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Acetazolamide modulates intracranial pressure directly by its action on the cerebrospinal fluid secretion apparatus.
Barbuskaite, Dagne; Oernbo, Eva K; Wardman, Jonathan H; Toft-Bertelsen, Trine L; Conti, Eller; Andreassen, Søren N; Gerkau, Niklas J; Rose, Christine R; MacAulay, Nanna.
Afiliación
  • Barbuskaite D; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.
  • Oernbo EK; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.
  • Wardman JH; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.
  • Toft-Bertelsen TL; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.
  • Conti E; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.
  • Andreassen SN; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.
  • Gerkau NJ; Institute of Neurobiology, Heinrich Heine University, Universitätsstrasse 1, 40225, Düsseldorf, Germany.
  • Rose CR; Institute of Neurobiology, Heinrich Heine University, Universitätsstrasse 1, 40225, Düsseldorf, Germany.
  • MacAulay N; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark. macaulay@sund.ku.dk.
Fluids Barriers CNS ; 19(1): 53, 2022 Jun 29.
Article en En | MEDLINE | ID: mdl-35768824
BACKGROUND: Elevated intracranial pressure (ICP) is observed in many neurological pathologies, e.g. hydrocephalus and stroke. This condition is routinely relieved with neurosurgical approaches, since effective and targeted pharmacological tools are still lacking. The carbonic anhydrase inhibitor, acetazolamide (AZE), may be employed to treat elevated ICP. However, its effectiveness is questioned, its location of action unresolved, and its tolerability low. Here, we determined the efficacy and mode of action of AZE in the rat . METHODS: We employed in vivo approaches including ICP and cerebrospinal fluid secretion measurements in anaesthetized rats and telemetric monitoring of ICP and blood pressure in awake rats in combination with ex vivo choroidal radioisotope flux assays and transcriptomic analysis. RESULTS: AZE effectively reduced the ICP, irrespective of the mode of drug administration and level of anaesthesia. The effect appeared to occur via a direct action on the choroid plexus and an associated decrease in cerebrospinal fluid secretion, and not indirectly via the systemic action of AZE on renal and vascular processes. Upon a single administration, the reduced ICP endured for approximately 10 h post-AZE delivery with no long-term changes of brain water content or choroidal transporter expression. However, a persistent reduction of ICP was secured with repeated AZE administrations throughout the day. CONCLUSIONS: AZE lowers ICP directly via its ability to reduce the choroid plexus CSF secretion, irrespective of mode of drug administration.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Presión Intracraneal / Hipertensión Intracraneal Límite: Animals Idioma: En Revista: Fluids Barriers CNS Año: 2022 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Presión Intracraneal / Hipertensión Intracraneal Límite: Animals Idioma: En Revista: Fluids Barriers CNS Año: 2022 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido