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Therapeutic Intranasal Delivery for Stroke and Neurological Disorders pp 101–115Cite as

Intranasal tPA Application for Axonal Remodeling in Rodent Stroke and Traumatic Brain Injury Models

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

Abstract

Stroke and traumatic brain injury (TBI) are the major causes of adult long-term disability worldwide. Unfortunately, there are no efficacious therapies available for the vast majority of stroke and TBI patients during their convalescence. As a thrombolytic agent, recombinant tissue plasminogen activator (tPA) is the only FDA approved therapeutic agent for treatment of acute ischemic stroke; however, the application of tPA is limited by the narrow therapeutic time window and potential adverse side effects on brain edema and hemorrhage. In addition to vascular endothelium derived tPA in the circulation, neuroendocrine tissue synthesized tPA is widely distributed in the CNS and is involved in axonal path finding, synaptic plasticity and dendritic remodeling during development, and axonal outgrowth after stroke and injury. We have investigated the therapeutic effect of tPA on neurological recovery and corticospinal axonal remodeling in rodent subacute stroke and TBI models administered intranasally, to bypass the blood-brain barrier and avoid the rapid inactivation and clearance of tPA in the circulation. The neurorestorative benefits of tPA in subacute stroke and TBI treatments and the potential underlying mechanisms are discussed in this chapter.

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Authors and Affiliations

  1. Department of Neurology, Henry Ford Hospital, Detroit, MI, USA

    Zhongwu Liu & Michael Chopp

  2. Department of Neurosurgery, Henry Ford Hospital, Detroit, MI, USA

    Ye Xiong

  3. Department of Physics, Oakland University, Rochester, MI, USA

    Michael Chopp

Authors
  1. Zhongwu Liu
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  2. Ye Xiong
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  3. Michael Chopp
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Correspondence to Zhongwu Liu .

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Editors and Affiliations

  1. Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA

    Jun Chen

  2. Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jian Wang

  3. Departments of Anesthesiology and Neurology, Emory University School of Medicine, Atlanta, GA, USA

    Ling Wei

  4. Department of Physiology, Loma Linda University School of Medicine, Loma Linda, CA, USA

    John H. Zhang

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Liu, Z., Xiong, Y., Chopp, M. (2019). Intranasal tPA Application for Axonal Remodeling in Rodent Stroke and Traumatic Brain Injury Models. In: Chen, J., Wang, J., Wei, L., Zhang, J. (eds) Therapeutic Intranasal Delivery for Stroke and Neurological Disorders. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-030-16715-8_9

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  • DOI: https://doi.org/10.1007/978-3-030-16715-8_9

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