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Choroid plexus aquaporin 1 and intracranial pressure are increased in obese rats: towards an idiopathic intracranial hypertension model?

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Abstract

Background/Objectives:

Idiopathic intracranial hypertension (IIH) is a condition of increased intracranial pressure (ICP) without identifiable cause. The majority of IIH patients are obese, which suggests a connection between ICP and obesity. The aim of the study was to compare ICP in lean and obese rats. We also aimed to clarify if any ICP difference could be attributed to changes in some well-known ICP modulators; retinol and arterial partial pressure of CO2 (pCO2). Another potential explanation could be differences in water transport across the choroid plexus (CP) epithelia, and thus we furthermore investigated expression profiles of aquaporin 1 (AQP1) and Na/K ATPase.

Methods:

ICP was measured in obese and lean Zucker rats over a period of 28 days. Arterial pCO2 and serum retinol were measured in serum samples. The CPs were isolated, and target messenger RNA (mRNA) and protein were analyzed by quantitative PCR and western blot, respectively.

Results:

Obese rats had elevated ICP compared to lean controls on all recording days except day 0 (P<0.001). Serum retinol (P=0.35) and arterial pCO2 (P=0.16) did not differ between the two groups. Both AQP1 mRNA and protein levels were increased in the CP of the obese rats compared to lean rats (P=0.0422 and P=0.0281). There was no difference in Na/K ATPase mRNA or protein levels (P=0.2688 and P=0.1304).

Conclusion:

Obese Zucker rats display intracranial hypertension and increased AQP1 expression in CP compared to lean controls. The mechanisms behind these changes are still unknown, but appear to be unrelated to altered pCO2 levels or retinol metabolism. This indicates that the increase in ICP might be related to increased AQP1 levels in CP. Although further studies are warranted, obese Zucker rats could potentially model some aspects of the IIH pathophysiology.

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References

  1. Friedman DI, Jacobson DM . Idiopathic intracranial hypertension. J Neuroophthalmol 2004; 24: 138–145.

    Article  Google Scholar 

  2. Markey KA, Mollan SP, Jensen RH, Sinclair AJ . Understanding idiopathic intracranial hypertension: mechanisms, management, and future directions. Lancet Neurol 2016; 15: 78–91.

    Article  Google Scholar 

  3. Sinclair AJ, Burdon MA, Nightingale PG, Ball AK, Good P, Matthews TD et al. Low energy diet and intracranial pressure in women with idiopathic intracranial hypertension: prospective cohort study. BMJ 2010; 341: c2701.

    Article  Google Scholar 

  4. Skau M, Sander B, Milea D, Jensen R . Disease activity in idiopathic intracranial hypertension: a 3-month follow-up study. J Neurol 2011; 258: 277–283.

    Article  Google Scholar 

  5. Sugerman HJ, Felton WL 3rd, Salvant JB Jr., Sismanis A, Kellum JM . Effects of surgically induced weight loss on idiopathic intracranial hypertension in morbid obesity. Neurology 1995; 45: 1655–1659.

    Article  CAS  Google Scholar 

  6. Wong R, Madill SA, Pandey P, Riordan-Eva P . Idiopathic intracranial hypertension: the association between weight loss and the requirement for systemic treatment. BMC Ophthalmol 2007; 7: 15.

    Article  Google Scholar 

  7. Warner JEA, Larson AJ, Bhosale P, Digre KB, Henley C, Alder SC et al. Retinol-binding protein and retinol analysis in cerebrospinal fluid and serum of patients with and without idiopathic intracranial hypertension. J Neuroophthalmol 2007; 27: 258–262.

    Article  Google Scholar 

  8. Warner JE, Bernstein PS, Yemelyanov A, Alder SC, Farnsworth ST, Digre KB . Vitamin A in the cerebrospinal fluid of patients with and without idiopathic intracranial hypertension. Ann Neurol 2002; 52: 647–650.

    Article  CAS  Google Scholar 

  9. Tabassi A, Salmasi AH, Jalali M . Serum and CSF vitamin A concentrations in idiopathic intracranial hypertension. Neurology 2005; 64: 1893–1896.

    Article  CAS  Google Scholar 

  10. Selhorst JB, Kulkantrakorn K, Corbett JJ, Leira EC, Chung SM . Retinol-binding protein in idiopathic intracranial hypertension (IIH). J Neuroophthalmol 2000; 20: 250–252.

    Article  CAS  Google Scholar 

  11. Jacobson DM, Berg R, Wall M, Digre KB, Corbett JJ, Ellefson RD . Serum vitamin A concentration is elevated in idiopathic intracranial hypertension. Neurology 1999; 53: 1114–1118.

    Article  CAS  Google Scholar 

  12. Fishman RA . Polar bear liver, vitamin A, aquaporins, and pseudotumor cerebri. Ann Neurol 2002; 52: 531–533.

    Article  Google Scholar 

  13. el Ouahabi A, Lorenzo AV, Black PM . Study of pseudotumor cerebri in vitamin A deficient rabbit. Eur J Pediatr Surg 1992; 2 (Suppl 1): 43–44.

    PubMed  Google Scholar 

  14. Maddux GW, Foltz FM, Nelson SR . Effect of vitamin A intoxication on intracranial pressure and brain water in rats. J Nutr 1974; 104: 478–482.

    Article  CAS  Google Scholar 

  15. Corey JE, Hayes KC . Cerebrospinal fluid pressure, growth, and hematology in relation to retinal status of the rat in acute vitamin A deficiency. J Nutr 1972; 102: 1585–1593.

    Article  CAS  Google Scholar 

  16. Kuenzel WJ, Rowland AM, Pillai PB, O'Connor-Dennie TI, Emmert JL, Wideman RF . The use of vitamin A-deficient diets and jugular vein ligation to increase intracranial pressure in chickens (Gallus gallus. Poult Sci 2006; 85: 537–545.

    Article  CAS  Google Scholar 

  17. Stiebel-Kalish H, Eyal S, Steiner I . The role of aquaporin-1 in idiopathic and drug-induced intracranial hypertension. Med Hypotheses 2013; 81: 1059–1062.

    Article  CAS  Google Scholar 

  18. Damkier HH, Brown PD, Praetorius J . Cerebrospinal fluid secretion by the choroid plexus. Physiol Rev 2013; 93: 1847–1892.

    Article  CAS  Google Scholar 

  19. Zhang YY, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM . Positional cloning of the mouse obese gene and its human homolog. Nature 1994; 372: 425–432.

    Article  CAS  Google Scholar 

  20. Chua SC, White DW, WuPeng XS, Liu SM, Okada N, Kershaw EE et al. Phenotype of fatty due to Gln269Pro mutation in the leptin receptor (Lepr). Diabetes 1996; 45: 1141–1143.

    Article  CAS  Google Scholar 

  21. Chua SC Jr., Chung WK, Wu-Peng XS, Zhang Y, Liu SM, Tartaglia L et al. Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor. Science 1996; 271: 994–996.

    Article  CAS  Google Scholar 

  22. Uldall M, Juhler M, Skjolding AD, Kruuse C, Jansen-Olesen I, Jensen R . A novel method for long-term monitoring of intracranial pressure in rats. J Neurosci Methods 2014; 227: 1–9.

    Article  Google Scholar 

  23. Gevers EF, Wit JM, Robinson IC . Effects of long-term gonadotrophin-releasing hormone analog treatment on growth, growth hormone (GH) secretion, GH receptors, and GH-binding protein in the rat. Pediatr Res 1998; 43: 111–120.

    Article  CAS  Google Scholar 

  24. Arakaki X, McCleary P, Techy M, Chiang J, Kuo L, Fonteh AN et al. Na,K-ATPase alpha isoforms at the blood-cerebrospinal fluid-trigeminal nerve and blood-retina interfaces in the rat. Fluids Barriers CNS 2013; 10: 14.

    Article  CAS  Google Scholar 

  25. Deborah I, Friedman PI, Crabtree P Comparison of Intracranial Pressure in Zucker Fatty Rats and Sprague-Dawley Rats. North American Neuro-Ophthalmology Society Annual Meeting #23, 1997. Poster presentation, 10 (session 2).

  26. Delamere NA, Tamiya S . Expression, regulation and function of Na,K-ATPase in the lens. Prog Retin Eye Res 2004; 23: 593–615.

    Article  CAS  Google Scholar 

  27. van Hulst RA, Hasan D, Lachmann B . Intracranial pressure, brain PCO2, PO2, and pH during hypo- and hyperventilation at constant mean airway pressure in pigs. Intensive Care Med 2002; 28: 68–73.

    Article  Google Scholar 

  28. Brian JE Jr . Carbon dioxide and the cerebral circulation. Anesthesiology 1998; 88: 1365–1386.

    Article  Google Scholar 

  29. Zhou W, Liu W . Hypercapnia and hypocapnia in neonates. World J Pediatr 2008; 4: 192–196.

    Article  Google Scholar 

  30. Dennis LJ, Mayer SA . Diagnosis and management of increased intracranial pressure. Neurol India 2001; 49 (Suppl 1): S37–S50.

    PubMed  Google Scholar 

  31. Osmond JM, Mintz JD, Stepp DW . Preventing increased blood pressure in the obese Zucker rat improves severity of stroke. Am J Physiol Heart Circ Physiol 2010; 299: H55–H61.

    Article  CAS  Google Scholar 

  32. Institoris A, Snipes JA, Katakam PV, Domoki F, Boda K, Bari F et al. Impaired vascular responses of insulin-resistant rats after mild subarachnoid hemorrhage. Am J Physiol Heart Circ Physiol 2011; 300: H2080–H2087.

    Article  CAS  Google Scholar 

  33. Bouma GJ, Muizelaar JP, Bandoh K, Marmarou A . Blood pressure and intracranial pressure-volume dynamics in severe head injury: relationship with cerebral blood flow. J Neurosurg 1992; 77: 15–19.

    Article  CAS  Google Scholar 

  34. Lilja A, Andresen M, Hadi A, Christoffersen D, Juhler M . Clinical experience with telemetric intracranial pressure monitoring in a Danish neurosurgical center. Clin Neurol Neurosurg 2014; 120: 36–40.

    Article  Google Scholar 

  35. Headache Classification Committee of the International Headache Society (IHS).. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 2013; 33: 629–808.

    Article  Google Scholar 

  36. Rangel-Castilla L, Gopinath S, Robertson CS . Management of intracranial hypertension. Neurol Clin 2008; 26: 521–541, x.

    Article  Google Scholar 

  37. Dunn LT . Raised intracranial pressure. J Neurol Neurosurg Psychiatry 2002; 73 (Suppl 1): i23–i27.

    Article  Google Scholar 

  38. Brosche TM . Intracranial pressure and cerebral perfusion pressure ranges. Crit Care Nurse 2011; 31: 18–19 author's reply 9.

    Article  Google Scholar 

  39. Andresen M, Juhler M . Intracranial pressure following complete removal of a small demarcated brain tumor: a model for normal intracranial pressure in humans. J Neurosurg 2014; 121: 797–801.

    Article  Google Scholar 

  40. Fellmann L, Nascimento AR, Tibirica E, Bousquet P . Murine models for pharmacological studies of the metabolic syndrome. Pharmacol Ther 2013; 137: 331–340.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The current study was funded by the University of Copenhagen, The Research Foundation of The Capital Region, The A.P Møller Foundation for the Advancement of Medical Science, Aase and Ejnar Danielsen Foundation, and Foundation for Research in Neurology.

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Authors and Affiliations

  1. Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, University of Copenhagen, Glostrup, Denmark

    M Uldall, D K Bhatt, I Jansen-Olesen & R H Jensen

  2. Glostrup Research Institute, Rigshospitalet Glostrup, University of Copenhagen, Glostrup, Denmark

    M Uldall, D K Bhatt & I Jansen-Olesen

  3. Department of Neurology, Neurovascular Research Unit, Herlev Hospital, University of Copenhagen, Herlev, Denmark

    C Kruuse

  4. Department of Neurosurgery, Rigshospitalet Blegdamsvej, University of Copenhagen, Copenhagen, Denmark

    M Juhler

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  1. M Uldall
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  2. D K Bhatt
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  3. C Kruuse
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  4. M Juhler
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  5. I Jansen-Olesen
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  6. R H Jensen
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Correspondence to R H Jensen.

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Uldall, M., Bhatt, D., Kruuse, C. et al. Choroid plexus aquaporin 1 and intracranial pressure are increased in obese rats: towards an idiopathic intracranial hypertension model?. Int J Obes 41, 1141–1147 (2017). https://doi.org/10.1038/ijo.2017.83

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  • DOI: https://doi.org/10.1038/ijo.2017.83

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