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

Annette Buur Steffensen, Beatriche Louise Edelbo, Dagne Barbuskaite, Søren Norge Andreassen, Markus Harboe Olsen, Kirsten Møller, Nanna MacAulay*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

13 Citationer (Scopus)
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Abstract

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
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
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+,K+,2Cl- cotransporter (NKCC1), which is implicated in CSF secretion by this tissue.

Conclusion
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.
OriginalsprogEngelsk
Artikelnummer49
TidsskriftFluids and Barriers of the CNS
Vol/bind20
Udgave nummer1
Antal sider14
ISSN2045-8118
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
Open access funding provided by Royal Library, Copenhagen University Library. The study was funded by the Lundbeck Foundation (ascending investigator grant, R313-2019-735 to NM and R276-2018-403 to NM) and the Novo Nordisk Foundation (Tandem grant, NNF17OC0024718 to NM).

Publisher Copyright:
© 2023, The Author(s).

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