Ouabain in Pseudotumor Cerebri
Northern Neurosciences, Inc.
BACKGROUND: Pseudotumor cerebri (PTC) is a disorder of elevated pressure within the brain of unknown cause. Symptomatically, PTC causes headache and visual obscurations, and may lead to blindness from optic nerve atrophy. PTC is related to an overproduction of cerebrospinal fluid. Risk factors for idiopathic PTC include steroid use or withdrawal, adrenal failure, fat-soluble vitamin use, and menstrual irregularities. The characteristics of the idiopathic PTC patient and the aforementioned risk factors for PTC often involve abnormal steroid production or interfere with the normal activity of steroids.
One steroid that may underlie idiopathic PTC is ouabain. Ouabain is a naturally occurring plant steroid that has subsequently been found in mammalian tissues including brain. Ouabain is similar to the drug digoxin in that it acts to potently inhibit the activity of the sodium-potassium ATPase enzyme. Since sodium-potassium ATPase activity is known to be the limiting factor in the production of cerebrospinal fluid, endogenous ouabain may serve to limit the production of this fluid thereby preventing an increase in pressure within the brain. Conversely, loss of endogenous ouabain may increase the production of cerebrospinal fluid, which would then increase the pressure within the brain. In support of such a mechanism, administration of ouabain into the brains of cats has been shown to reduce cerebrospinal fluid production, and digoxin historically had been the treatment-of-choice for PTC until the advent of carbonic anhydrase inhibitors.
HYPOTHESIS: We hypothesize that in idiopathic PTC patients, the level of ouabain will be lower in cerebrospinal fluid and blood than it will be in patients with other neurological diseases.
METHODS: We propose to analyze the cerebrospinal fluid and blood of PTC patients for the level of endogenous ouabain. Cerebrospinal fluid will be taken by lumbar puncture. Blood samples will be drawn by venipuncture. We will compare the ouabain level in idiopathic PTC patients against those from patients with other types of neurological diseases who are also subject to lumbar puncture (‘control’ patients). Ouabain will be measured in cerebrospinal fluid and blood samples by means of an established radioimmunoassay for ouabain; these services will be provided free-of-charge by a collaborating laboratory. Exclusion criteria will be current use of the drug digoxin or similar compounds.
For Researchers
Other Active Projects
