Further Investigations on the Blood-Brain-Barrier

Abstract

Summary and Conclusions After intravenous injection into guinea pigs weighing 300 grams all basic aniline dyes with the exception of safranine stain the brain in amounts ranging from 1 to 7 mgm. Some acid dyes (acid fuchsin, orange, bordeaux, eosin, uranine) do not stain the brain at all in the available amounts. Some others (trypan blue, congo red, water blue, alizarin blue-S, indigo di- and tetrasulphonate) stain in amounts varying from 20 to 80 mgm. The difference between basic and acid dyes is partly due to a difference in their affinity for brain tissue. The latter was tested by determining the minimal staining dose in vitro (Cv). In addition the cerebral capillaries are more permeable to basic than to acid dyes. This permeability can be determined by the ratio between the minimal staining concentrations in vivo and in vitro (CB/Cv). The permeability of the cerebral capillaries to dyes is independent of their chemical constitution, their size and their lipoid solubility. It merely depends on their electrical charge. Staphylococcus toxin acts rapidly without any incubation period. It is unable to pass the blood-brain-barrier. Staphylococcus toxin carries a negative charge at the pH of the blood. The isoelectric point is in in the neighbourhood of pH 6.2. A special method has been devised to compare the ζ-potentials of toxins. The capacity of toxins to pass the capillary system is correlated with their ζ-potentials. Tentatively, a theory is advanced according to which the selective permeability of the capillary system in general and the blood-brain-barrier in particular is due to an irreciprocal permeability.