Introduction During the past half century, aniline dyes and fluorescent compounds have been used to study alterations in the blood-brain barrier occurring in a variety of neuropathological conditions. Theories that were evolved to explain the absence of staining of the normal brain by acid dyes included: the impermeability of cerebrovascular endothelium to negatively charged particles, 1 a lack of brain tissue affinity for dyes, 2 and a barrier imposed by ground substance. 3 Although the binding of certain acid and basic dyes to protein had been studied in some detail by chemists, 4 there was no attempt in the early neurological literature to relate exclusion of dye from brain to protein impermeability. The importance of binding to plasma protein as a mechanism limiting dye penetration into brain was first emphasized by Tschirgi. 5 More recently, Clasen et al 6 have demonstrated a quantitative relationship between the brain uptake of Evans
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Cutler et al. (1964) studied this question.
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