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Modelling idiopathic intracranial hypertension in rats: contributions of high fat diet and testosterone to intracranial pressure and cerebrospinal fluid production.
Wardman, Jonathan H; Jensen, Mette N; Andreassen, Søren N; Styrishave, Bjarne; Wilhjelm, Jens E; Sinclair, Alexandra J; MacAulay, Nanna.
Afiliación
  • Wardman JH; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen N, Denmark.
  • Jensen MN; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen N, Denmark.
  • Andreassen SN; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen N, Denmark.
  • Styrishave B; Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
  • Wilhjelm JE; Department of Health Technology, The Technical University of Denmark, Kgs. Lyngby, Denmark.
  • Sinclair AJ; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
  • MacAulay N; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen N, Denmark. macaulay@sund.ku.dk.
Fluids Barriers CNS ; 20(1): 44, 2023 Jun 16.
Article en En | MEDLINE | ID: mdl-37328884
BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition characterized by increased intracranial pressure (ICP), impaired vision, and headache. Most cases of IIH occur in obese women of childbearing age, though age, BMI, and female sex do not encompass all aspects of IIH pathophysiology. Systemic metabolic dysregulation has been identified in IIH with a profile of androgen excess. However, the mechanistic coupling between obesity/hormonal perturbations and cerebrospinal fluid dynamics remains unresolved. METHODS: Female Wistar rats were either fed a high fat diet (HFD) for 21 weeks or exposed to adjuvant testosterone treatment for 28 days to recapitulate IIH causal drivers. Cerebrospinal fluid (CSF) and blood testosterone levels were determined with mass spectrometry, ICP and CSF dynamics with in vivo experimentation, and the choroid plexus function revealed with transcriptomics and ex vivo isotope-based flux assays. RESULTS: HFD-fed rats presented with increased ICP (65%), which was accompanied by increased CSF outflow resistance (50%) without altered CSF secretion rate or choroid plexus gene expression. Chronic adjuvant testosterone treatment of lean rats caused elevated ICP (55%) and CSF secretion rate (85%), in association with increased activity of the choroid plexus Na+,K+,2Cl- cotransporter, NKCC1. CONCLUSIONS: HFD-induced ICP elevation in experimental rats occurred with decreased CSF drainage capacity. Adjuvant testosterone, mimicking the androgen excess observed in female IIH patients, elevated the CSF secretion rate and thus ICP. Obesity-induced androgen dysregulation may thus contribute to the disease mechanism of IIH.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Seudotumor Cerebral / Hipertensión Intracraneal Límite: Animals Idioma: En Revista: Fluids Barriers CNS Año: 2023 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Seudotumor Cerebral / Hipertensión Intracraneal Límite: Animals Idioma: En Revista: Fluids Barriers CNS Año: 2023 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido