Jonathan Wardman

Assistant Professor, MacAulay Lab

Titel: Obesity in female rats does not cause idiopathic intracranial hypertension –are secondary factors required?

Abstract: Introduction: Idiopathic Intracranial Hypertension (IIH) is a condition characterized by increased intracranial pressure (ICP), impaired vision and headache, but with unresolved etiology. IIH occurs predominantly in obese (body mass index (BMI) ≥30) women of childbearing age, though age, BMI and female sex do not encompass all aspects of IIH pathophysiology. Female IIH patients show a distinct hormonal profile, highlighted by androgen excess. To reveal the etiology of IIH, we modelled female obesity in rats.

Methods: Rats genetically lacking the leptin receptor, Zucker rats, were grown to obesity (mimicking hBMI of 46) and their ICP, brain water content, ventricular morphology, cerebrospinal fluid (CSF) production, and choroidal transcriptomic profile assessed in comparison to their lean counterparts (hBMI 23). The IIH-related androgen excess was mimicked by bi-weekly testosterone injections (4 weeks) of female Wistar rats followed by determination of their brain water content, CSF production, and choroidal transport activity.

Results: Obesity did not, on its own, create the elevated ICP characteristic of IIH, not did it alter various aspects of brain fluid dynamics or the choroidal transportome. Testosterone treatment, on the other hand, caused elevated CSF production due to increased activity of the NKCC1 transport protein.

Conclusions: These data indicate that while obesity and female sex are characteristic of IIH, these physiological aspects do not alone establish IIH pathophysiology, and that the IIH-related androgen excess may be crucial in IIH etiology. Future studies establishing an IIH animal model might require the combination of these, and possibly other, features.