PT  - JOURNAL ARTICLE
AU  - Connar Stanley James Westgate
AU  - Snorre Malm Hagen
AU  - Ida Marchen Egerod Israelsen
AU  - Steffen Hamann
AU  - Rigmor Højland Jensen
AU  - Sajedeh Eftekhari
TI  - Translational modeling of non-traumatic raised intracranial pressure in rodents; the impact of diet-induced obesity on cephalic hypersensitivity and retinal degeneration
AID  - 10.1101/2021.08.05.455266
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.08.05.455266
4099  - http://biorxiv.org/content/early/2021/08/06/2021.08.05.455266.short
4100  - http://biorxiv.org/content/early/2021/08/06/2021.08.05.455266.full
AB  - Elevated intracranial pressure (ICP) is a feature of critical cerebral disorders. Obesity has been linked to raised ICP, and especially to disorders such as idiopathic intracranial pressure (IIH). We aimed to explore the impact of diet-induced obesity (DIO) on ICP, cephalic sensitivity and structural retinal changes with the dual goal of developing a disease model for non-traumatic raised ICP and IIH. Rats were fed high-fat diet or matched control diet. To assess pain sensitivity, Von Frey and light/dark box testing were performed. Dual energy x-ray absorptiometry scanning was used to measure body composition. Optic nerve head and retinal structures were evaluated using optical coherence tomography. Intraocular pressure was assessed. Rats were then implanted with telemetric device for continuous ICP recording. At the end, eye histology and molecular analysis on choroid plexus (CP) and trigeminal ganglion (TG) were performed. The DIO rats had double the abdominal fat mass. ICP was 55% higher in obese rats (p=0.003). Altered pain thresholds were found in DIO rats as denoted by a lower periorbital threshold (p=0.0002). Expression of Calca and Trpv1 was elevated in TG. Furthermore, a peripapillary retinal nerve fiber layer swelling (p=0.0026) with subsequent neuroretinal degeneration p=0.02) was detected in DIO rats. There was a trend to increased expression of AQP1 and NKCC1 at CP. This study demonstrates for the first time that DIO leads to raised ICP, with clinically relevant sequalae. Our novel model for non-traumatic raised ICP could expand the knowledge regarding disorders with elevated ICP and IIH.Competing Interest StatementThe authors have declared no competing interest.AQP1aquaporin 1CDcontrol dietCGRPcalcitonin gene related peptideCPchoroid plexusCSFcerebrospinal fluidDIODiet induced obesityFMfat massGCglucocorticoidsHFDhigh fat dietICPIntracranial pressureIIHIdiopathic intracranial hypertensionIOPIntraocular pressureLMlean massmmHgmillimeters of mercuryNKCC1Na+-K+-2Cl--1 cotransporterOCToptical coherence tomographyRNFBretinal nerve fiber bundleRNFLrentinal nerve fiber layerTBItraumatic brain injuryTGtrigeminal ganglionTRPV1transient receptor potential vanilloid subfamily member 1