The effect of hypercapnia on the blood-brain barrier to sucrose in the rabbit.

It has been stated that hypercapnia increases the permeability of the bloodbrain barrier to several compounds, e.g., trypan blue,' sulphate2 and iodinated serum albumin."' The experiments just cited have shown that during hypercapnia more of the substance under study has passed from blood into the brain tissue than in control animals, but such an effect could have been due to the expansion of the extracellular space rather than to an increased rate of penetration into a constant space. In the present work, this difficulty in interpretation has been avoided by presenting the solute first by way of the blood and, in a further series of experiments, by way of the cerebrospinal fluid. The solute chosen was 14C-labelled sucrose, which is probably mainly, if not entirely, confined to the extracellular space. If there is, indeed, a specific effect of the hypercapnia on the rate of passage of sucrose out of the blood into the brain, then the amounts passing in given time intervals should be greater than in control animals when a constant level is maintained in the blood. On the other hand, when a constant level is maintained in the cerebrospinal fluid, by ventriculo-cisternal perfusion, hypercapnia should cause no increase in uptake by brain, as compared with controls; in fact it should reduce the uptake a little because of the greater losses to the blood. If the effect of hypercapnia is to increase the extracellular space, then we may expect increased uptakes when the "4C-sucrose is presented by either route, especially at the longer time intervals. It will be shown in the following that hypercapnia does, indeed, increase the permeability of the blood-brain barrier to "4C-sucrose.