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S. Rauz, E.A. Walker, J.W. Tomlinson, S.V. Hughes, P.J. Wood, P.M. Stewart, P.I. Murray; Cerebrospinal Fluid Production – A Role For 11ß–Hydroxysteroid Dehydrogenase Type 1? . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4679.
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Purpose:Cerebrospinal fluid (CSF) fills the ventricles and the subarachnoid space. Approximately 50–75% of the CSF is produced by the epithelial cells of the choroid plexus (CP) draining through the arachnoid villi primarily into the venous sinuses. The circulation of CSF is essential for normal cerebral and optic nerve function, and protects the intracranial tissues from mechanical trauma. The secretion of sodium and anions by the CP creates an osmotic gradient driving the movement of water into the ventricles, analogous to the mechanisms involved in aqueous humour production by the ocular ciliary epithelium. We have shown that 11beta–hydroxysteroid dehydrogenase type 1 (11ß–HSD1), by activating cortisol (F) from cortisone (E) in the ocular ciliary epithelium, is a novel mediator of aqueous production. As elevated CSF F levels are found with increasing age, in post–menopausal women, Alzheimers disease, and multiple sclerosis, this study was designed to assess whether corticosteroid mechanisms were involved CSF production. Methods:Using an animal model, CSF and venous blood was collected from New Zealand White Albino Rabbits (NZWAR) for quantification of F and E by radioimmunoassay. Oxo–reductase (E to F) and dehydrogenase (F to E) activity was assessed by enzyme assays performed on dissected CP tissue. 11ß–HSD1 expression was also evaluated by immunohistochemistry on 3µm sections of formalin–fixed, paraffin embedded CP. Results:Radioimmunoassay of CSF and serum revealed an F:E ratio of 22.4 and 11.3 respectively, while enzyme assays confirmed predominant oxo–reductase (E to F) activity. Immunolocalisation confirmed 11ß–HSD1 expression in the CP. Conclusions:These data define the presence of an 11ß–HSD1 regulated cortisol generating system within the CP epithelial cells of the NZWAR suggesting a role in CSF production. Aberrant expression of this enzyme could represent an underlying mechanism for optic nerve or neuroendocrine disease processes.
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