctuate during the light-dark phase cycle, complicating diagnosis and treatment choice in patients with pressure-related disorders. Such ICP fluctuations may originate in circadian or sleep-wake cycle-mediated modulation of cerebrospinal fluid (CSF) flow dynamics, which in addition could support diurnal regulation of brain waste clearance. ICP was monitored continuously in patients who underwent placement of an external ventricular drain (EVD) and by telemetric monitoring in experimental rats. CSF was collected via the EVD in patients and the rodent CSF secretion rate determined by in vivo experimentation. Rodent choroid plexus transporter transcripts were quantified with RNAseq and transport activity with ex vivo isotope transport assays. We demonstrated that ICP increases by 30% in the dark phase in both species, independently of vascular parameters. This increase aligns with elevated CSF collection in patients (12%) and CSF production rate in rats (20%), the latter obtained with the ventriculo-cisternal perfusion assay. The dark-phase increase in CSF secretion in rats was, in part, assigned to increased transport activity of the choroid plexus Na CSF secretion, and thus ICP, increases in the dark phase in humans and rats, irrespective of their diurnal/nocturnal activity preference, in part due to altered choroid plexus transport activity in the rat. Our findings suggest that CSF dynamics are modulated by the circadian rhythm, rather than merely sleep itself.

Sections du résumé

BACKGROUND BACKGROUND
It is crucial to maintain the intracranial pressure (ICP) within the physiological range to ensure proper brain function. The ICP may fluctuate during the light-dark phase cycle, complicating diagnosis and treatment choice in patients with pressure-related disorders. Such ICP fluctuations may originate in circadian or sleep-wake cycle-mediated modulation of cerebrospinal fluid (CSF) flow dynamics, which in addition could support diurnal regulation of brain waste clearance.
METHODS METHODS
ICP was monitored continuously in patients who underwent placement of an external ventricular drain (EVD) and by telemetric monitoring in experimental rats. CSF was collected via the EVD in patients and the rodent CSF secretion rate determined by in vivo experimentation. Rodent choroid plexus transporter transcripts were quantified with RNAseq and transport activity with ex vivo isotope transport assays.
RESULTS RESULTS
We demonstrated that ICP increases by 30% in the dark phase in both species, independently of vascular parameters. This increase aligns with elevated CSF collection in patients (12%) and CSF production rate in rats (20%), the latter obtained with the ventriculo-cisternal perfusion assay. The dark-phase increase in CSF secretion in rats was, in part, assigned to increased transport activity of the choroid plexus Na
CONCLUSION CONCLUSIONS
CSF secretion, and thus ICP, increases in the dark phase in humans and rats, irrespective of their diurnal/nocturnal activity preference, in part due to altered choroid plexus transport activity in the rat. Our findings suggest that CSF dynamics are modulated by the circadian rhythm, rather than merely sleep itself.

Identifiants

pubmed: 37353833
doi: 10.1186/s12987-023-00451-2
pii: 10.1186/s12987-023-00451-2
pmc: PMC10290349
doi:

Substances chimiques

Membrane Transport Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

49

Subventions

Organisme : Lundbeckfonden
ID : R313-2019-735 and R276-2018-403
Organisme : Novo Nordisk Fonden
ID : NNF17OC0024718

Informations de copyright

© 2023. The Author(s).

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Auteurs

Annette Buur Steffensen (AB)

Faculty of Health and Medical Sciences, Department of Neuroscience, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen N, Denmark.

Beatriche Louise Edelbo (BL)

Faculty of Health and Medical Sciences, Department of Neuroscience, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen N, Denmark.

Dagne Barbuskaite (D)

Faculty of Health and Medical Sciences, Department of Neuroscience, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen N, Denmark.

Søren Norge Andreassen (SN)

Faculty of Health and Medical Sciences, Department of Neuroscience, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen N, Denmark.

Markus Harboe Olsen (MH)

Department of Neuroanaesthesiology, The Neuroscience Center, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

Kirsten Møller (K)

Department of Neuroanaesthesiology, The Neuroscience Center, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

Nanna MacAulay (N)

Faculty of Health and Medical Sciences, Department of Neuroscience, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen N, Denmark. macaulay@sund.ku.dk.

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