Toll-like receptor agonists as antecedent therapy for ischemic brain injury: Advancing preclinical studies to the nonhuman primate

Frances Bahjat, Keri B. Vartanian, G. Alexander West, Mary Stenzel-Poore

Research output: Chapter in Book/Report/Conference proceedingChapter

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

Original languageEnglish (US)
Title of host publicationTranslational Stroke Research
Subtitle of host publicationFrom Target Selection to Clinical Trials
PublisherSpringer New York
Pages205-230
Number of pages26
ISBN (Electronic)9781441995308
ISBN (Print)9781441995292
DOIs
Publication statusPublished - Jan 1 2012

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ASJC Scopus subject areas

  • Medicine(all)
  • Neuroscience(all)

Cite this

Bahjat, F., Vartanian, K. B., West, G. A., & Stenzel-Poore, M. (2012). Toll-like receptor agonists as antecedent therapy for ischemic brain injury: Advancing preclinical studies to the nonhuman primate. In Translational Stroke Research: From Target Selection to Clinical Trials (pp. 205-230). Springer New York. https://doi.org/10.1007/978-1-4419-9530-8_10