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Blood-brain barrier unlocked

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Abstract

The brain is protected by a physiological blood-brain barrier (BBB) against toxins and some metabolites circulating in the blood. At the same time, the BBB limits penetration into the brain of many neuroactive drugs. Efficient ways to increase BBB permeability for delivery of drugs of different chemical nature into the brain are unknown. This work deals with delivery into the brain of 10−2 M dopamine, a substance that does not penetrate the BBB under normal circumstances. It was studied in two independent experiments: (i) penetration of 3H-labeled dopamine from its mixture with 10−5 M H2O2 into hypothalamus and striatum structures of intact rat brain, and (ii) effect of unlabeled dopamine from a mixture with H2O2 on the rat motor activity in a haloperidol catalepsy model. It was shown that (i) at the third minute after nasal application of the dopamine + H2O2 mixture, the dopamine level increases 45-fold in the hypothalamus and almost 30-fold in the striatum and (ii) motility of animals in the catalepsy haloperidol model is recovered 90 sec after intranasal introduction of dopamine. No such effects were observed after replacement of H2O2 by 0.9% NaCl solution. Thus, it was shown on the example of dopamine that its introduction into the nasal cavity simultaneously with H2O2 provides for rapid delivery of the drug into the brain. These results expand our knowledge concerning the biological role of exoROS in modulating BBB permeability and may contribute to the development of a new therapeutic strategy for neurological diseases.

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Abbreviations

BBB:

blood-brain barrier

DA:

dopamine

DOPAC:

3,4-dihydroxyphenylacetic acid

endoROS:

endogenous (metabolic) ROS

exoROS:

exogenous ROS

GS:

gaseous superoxide

HBO:

hyperbaric oxygenation

HPLC:

high performance liquid chromatography

MAO-A and MAO-B:

monoamine oxidase A and B-respectively

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

6-OHDA:

6-hydroxydopamine

ROS:

reactive oxygen species

SOD:

superoxide dismutase

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Authors and Affiliations

  1. Department of Human and Animal Physiology, Biological Faculty, Lomonosov Moscow State University, 119991, Moscow, Russia

    N. Goldstein, R. Goldstein & A. A. Kamensky

  2. Senior Experten Service (SES), Buschstrasse 2, 53113, Bonn, Germany

    N. Goldstein

  3. Discipline of Surgery, Faculty of Medicine, Memorial University of Newfoundland, Health Sciences Centre, 300 Prince Philip Drive, St. John’s, NL, A1B 3V6, Canada

    D. Terterov

  4. Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences, ul. Baltiiskaya 8, 125315, Moscow, Russia

    G. I. Kovalev

  5. Institute of Molecular Genetics, Russian Academy of Sciences, pl. Kurchatova 2, 123182, Moscow, Russia

    Yu. A. Zolotarev

  6. Department of Neurology and Neurosurgery, Russian State Medical University, ul. Ostrovityanova 1, 117997, Moscow, Russia

    G. N. Avakyan

  7. Department of Neurosurgery, University of California Los Angeles, 18-228 Semel, Box 957039, Los Angeles, CA, 90095-7039, USA

    S. Terterov

Authors
  1. N. Goldstein
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  2. R. Goldstein
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  3. D. Terterov
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  4. A. A. Kamensky
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  5. G. I. Kovalev
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  6. Yu. A. Zolotarev
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  7. G. N. Avakyan
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  8. S. Terterov
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Corresponding author

Correspondence to N. Goldstein.

Additional information

Original Russian Text © N. Goldstein, R. Goldstein, D. Terterov, A. A. Kamensky, G. I. Kovalev, Yu. A. Zolotarev, G. N. Avakyan, S. Terterov, 2012, published in Biokhimiya, 2012, Vol. 77, No. 5, pp. 525–532.

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Goldstein, N., Goldstein, R., Terterov, D. et al. Blood-brain barrier unlocked. Biochemistry Moscow 77, 419–424 (2012). https://doi.org/10.1134/S000629791205001X

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  • DOI: https://doi.org/10.1134/S000629791205001X

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