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Designing Drugs for Optimal Nervous System Activity

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New Concepts of a Blood—Brain Barrier

Abstract

The blood-brain barrier (BBB) continues to intrigue and frustrate neuroscientists. Perhaps like no other organ, the brain, together with its BBB challenges, the investigator at a number of levels. This is certainly true at the basic science level in elucidating the mechanisms by which it regulates the microenvironment of the central nervous system, allowing the control and transport of D-glucose, certain amino acids, ions and peptides by selective, saturable and often stereo-specific carrier systems. These systems support cerebral metabolism, neurotransmitter and protein synthesis, and maintain the extracellular environment of the brain to allow it to function under optimal conditions despite wide fluctuations in the environment of the rest of the body. The high metabolic component of the cerebral capillary endothelium, constituting the enzymatic element of the BBB, likewise interests the basic scientist in elucidating the mechanisms by which it separates and protects the brain from a variety of neurotransmitters, hormones and endogenous messengers that possess one role in the periphery and another in brain. Additionally, the manner in which the structural and enzymatic components of the BBB interact to so ably protect the brain from exogenous toxins continues to capture our attention. In as much as the BBB protects and regulates the microenvironment of the brain to allow it to function optimally under diverse conditions during health, it is frustrating from a clinical viewpoint that these same mechanisms thwart our ability to intervene during disease, impeding us in our corrective measures. Specifically, it limits our ability (i) to deliver chemotherapeutic agents, such as during the treatment of infections and cancer, and (ii) to selectively manipulate levels of neurotransmitters and neuropeptides and enzymes, such as in the treatment of Parkinson’s and Alzheimer’s diseases.

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Author information

Authors and Affiliations

  1. Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, 20892, USA

    Nigel H. Greig, Xue-Feng Pei & Timothy T. Soncrant

  2. Scientist Emeritus, National Institutes of Health, and Department of Chemistry, Georgetown University, Washington DC, 20057, USA

    Arnold Brossi

  3. Molecular Physiology and Genetics Section, Nathan W. Shock Laboratories, Gerontology Research Center, National Institute on Aging, Baltimore, MD, 21224, USA

    Donald K. Ingram

Authors
  1. Nigel H. Greig
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  2. Arnold Brossi
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  3. Xue-Feng Pei
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  4. Donald K. Ingram
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  5. Timothy T. Soncrant
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Editor information

Editors and Affiliations

  1. Institute of Ophthalmology, University College London, London, England

    John Greenwood

  2. King’s College, University of London, London, England

    David J. Begley

  3. United Medical and Dental Schools, St. Thomas’ Hospital, London, England

    Malcolm B. Segal

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© 1995 Springer Science+Business Media New York

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Greig, N.H., Brossi, A., Pei, XF., Ingram, D.K., Soncrant, T.T. (1995). Designing Drugs for Optimal Nervous System Activity. In: Greenwood, J., Begley, D.J., Segal, M.B. (eds) New Concepts of a Blood—Brain Barrier. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1054-7_25

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  • DOI: https://doi.org/10.1007/978-1-4899-1054-7_25

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