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

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-...

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Autores principales: Oernbo, Eva Kjer, Lykke, Kasper, Steffensen, Annette Buur, Töllner, Kathrin, Kruuse, Christina, Rath, Martin Fredensborg, Löscher, Wolfgang, MacAulay, Nanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154956/
https://www.ncbi.nlm.nih.gov/pubmed/30249273
http://dx.doi.org/10.1186/s12987-018-0111-8
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author Oernbo, Eva Kjer
Lykke, Kasper
Steffensen, Annette Buur
Töllner, Kathrin
Kruuse, Christina
Rath, Martin Fredensborg
Löscher, Wolfgang
MacAulay, Nanna
author_facet Oernbo, Eva Kjer
Lykke, Kasper
Steffensen, Annette Buur
Töllner, Kathrin
Kruuse, Christina
Rath, Martin Fredensborg
Löscher, Wolfgang
MacAulay, Nanna
author_sort Oernbo, Eva Kjer
collection PubMed
description 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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spelling pubmed-61549562018-09-26 Cerebral influx of Na(+) and Cl(−) as the osmotherapy-mediated rebound response in rats Oernbo, Eva Kjer Lykke, Kasper Steffensen, Annette Buur Töllner, Kathrin Kruuse, Christina Rath, Martin Fredensborg Löscher, Wolfgang MacAulay, Nanna Fluids Barriers CNS Research 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. BioMed Central 2018-09-25 /pmc/articles/PMC6154956/ /pubmed/30249273 http://dx.doi.org/10.1186/s12987-018-0111-8 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Oernbo, Eva Kjer
Lykke, Kasper
Steffensen, Annette Buur
Töllner, Kathrin
Kruuse, Christina
Rath, Martin Fredensborg
Löscher, Wolfgang
MacAulay, Nanna
Cerebral influx of Na(+) and Cl(−) as the osmotherapy-mediated rebound response in rats
title Cerebral influx of Na(+) and Cl(−) as the osmotherapy-mediated rebound response in rats
title_full Cerebral influx of Na(+) and Cl(−) as the osmotherapy-mediated rebound response in rats
title_fullStr Cerebral influx of Na(+) and Cl(−) as the osmotherapy-mediated rebound response in rats
title_full_unstemmed Cerebral influx of Na(+) and Cl(−) as the osmotherapy-mediated rebound response in rats
title_short Cerebral influx of Na(+) and Cl(−) as the osmotherapy-mediated rebound response in rats
title_sort cerebral influx of na(+) and cl(−) as the osmotherapy-mediated rebound response in rats
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154956/
https://www.ncbi.nlm.nih.gov/pubmed/30249273
http://dx.doi.org/10.1186/s12987-018-0111-8
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