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Toll-Like Receptor Agonists as Antecedent Therapy for Ischemic Brain Injury: Advancing Preclinical Studies to the Nonhuman Primate

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Translational Stroke Research

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

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Abstract

Antecedent therapy for ischemic brain injury has the potential to protect a large, high-risk patient population from the devastating effects of cerebral ischemia associated with cardiac surgery. Substantial evidence has shown that preconditioning with a modestly damaging stimulus induces powerful endogenous neuroprotection. Pharmacological agents that stimulate toll-like receptors (TLRs) induce robust neuroprotective effects as preconditioning stimuli against cerebral ischemia in mouse and nonhuman primate models of stroke. Here we describe the progress of our preclinical development of TLR agonists as antecedent therapy against cerebral ischemic injury. The objective was to discuss studies that begin with in vitro validation in cell cultures to in vivo efficacy studies using mouse and nonhuman primate models of stroke, with particular emphasis on the TLR9 agonist CpG oligonucleotide. We provide an in-depth discussion of our novel rhesus macaque stroke model and cover the progress we have made in therapeutic testing and evaluation in these animals. These studies represent a logical path for the development of TLR agonists as antecedent therapy for the prevention of the damaging neurological complications resulting from cerebral ischemic injury.

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Author information

Authors and Affiliations

  1. Department of Molecular Microbiology and Immunology, Oregon Health and Science University, 3181 Sam Jackson Park Road, Portland, OR, 97239, USA

    Frances Rena Bahjat PhD, Keri B. Vartanian PhD & Mary P. Stenzel-Poore PhD

  2. Colorado Brain and Spine Institute, Neurotrauma Research Laboratory, Swedish Medical Center, Englewood, CO, USA

    G. Alexander West MD, PhD

  3. Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR, USA

    Mary P. Stenzel-Poore PhD

Authors
  1. Frances Rena Bahjat PhD
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  2. Keri B. Vartanian PhD
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  3. G. Alexander West MD, PhD
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  4. Mary P. Stenzel-Poore PhD
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Corresponding author

Correspondence to Mary P. Stenzel-Poore PhD .

Editor information

Editors and Affiliations

  1. , Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, 90048, California, USA

    Paul A. Lapchak

  2. Loma Linda University, 11234 Anderson Street, Room 2562B, Loma Linda, 92354, California, USA

    John H. Zhang

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Bahjat, F.R., Vartanian, K.B., West, G.A., Stenzel-Poore, M.P. (2012). Toll-Like Receptor Agonists as Antecedent Therapy for Ischemic Brain Injury: Advancing Preclinical Studies to the Nonhuman Primate. In: Lapchak, P., Zhang, J. (eds) Translational Stroke Research. Springer Series in Translational Stroke Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9530-8_10

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