History and Basic Concepts

  • Hugh Davson
  • Berislav Zloković
  • Ljubisa Rakić
  • Malcolm B. Segal


The concept of the blood-brain barrier derives from the classical studies of the pioneers in chemotherapy, such as Ehrlich, who administered dyestuffs parenterally in the hope that they would attack infective organisms. Thus Ehrlich observed that many dyes, after intravenous injection, stained the tissues of practically the whole body, while the brain was spared. Later, Lewandowsky (1900) showed that the Prussian blue reagents (iron salt and potassium ferrocyanide) did not pass from blood to brain, and he formulated clearly the concept of the blood-brain barrier (Bluthirnschranke). The more definitive demonstration of the barrier we owe to Goldmann, who showed (1909) that, after intravenous injection with trypan blue, the brain was unstained; the dye did not enter the cerebrospinal fluid (CSF), although the choroid plexuses and meninges were stained. In a second paper (Goldmann, 1913), he described experiments in which trypan blue was injected into the CSF; in this event, the brain tissue was strongly stained, so that Goldmann rightly concluded that there was, indeed, a barrier between blood, on the one hand, and brain tissue on the other. Any argument that the failure to stain the brain with trypan blue after intravenous injection was due to a peculiar staining feature of the nervous tissue was negated by this fundamental ‘second experiment’, the first experiment being the demonstration that nervous tissue was unstained after intravenous injection.


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Copyright information

© The authors 1993

Authors and Affiliations

  • Hugh Davson
    • 1
  • Berislav Zloković
    • 2
  • Ljubisa Rakić
    • 3
  • Malcolm B. Segal
    • 1
  1. 1.Sherrington School of Physiology UMDSGuy’s and St Thomas’s HospitalsLondonUK
  2. 2.USC School of MedicineLos AngelesUSA
  3. 3.School of MedicineBelgradeSerbia

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