Glucocorticoids modify intracranial pressure in freely moving rats
Abstract Background Glucocorticoids (GCs) are widely prescribed for a variety of inflammatory diseases, but they are also used to treat raised intracranial pressure (ICP) caused by trauma or oedema. However, it is unclear if GCs independently modulate ICP and if GCs are involved in normal ICP regula...
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Fluids and Barriers of the CNS |
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| Online Access: | https://doi.org/10.1186/s12987-023-00439-y |
| _version_ | 1797817816416518144 |
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| author | Connar Stanley James Westgate Ida Marchen Egerod Israelsen Christina Kamp-Jensen Rigmor Højland Jensen Sajedeh Eftekhari |
| author_facet | Connar Stanley James Westgate Ida Marchen Egerod Israelsen Christina Kamp-Jensen Rigmor Højland Jensen Sajedeh Eftekhari |
| author_sort | Connar Stanley James Westgate |
| collection | DOAJ |
| description | Abstract Background Glucocorticoids (GCs) are widely prescribed for a variety of inflammatory diseases, but they are also used to treat raised intracranial pressure (ICP) caused by trauma or oedema. However, it is unclear if GCs independently modulate ICP and if GCs are involved in normal ICP regulation. In this study, we aimed to assess the ICP modulatory effects of GCs and their molecular consequences on choroid plexus (CP). Methods Adult female rats were implanted with telemetric ICP probes for physiological, continuous ICP recordings in a freely moving setup. Rats received prednisolone or vehicle via oral gavage in a randomized acute (24 h) ICP study. In a subsequent study rats received corticosterone or vehicle in drinking water for a 4-week chronic ICP study. CP were removed, and the expression of genes associated with cerebrospinal fluid secretion were assessed. Results A single prednisolone dose reduced ICP by up to 48% (P < 0.0001), where ICP was reduced within 7 h and was maintained for at least 14 h. Prednisolone increases ICP spiking (P = 0.0075) while not altering ICP waveforms. Chronic corticosterone reduces ICP by up to 44%, where ICP was lower for the entirety of the 4-week ICP recording period (P = 0.0064). ICP daily periodicity was not altered by corticosterone. Corticosterone ICP reduction was not accompanied by ICP spike differences or alteration in ICP spike periodicity. Chronic corticosterone treatment had modest effects on CP gene expression, lowering the expression of Car2 at CP (P = 0.047). Conclusions GCs reduce ICP in both the acute and chronic setting to a similar degree. Moreover, GCs did not modify the diurnal rhythm of ICP, suggesting the diurnal variation of ICP periodicity is not under explicit control of GCs. ICP disturbances should be considered a consequence of GC therapy. Based on these experiments, GCs may have broader ICP therapeutic uses, but side effects must be taken into consideration. |
| first_indexed | 2024-03-13T08:59:00Z |
| format | Article |
| id | doaj.art-05c753337e96422ba5a360a7d1d7f2a9 |
| institution | Directory Open Access Journal |
| issn | 2045-8118 |
| language | English |
| last_indexed | 2024-03-13T08:59:00Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Fluids and Barriers of the CNS |
| spelling | doaj.art-05c753337e96422ba5a360a7d1d7f2a92023-05-28T11:25:24ZengBMCFluids and Barriers of the CNS2045-81182023-05-0120111110.1186/s12987-023-00439-yGlucocorticoids modify intracranial pressure in freely moving ratsConnar Stanley James Westgate0Ida Marchen Egerod Israelsen1Christina Kamp-Jensen2Rigmor Højland Jensen3Sajedeh Eftekhari4Danish Headache Center, Dept of Neurology, Rigshospitalet-Glostrup, Glostrup Research Institute, University of CopenhagenDanish Headache Center, Dept of Neurology, Rigshospitalet-Glostrup, Glostrup Research Institute, University of CopenhagenDanish Headache Center, Dept of Neurology, Rigshospitalet-Glostrup, Glostrup Research Institute, University of CopenhagenDanish Headache Center, Dept of Neurology, Rigshospitalet-Glostrup, Glostrup Research Institute, University of CopenhagenDanish Headache Center, Dept of Neurology, Rigshospitalet-Glostrup, Glostrup Research Institute, University of CopenhagenAbstract Background Glucocorticoids (GCs) are widely prescribed for a variety of inflammatory diseases, but they are also used to treat raised intracranial pressure (ICP) caused by trauma or oedema. However, it is unclear if GCs independently modulate ICP and if GCs are involved in normal ICP regulation. In this study, we aimed to assess the ICP modulatory effects of GCs and their molecular consequences on choroid plexus (CP). Methods Adult female rats were implanted with telemetric ICP probes for physiological, continuous ICP recordings in a freely moving setup. Rats received prednisolone or vehicle via oral gavage in a randomized acute (24 h) ICP study. In a subsequent study rats received corticosterone or vehicle in drinking water for a 4-week chronic ICP study. CP were removed, and the expression of genes associated with cerebrospinal fluid secretion were assessed. Results A single prednisolone dose reduced ICP by up to 48% (P < 0.0001), where ICP was reduced within 7 h and was maintained for at least 14 h. Prednisolone increases ICP spiking (P = 0.0075) while not altering ICP waveforms. Chronic corticosterone reduces ICP by up to 44%, where ICP was lower for the entirety of the 4-week ICP recording period (P = 0.0064). ICP daily periodicity was not altered by corticosterone. Corticosterone ICP reduction was not accompanied by ICP spike differences or alteration in ICP spike periodicity. Chronic corticosterone treatment had modest effects on CP gene expression, lowering the expression of Car2 at CP (P = 0.047). Conclusions GCs reduce ICP in both the acute and chronic setting to a similar degree. Moreover, GCs did not modify the diurnal rhythm of ICP, suggesting the diurnal variation of ICP periodicity is not under explicit control of GCs. ICP disturbances should be considered a consequence of GC therapy. Based on these experiments, GCs may have broader ICP therapeutic uses, but side effects must be taken into consideration.https://doi.org/10.1186/s12987-023-00439-yIntracranial pressureGlucocorticoidPrednisoloneCorticosteroneChoroid plexus |
| spellingShingle | Connar Stanley James Westgate Ida Marchen Egerod Israelsen Christina Kamp-Jensen Rigmor Højland Jensen Sajedeh Eftekhari Glucocorticoids modify intracranial pressure in freely moving rats Fluids and Barriers of the CNS Intracranial pressure Glucocorticoid Prednisolone Corticosterone Choroid plexus |
| title | Glucocorticoids modify intracranial pressure in freely moving rats |
| title_full | Glucocorticoids modify intracranial pressure in freely moving rats |
| title_fullStr | Glucocorticoids modify intracranial pressure in freely moving rats |
| title_full_unstemmed | Glucocorticoids modify intracranial pressure in freely moving rats |
| title_short | Glucocorticoids modify intracranial pressure in freely moving rats |
| title_sort | glucocorticoids modify intracranial pressure in freely moving rats |
| topic | Intracranial pressure Glucocorticoid Prednisolone Corticosterone Choroid plexus |
| url | https://doi.org/10.1186/s12987-023-00439-y |
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