Proof of concept: Pharmacological preconditioning with a Toll-like receptor agonist protects against cerebrovascular injury in a primate model of stroke

Frances Rena Bahjat, Rebecca L. Williams-Karnesky, Steven G. Kohama, G. Alexander West, Kristian Doyle, Maxwell D. Spector, Theodore R. Hobbs, Mary P. Stenzel-Poore

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Cerebral ischemic injury is a significant portion of the burden of disease in developed countries; rates of mortality are high and the costs associated with morbidity are enormous. Recent therapeutic approaches have aimed at mitigating the extent of damage and/or promoting repair once injury has occurred. Often, patients at high risk of ischemic injury can be identified in advance and targeted for antecedent neuroprotective therapy. Agents that stimulate the innate pattern recognition receptor, Toll-like receptor 9, have been shown to induce tolerance (precondition) to ischemic brain injury in a mouse model of stroke. Here, we demonstrate for the first time that pharmacological preconditioning against cerebrovascular ischemic injury is also possible in a nonhuman primate model of stroke in the rhesus macaque. The model of stroke used is a minimally invasive transient vascular occlusion, resulting in brain damage that is primarily localized to the cortex and as such, represents a model with substantial clinical relevance. Finally, K-type (also referred to as B-type) cytosine-guanine-rich DNA oligonucleotides, the class of agents employed in this study, are currently in use in human clinical trials, underscoring the feasibility of this treatment in patients at risk of cerebral ischemia.

Original languageEnglish (US)
Pages (from-to)1229-1242
Number of pages14
JournalJournal of Cerebral Blood Flow and Metabolism
Volume31
Issue number5
DOIs
StatePublished - May 2011
Externally publishedYes

Fingerprint

Toll-Like Receptors
Primates
Stroke
Wounds and Injuries
Toll-Like Receptor 9
Pattern Recognition Receptors
Cytosine
Guanine
Brain Ischemia
Macaca mulatta
Developed Countries
Oligonucleotides
Brain Injuries
Blood Vessels
Therapeutics
Clinical Trials
Pharmacology
Morbidity
Costs and Cost Analysis
Mortality

Keywords

  • CpG ODN
  • ischemia
  • neuroprotection
  • nonhuman primate
  • stroke
  • Toll-like receptors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology
  • Medicine(all)

Cite this

Proof of concept : Pharmacological preconditioning with a Toll-like receptor agonist protects against cerebrovascular injury in a primate model of stroke. / Bahjat, Frances Rena; Williams-Karnesky, Rebecca L.; Kohama, Steven G.; West, G. Alexander; Doyle, Kristian; Spector, Maxwell D.; Hobbs, Theodore R.; Stenzel-Poore, Mary P.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 31, No. 5, 05.2011, p. 1229-1242.

Research output: Contribution to journalArticle

Bahjat, Frances Rena ; Williams-Karnesky, Rebecca L. ; Kohama, Steven G. ; West, G. Alexander ; Doyle, Kristian ; Spector, Maxwell D. ; Hobbs, Theodore R. ; Stenzel-Poore, Mary P. / Proof of concept : Pharmacological preconditioning with a Toll-like receptor agonist protects against cerebrovascular injury in a primate model of stroke. In: Journal of Cerebral Blood Flow and Metabolism. 2011 ; Vol. 31, No. 5. pp. 1229-1242.
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