Glucocorticoids modify intracranial pressure in freely moving rats
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Glucocorticoids modify intracranial pressure in freely moving rats. / Westgate, Connar Stanley James; Israelsen, Ida Marchen Egerod; Kamp-Jensen, Christina; Jensen, Rigmor Højland; Eftekhari, Sajedeh.
In: Fluids and Barriers of the CNS, Vol. 20, 35, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Glucocorticoids modify intracranial pressure in freely moving rats
AU - Westgate, Connar Stanley James
AU - Israelsen, Ida Marchen Egerod
AU - Kamp-Jensen, Christina
AU - Jensen, Rigmor Højland
AU - Eftekhari, Sajedeh
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Choroid plexus
KW - Corticosterone
KW - Glucocorticoid
KW - Intracranial pressure
KW - Prednisolone
U2 - 10.1186/s12987-023-00439-y
DO - 10.1186/s12987-023-00439-y
M3 - Journal article
C2 - 37231507
AN - SCOPUS:85160231757
VL - 20
JO - Fluids and Barriers of the CNS
JF - Fluids and Barriers of the CNS
SN - 2045-8118
M1 - 35
ER -
ID: 370577732