CSF hyperdynamics in rats mimicking the obesity and androgen excess characteristic of patients with idiopathic intracranial hypertension
Abstract Background Idiopathic intracranial hypertension (IIH) is a syndrome exhibiting elevated intracranial pressure (ICP), visual disturbances, and severe headache. IIH primarily affects young obese women, though it can occur in individuals of any age, BMI, and sex. IIH is characterized by system...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Fluids and Barriers of the CNS |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12987-024-00511-1 |
| _version_ | 1797276328638021632 |
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| author | Jonathan H. Wardman Søren Norge Andreassen Trine L. Toft-Bertelsen Mette Nyholm Jensen Jens E. Wilhjelm Bjarne Styrishave Steffen Hamann Steffen Heegaard Alexandra J. Sinclair Nanna MacAulay |
| author_facet | Jonathan H. Wardman Søren Norge Andreassen Trine L. Toft-Bertelsen Mette Nyholm Jensen Jens E. Wilhjelm Bjarne Styrishave Steffen Hamann Steffen Heegaard Alexandra J. Sinclair Nanna MacAulay |
| author_sort | Jonathan H. Wardman |
| collection | DOAJ |
| description | Abstract Background Idiopathic intracranial hypertension (IIH) is a syndrome exhibiting elevated intracranial pressure (ICP), visual disturbances, and severe headache. IIH primarily affects young obese women, though it can occur in individuals of any age, BMI, and sex. IIH is characterized by systemic metabolic dysregulation with a profile of increased androgen hormones. However, the contribution of obesity/hormonal perturbations to cerebrospinal fluid (CSF) dynamics remains unresolved. Methods We employed obese female Zucker rats and adjuvant testosterone to reveal IIH causal drivers. ICP and CSF dynamics were determined with in vivo experimentation and magnetic resonance imaging, testosterone levels assessed with mass spectrometry, and choroid plexus function revealed with transcriptomics. Results Obese rats had undisturbed CSF testosterone levels and no changes in ICP or CSF dynamics. Adjuvant testosterone treatment of obese rats elevated the CSF secretion rate, although with no effect on the ICP, due to elevated CSF drainage capacity of these rats. Conclusions Obesity in itself therefore does not suffice to recapitulate the IIH symptoms in rats, but modulation of CSF dynamics appears with adjuvant testosterone treatment, which mimics the androgen excess observed in female IIH patients. Obesity-induced androgen dysregulation may thus contribute to the disease mechanism of IIH and could potentially serve as a future therapeutic target. |
| first_indexed | 2024-03-07T15:26:42Z |
| format | Article |
| id | doaj.art-5f7a8343575f4f48aa2f4921bab051fa |
| institution | Directory Open Access Journal |
| issn | 2045-8118 |
| language | English |
| last_indexed | 2024-03-07T15:26:42Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Fluids and Barriers of the CNS |
| spelling | doaj.art-5f7a8343575f4f48aa2f4921bab051fa2024-03-05T16:38:56ZengBMCFluids and Barriers of the CNS2045-81182024-01-0121112010.1186/s12987-024-00511-1CSF hyperdynamics in rats mimicking the obesity and androgen excess characteristic of patients with idiopathic intracranial hypertensionJonathan H. Wardman0Søren Norge Andreassen1Trine L. Toft-Bertelsen2Mette Nyholm Jensen3Jens E. Wilhjelm4Bjarne Styrishave5Steffen Hamann6Steffen Heegaard7Alexandra J. Sinclair8Nanna MacAulay9Department of Neuroscience, University of CopenhagenDepartment of Neuroscience, University of CopenhagenDepartment of Neuroscience, University of CopenhagenDepartment of Neuroscience, University of CopenhagenDepartment of Neurophysiology, RigshospitaletDepartment of Pharmacy, University of CopenhagenDepartment of Ophthalmology, RigshospitaletDepartment of Ophthalmology, RigshospitaletInstitute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of BirminghamDepartment of Neuroscience, University of CopenhagenAbstract Background Idiopathic intracranial hypertension (IIH) is a syndrome exhibiting elevated intracranial pressure (ICP), visual disturbances, and severe headache. IIH primarily affects young obese women, though it can occur in individuals of any age, BMI, and sex. IIH is characterized by systemic metabolic dysregulation with a profile of increased androgen hormones. However, the contribution of obesity/hormonal perturbations to cerebrospinal fluid (CSF) dynamics remains unresolved. Methods We employed obese female Zucker rats and adjuvant testosterone to reveal IIH causal drivers. ICP and CSF dynamics were determined with in vivo experimentation and magnetic resonance imaging, testosterone levels assessed with mass spectrometry, and choroid plexus function revealed with transcriptomics. Results Obese rats had undisturbed CSF testosterone levels and no changes in ICP or CSF dynamics. Adjuvant testosterone treatment of obese rats elevated the CSF secretion rate, although with no effect on the ICP, due to elevated CSF drainage capacity of these rats. Conclusions Obesity in itself therefore does not suffice to recapitulate the IIH symptoms in rats, but modulation of CSF dynamics appears with adjuvant testosterone treatment, which mimics the androgen excess observed in female IIH patients. Obesity-induced androgen dysregulation may thus contribute to the disease mechanism of IIH and could potentially serve as a future therapeutic target.https://doi.org/10.1186/s12987-024-00511-1Choroid plexusIIHCerebrospinal fluidTestosteroneSex hormonesIntracranial pressure |
| spellingShingle | Jonathan H. Wardman Søren Norge Andreassen Trine L. Toft-Bertelsen Mette Nyholm Jensen Jens E. Wilhjelm Bjarne Styrishave Steffen Hamann Steffen Heegaard Alexandra J. Sinclair Nanna MacAulay CSF hyperdynamics in rats mimicking the obesity and androgen excess characteristic of patients with idiopathic intracranial hypertension Fluids and Barriers of the CNS Choroid plexus IIH Cerebrospinal fluid Testosterone Sex hormones Intracranial pressure |
| title | CSF hyperdynamics in rats mimicking the obesity and androgen excess characteristic of patients with idiopathic intracranial hypertension |
| title_full | CSF hyperdynamics in rats mimicking the obesity and androgen excess characteristic of patients with idiopathic intracranial hypertension |
| title_fullStr | CSF hyperdynamics in rats mimicking the obesity and androgen excess characteristic of patients with idiopathic intracranial hypertension |
| title_full_unstemmed | CSF hyperdynamics in rats mimicking the obesity and androgen excess characteristic of patients with idiopathic intracranial hypertension |
| title_short | CSF hyperdynamics in rats mimicking the obesity and androgen excess characteristic of patients with idiopathic intracranial hypertension |
| title_sort | csf hyperdynamics in rats mimicking the obesity and androgen excess characteristic of patients with idiopathic intracranial hypertension |
| topic | Choroid plexus IIH Cerebrospinal fluid Testosterone Sex hormones Intracranial pressure |
| url | https://doi.org/10.1186/s12987-024-00511-1 |
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