@article{83d169846c664e7c9321ccaa22d86ffc,
title = "Preclinical Development of a Prophylactic Neuroprotective Therapy for the Preventive Treatment of Anticipated Ischemia-Reperfusion Injury",
abstract = "Ischemia-reperfusion brain injury can be iatrogenically induced secondary to life-saving procedures. Prophylactic treatment of these patients offers a promising prevention for lifelong complications. We postulate that a cytosine-guanine (CpG) oligodeoxynucleotide (ODN) can provide robust antecedent protection against cerebral ischemic injury with minimal release of pro-inflammatory cytokines, making it an ideal candidate for further clinical development. Mouse and nonhuman primate (NHP) models of cerebral ischemic injury were used to test whether an A-type CpG ODN, which induces minimal systemic inflammatory cytokine responses, can provide prophylactic protection. Extent of injury in the mouse was measured by histological staining of live tissue. In the NHP, injury was assessed 2 and 7 days post-occlusion from T2-weighted magnetic resonance images and neurological and motor deficits were cataloged daily. Plasma cytokine levels were measured using species-specific Luminex assays. Prophylactic administration of an A-type CpG ODN provided robust protection against cerebral ischemic injury in the mouse with minimal systemic inflammation. Rhesus macaques treated with D192935, a mixture of human optimized A-type CpG ODNs, had smaller infarcts and demonstrated significantly less neurological and motor deficits following ischemic injury. Our findings demonstrate the translational potential of D192935 as a prophylactic treatment for patients at risk of cerebral ischemic injury.",
keywords = "CpG ODN, Ischemia, Neuroprotection, Nonhuman primate, Preconditioning, Stroke",
author = "Bahjat, {Frances Rena} and {Alexander West}, G. and Kohama, {Steven G.} and Christine Glynn and Urbanski, {Henryk F.} and Hobbs, {Theodore R.} and Eric Earl and Stevens, {Susan L.} and Stenzel-Poore, {Mary P.}",
note = "Funding Information: We thank Laurie Renner for support with behavioral assessments and animal handling and Dr. Jessica Minnier for statistical support. The authors would like to thank Sara Christensen and Valerie Conrad for excellent technical support in the mouse studies and Dr. Mingyue Liu for the mouse middle cerebral artery occlusion (MCAO) surgeries. This work was supported by National Institutes of Health grants NS064953 (HFU, MSP, SGK), NS062381 (MSP) and OD011092 (HFU, SGK). This work was supported by National Institutes of Health grants NS064953 (HFU, MSP, SGK); NS062381 (MSP); and OD011092 (HFU, SGK). Frances Rena Bahjat declares that she has no conflict of interest. G. Alexander West declares that he has no conflict of interest. Steven Kohama declares that he has no conflict of interest. Christine Glynn declares that she has no conflict of interest. Henryk Urbanski declares that he has no conflict of interest. Theodore Hobbs declares that he has no conflict of interest. Eric Earl declares that he has no conflict of interest. Susan Stevens declares that she has no conflict of interest. Mary Stenzel-Poore declares that she has no conflict of interest. Funding Information: We thank Laurie Renner for support with behavioral assessments and animal handling and Dr. Jessica Minnier for statistical support. The authors would like to thank Sara Christensen and Valerie Conrad for excellent technical support in the mouse studies and Dr. Mingyue Liu for the mouse middle cerebral artery occlusion (MCAO) surgeries. This work was supported by National Institutes of Health grants NS064953 (HFU, MSP, SGK), NS062381 (MSP) and OD011092 (HFU, SGK). Funding Information: This work was supported by National Institutes of Health grants NS064953 (HFU, MSP, SGK); NS062381 (MSP); and OD011092 (HFU, SGK). Publisher Copyright: {\textcopyright} 2017, Springer Science+Business Media New York.",
year = "2017",
month = aug,
day = "1",
doi = "10.1007/s12975-017-0532-8",
language = "English (US)",
volume = "8",
pages = "322--333",
journal = "Translational Stroke Research",
issn = "1868-4483",
publisher = "Springer US",
number = "4",
}