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Barriers to Drug Delivery for Brain Trauma

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Vascular Mechanisms in CNS Trauma

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR,volume 5))

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Abstract

One of the most opposing barriers—both literally and figuratively—challenging the translational advancement of therapeutics targeting brain trauma involves effective delivery of potentially neuroprotective agents to the damaged brain. Aspects distinguishing delivery of drugs to the injured brain relative to other tissues include: (1) several unique physical features of the blood–brain barrier (BBB) vs. other blood–tissue barriers; (2) added diffusion distance associated with astrocyte swelling (in addition to interstitial edema) away from the therapeutic target; and (3) membrane transporters at both the BBB and blood–CSF barriers (BCSFB), such as ATP-binding cassette (ABC) transporters, organic anion transporters (OAT), and organic anion transporting peptides (OATP) that have the capacity to move drug substrates out of the brain, actively reducing brain bioavailability. While these “barriers” represent unique challenges to the development of efficacious neuroprotective agents for the treatment of traumatic brain injury (TBI), recent pharmacological advancements provide an optimistic outlook for designing strategies that impact outcome for victims of TBI in the near future.

We can’t go over it. We can’t go under it. Oh no! We’ve got to go through it! —Michael Rosen, We’re Going on a Bear Hunt Got to go through it to get to it —Graham Central Station, Release Yourself

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Author information

Authors and Affiliations

  1. Department of Pediatric Critical Care Medicine, Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA, 15261, USA

    Robert S. B. Clark

  2. Department of Critical Care Medicine, Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA

    F. Anthony Willyerd

  3. Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA

    Philip E. Empey

  4. Department of Critical Care Medicine and Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Patrick M. Kochanek

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  1. F. Anthony Willyerd
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  2. Philip E. Empey
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  3. Patrick M. Kochanek
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  4. Robert S. B. Clark
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Corresponding author

Correspondence to Robert S. B. Clark .

Editor information

Editors and Affiliations

  1. Departments of Neurology and Radiology, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts, USA

    Eng H. Lo

  2. Department of Pediatrics, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts, USA

    Josephine Lok

  3. Department of Neurology, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts, USA

    MingMing Ning

  4. Department of Pediatrics, Massachusetts General Hospital Harbard Medical School, Boston, Massachusetts, USA

    Michael J. Whalen

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Willyerd, F.A., Empey, P.E., Kochanek, P.M., Clark, R.S.B. (2014). Barriers to Drug Delivery for Brain Trauma. In: Lo, E., Lok, J., Ning, M., Whalen, M. (eds) Vascular Mechanisms in CNS Trauma. Springer Series in Translational Stroke Research, vol 5. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8690-9_7

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  • DOI: https://doi.org/10.1007/978-1-4614-8690-9_7

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