Disentangling the impact of cerebrospinal fluid formation and neuronal activity on solute clearance from the brain.
Brain state
CSF production
Ca2+ recordings
DCE MRI
DWI
Glymphatic system
Kinetic modeling
Solute clearance
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:
14 Jun 2023
14 Jun 2023
Historique:
received:
22
12
2022
accepted:
18
05
2023
medline:
16
6
2023
pubmed:
15
6
2023
entrez:
14
6
2023
Statut:
epublish
Résumé
Despite recent attention, pathways and mechanisms of fluid transposition in the brain are still a matter of intense discussion and driving forces underlying waste clearance in the brain remain elusive. Consensus exists that net solute transport is a prerequisite for efficient clearance. The individual impact of neuronal activity and cerebrospinal fluid (CSF) formation, which both vary with brain state and anesthesia, remain unclear. To separate conditions with high and low neuronal activity and high and low CSF formation, different anesthetic regimens in naive rat were established, using Isoflurane (ISO), Medetomidine (MED), acetazolamide or combinations thereof. With dynamic contrast-enhanced MRI, after application of low molecular weight contrast agent (CA) Gadobutrol to cisterna magna, tracer distribution was monitored as surrogate for solute clearance. Simultaneous fiber-based Ca Anatomical imaging, DWI and Ca Efficiency of solute clearance in brain changes with alterations in both state of neuronal activity and CSF formation. Our clearance pathway and mechanism agnostic kinetic model informs about net solute transport, solely based on the measured time signal curves. This rather simplifying approach largely accords with preclinical and clinical findings.
Sections du résumé
BACKGROUND
BACKGROUND
Despite recent attention, pathways and mechanisms of fluid transposition in the brain are still a matter of intense discussion and driving forces underlying waste clearance in the brain remain elusive. Consensus exists that net solute transport is a prerequisite for efficient clearance. The individual impact of neuronal activity and cerebrospinal fluid (CSF) formation, which both vary with brain state and anesthesia, remain unclear.
METHODS
METHODS
To separate conditions with high and low neuronal activity and high and low CSF formation, different anesthetic regimens in naive rat were established, using Isoflurane (ISO), Medetomidine (MED), acetazolamide or combinations thereof. With dynamic contrast-enhanced MRI, after application of low molecular weight contrast agent (CA) Gadobutrol to cisterna magna, tracer distribution was monitored as surrogate for solute clearance. Simultaneous fiber-based Ca
RESULTS
RESULTS
Anatomical imaging, DWI and Ca
CONCLUSIONS
CONCLUSIONS
Efficiency of solute clearance in brain changes with alterations in both state of neuronal activity and CSF formation. Our clearance pathway and mechanism agnostic kinetic model informs about net solute transport, solely based on the measured time signal curves. This rather simplifying approach largely accords with preclinical and clinical findings.
Identifiants
pubmed: 37316849
doi: 10.1186/s12987-023-00443-2
pii: 10.1186/s12987-023-00443-2
pmc: PMC10265831
doi:
Substances chimiques
Acetazolamide
O3FX965V0I
Contrast Media
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
43Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : 194468054-SFB1009-Z02
Informations de copyright
© 2023. The Author(s).
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