Acetazolamide modulates intracranial pressure directly by its action on the cerebrospinal fluid secretion apparatus.

Acetazolamide / metabolism Animals Carbonic Anhydrase Inhibitors / pharmacology Cerebrospinal Fluid / metabolism Choroid Plexus / metabolism Intracranial Hypertension / drug therapy Intracranial Pressure / physiology Rats
CSF secretion Choroid plexus HCO3 − transporters Hydrocephalus ICP IIH

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:
29 Jun 2022
Historique:
received: 31 03 2022
accepted: 01 06 2022
entrez: 29 6 2022
pubmed: 30 6 2022
medline: 2 7 2022
Statut: epublish

Résumé

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 . 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. 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. AZE lowers ICP directly via its ability to reduce the choroid plexus CSF secretion, irrespective of mode of drug administration.

Sections du résumé

BACKGROUND 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 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 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 CONCLUSIONS
AZE lowers ICP directly via its ability to reduce the choroid plexus CSF secretion, irrespective of mode of drug administration.

Identifiants

DOI: 10.1186/s12987-022-00348-6 PMID: 35768824 PMC: PMC9245291
pubmed: 35768824
doi: 10.1186/s12987-022-00348-6
pii: 10.1186/s12987-022-00348-6
pmc: PMC9245291
doi:

Substances chimiques

Carbonic Anhydrase Inhibitors 0
Acetazolamide O3FX965V0I

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

53

Subventions

Organisme : Lundbeckfonden,Denmark
ID : R303-2018-3005
Organisme : Deutsche Forschungsgemeinschaft
ID : FOR2795
Organisme : Novo Nordisk Fonden
ID : NNF17OC0024718
Organisme : Lundbeckfonden
ID : R276-2018-403

Informations de copyright

© 2022. The Author(s).

Références

Curr Top Med Chem. 2007;7(9):825-33
pubmed: 17504127
J Pharmacol Exp Ther. 1970 Apr;172(2):197-202
pubmed: 5441150
N Engl J Med. 1954 May 6;250(18):759-64
pubmed: 13165895
J Appl Physiol (1985). 2015 Sep 1;119(5):576-81
pubmed: 26159754
Brain Res Bull. 1985 Sep;15(3):321-8
pubmed: 3931862
J Appl Physiol (1985). 1987 Nov;63(5):2134-41
pubmed: 3121580
Am J Pathol. 2001 Mar;158(3):905-19
pubmed: 11238039
J Neurosurg. 1978 Aug;49(2):256-63
pubmed: 671078
J Neurosci Methods. 2015 Feb 15;241:78-84
pubmed: 25554415
J Appl Physiol (1985). 1998 Feb;84(2):683-94
pubmed: 9475881
J Neurosurg. 1974 Sep;41(3):350-5
pubmed: 4413096
Fluids Barriers CNS. 2016 Feb 05;13:3
pubmed: 26846184
Exp Neurol. 2015 May;267:78-86
pubmed: 25747036
Proc Soc Exp Biol Med. 1954 Nov;87(2):373-6
pubmed: 13237248
J Neurophysiol. 1960 Sep;23:485-95
pubmed: 13743963
J Pharmacol Exp Ther. 1974 Apr;189(1):194-201
pubmed: 4207244
Nat Rev Neurosci. 2021 Jun;22(6):326-344
pubmed: 33846637
Life (Basel). 2021 Jul 20;11(7):
pubmed: 34357090
Neurosci Lett. 1993 Mar 19;151(2):162-5
pubmed: 8506074
PLoS One. 2012;7(9):e45976
pubmed: 23029347
Cochrane Database Syst Rev. 2001;(2):CD002270
pubmed: 11406041
Neurosci Lett. 2017 Apr 3;645:33-39
pubmed: 28219789
Proc Natl Acad Sci U S A. 1990 Jul;87(14):5278-82
pubmed: 2371270
Can J Physiol Pharmacol. 1982 Mar;60(3):405-9
pubmed: 7074425
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
J Physiol. 2011 Jun 15;589(Pt 12):3039-48
pubmed: 21521758
BMJ Open Respir Res. 2020 Apr;7(1):
pubmed: 32332024
Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1918-23
pubmed: 11172051
Anal Biochem. 2006 Mar 15;350(2):165-70
pubmed: 16480680
Acta Neuropathol Commun. 2020 Mar 19;8(1):35
pubmed: 32192527
Am J Physiol. 1994 Dec;267(6 Pt 1):C1616-22
pubmed: 7810603
J Biol Chem. 2011 Sep 16;286(37):32563-74
pubmed: 21705333
Brain Res. 1981 Sep 21;221(1):171-83
pubmed: 6791768
Biochem Biophys Res Commun. 2008 Sep 5;373(4):550-4
pubmed: 18588858
Br J Pharmacol. 2010 Aug;160(7):1577-9
pubmed: 20649561
J Clin Sleep Med. 2018 Mar 15;14(3):309-317
pubmed: 29510792
Arch Dis Child. 2001 Jan;84(1):68-71
pubmed: 11124792
J Pharmacol Exp Ther. 1990 Jul;254(1):23-7
pubmed: 2114478
Curr Opin Anaesthesiol. 2019 Oct;32(5):568-573
pubmed: 31211719
Ann Am Thorac Soc. 2017 Jul;14(7):1086-1093
pubmed: 28622013
BMC Dev Biol. 2006 May 23;6:22
pubmed: 16719910
Am J Physiol Cell Physiol. 2005 Dec;289(6):C1448-56
pubmed: 16093277
J Pharmacol Exp Ther. 1980 Dec;215(3):673-80
pubmed: 7441525
Arch Ophthalmol. 1979 Feb;97(2):280-3
pubmed: 550796
Physiol Rev. 2013 Oct;93(4):1847-92
pubmed: 24137023
J Neurosurg. 1966 Oct;25(4):430-6
pubmed: 5925714
J Histochem Cytochem. 1982 Apr;30(4):283-92
pubmed: 6801110
Am J Physiol Cell Physiol. 2004 Mar;286(3):C601-10
pubmed: 14592810
Nat Commun. 2018 Jun 4;9(1):2167
pubmed: 29867199
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
J Neurosci. 2015 Mar 25;35(12):4903-16
pubmed: 25810521
J Appl Physiol. 1972 May;32(5):612-7
pubmed: 5038848
Jpn J Physiol. 1986;36(3):523-32
pubmed: 3095576
Am J Physiol. 1977 Apr;232(4):F291-7
pubmed: 403777
Cochrane Database Syst Rev. 2015 Aug 07;(8):CD003434
pubmed: 26250102
Dement Neuropsychol. 2019 Apr-Jun;13(2):133-143
pubmed: 31285787
Am J Physiol. 1972 Sep;223(3):503-6
pubmed: 5055305
BMJ. 2019 Jul 24;366:l4225
pubmed: 31340932
J Neuroophthalmol. 2017 Jun;37(2):182-186
pubmed: 28376023
Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):311-6
pubmed: 18165320
BMC Bioinformatics. 2019 Dec 20;20(Suppl 24):679
pubmed: 31861985
Transl Stroke Res. 2019 Aug;10(4):428-439
pubmed: 30225552
Am J Physiol. 1963 Sep;205:617-24
pubmed: 14065919
J Physiol. 1965 Dec;181(3):516-24
pubmed: 5880375
Br J Anaesth. 2003 Jul;91(1):40-9
pubmed: 12821564
Am J Physiol. 1990 Jan;258(1 Pt 2):R94-8
pubmed: 2137302
Glia. 2021 Jan;69(1):28-41
pubmed: 32506554
Lancet. 1957 Nov 9;273(7002):926-7
pubmed: 13482249
Am J Physiol. 1963 Oct;205:693-6
pubmed: 14060806
Crit Care Clin. 2006 Oct;22(4):713-32; abstract ix
pubmed: 17239751
Cephalalgia. 2019 Feb;39(2):209-218
pubmed: 29898611
J Pharmacol Exp Ther. 1987 Oct;243(1):35-9
pubmed: 3668863
Transl Stroke Res. 2012 Mar;3(1):130-7
pubmed: 22400066
J Physiol. 1970 Jul;209(1):131-53
pubmed: 5499038
Neurology. 2014 Apr 15;82(15):1347-51
pubmed: 24634454

Auteurs

Dagne Barbuskaite (D)

Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.

Eva K Oernbo (EK)

Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.

Jonathan H Wardman (JH)

Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.

Trine L Toft-Bertelsen (TL)

Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.

Eller Conti (E)

Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.

Søren N Andreassen (SN)

Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.

Niklas J Gerkau (NJ)

Institute of Neurobiology, Heinrich Heine University, Universitätsstrasse 1, 40225, Düsseldorf, Germany.

Christine R Rose (CR)

Institute of Neurobiology, Heinrich Heine University, Universitätsstrasse 1, 40225, Düsseldorf, Germany.

Nanna MacAulay (N)

Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark. macaulay@sund.ku.dk.
ORCID: 0000-0002-7800-6600

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Classifications MeSH

Recherchemedicale.com › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Thiazoles › Thiadiazoles › Acétazolamide › Acetazolamide modulates intracranial pressure...
Recherchemedicale.com › Eucaryotes › Animaux › Acetazolamide modulates intracranial pressure...
Recherchemedicale.com › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Inhibiteurs de l'anhydrase carbonique › Acetazolamide modulates intracranial pressure...
Recherchemedicale.com › Liquides et sécrétions biologiques › Liquides biologiques › Liquide extracellulaire › Liquide cérébrospinal › Acetazolamide modulates intracranial pressure...
Recherchemedicale.com › Système nerveux › Système nerveux central › Encéphale › Ventricules cérébraux › Plexus choroïde › Acetazolamide modulates intracranial pressure...
Recherchemedicale.com › Maladies du système nerveux › Maladies du système nerveux central › Encéphalopathies › Hypertension intracrânienne › Acetazolamide modulates intracranial pressure...
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