Cerebral Oxidation of Fumarate-2-C¹⁴ in Normal Human Subjects

¹ From the Research Department, Albert Einstein Medical Center, Philadelphia, Pennsylvania

The total activity of labeled carbon dioxide in the blood entering and leaving the brain was determined following a single injection of fumarate-2-C¹⁴ in four normal human subjects. Blood samples were drawn simultaneously from the femoral artery and the superior bulb of the internal jugular vein. Also, cerebrospinal fluid specimens were collected. Evidence from these experiments and from others in which labeled bicarbonate was given as a single injection to four other normal human subjects indicated that the brain had produced significant quantities of C¹⁴O₂ and that there was an immediate formation of C¹⁴O₂ by the brain after injection of the isotope. Labeled fumarate was designated as the most probable source of the cerebral C¹⁴O₂ for the following reason: an immediate formation of labeled CO₂ by the brain would have required an immediate concentration of labeled substrate in the brain. Determinations of radioactivity of blood filtrate and of fumarate, glucose and pyruvate isolated from it showed that only labeled fumarate was taken up by the brain immediately after injection of fumarate-2-C¹⁴. An estimate of the fraction of the cumulative C¹⁴O₂ resulting from the oxidation of the labeled fumarate by the brain showed that an average of 2.8% of the injected C¹⁴ was converted into C¹⁴O₂ after about 80 minutes. C¹⁴O₂ and some traces of fumarate activity were also observed in cerebrospinal fluid specimens; however, the importance of these latter findings is not known. The question of a re-evaluation of present concepts of blood-brain barrier was raised.