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Fluids and Barriers of the CNS
Published in: Fluids and Barriers of the CNS 1/2018

Open Access 01-12-2018 | Research

Cerebral influx of Na+ and Cl− as the osmotherapy-mediated rebound response in rats

Authors: Eva Kjer Oernbo, Kasper Lykke, Annette Buur Steffensen, Kathrin Töllner, Christina Kruuse, Martin Fredensborg Rath, Wolfgang Löscher, Nanna MacAulay

Published in: Fluids and Barriers of the CNS | Issue 1/2018

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Abstract

Background

Cerebral edema can cause life-threatening increase in intracranial pressure. Besides surgical craniectomy performed in severe cases, osmotherapy may be employed to lower the intracranial pressure by osmotic extraction of cerebral fluid upon intravenous infusion of mannitol or NaCl. A so-called rebound effect can, however, hinder continuous reduction in cerebral fluid by yet unresolved mechanisms.

Methods

We determined the brain water and electrolyte content in healthy rats treated with osmotherapy. Osmotherapy (elevated plasma osmolarity) was mediated by intraperitoneal injection of NaCl or mannitol with inclusion of pharmacological inhibitors of selected ion-transporters present at the capillary lumen or choroidal membranes. Brain barrier integrity was determined by fluorescence detection following intravenous delivery of Na+-fluorescein.

Results

NaCl was slightly more efficient than mannitol as an osmotic agent. The brain water loss was only ~ 60% of that predicted from ideal osmotic behavior, which could be accounted for by cerebral Na+ and Cl− accumulation. This electrolyte accumulation represented the majority of the rebound response, which was unaffected by the employed pharmacological agents. The brain barriers remained intact during the elevated plasma osmolarity.

Conclusions

A brain volume regulatory response occurs during osmotherapy, leading to the rebound response. This response involves brain accumulation of Na+ and Cl− and takes place by unresolved molecular mechanisms that do not include the common ion-transporting mechanisms located in the capillary endothelium at the blood–brain barrier and in the choroid plexus epithelium at the blood–CSF barrier. Future identification of these ion-transporting routes could provide a pharmacological target to prevent the rebound effect associated with the widely used osmotherapy.
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Metadata
Title
Cerebral influx of Na+ and Cl− as the osmotherapy-mediated rebound response in rats
Authors
Eva Kjer Oernbo
Kasper Lykke
Annette Buur Steffensen
Kathrin Töllner
Christina Kruuse
Martin Fredensborg Rath
Wolfgang Löscher
Nanna MacAulay
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Fluids and Barriers of the CNS / Issue 1/2018
Electronic ISSN: 2045-8118
DOI
https://doi.org/10.1186/s12987-018-0111-8

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