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Translational Stroke Research
Published in: Translational Stroke Research 4/2017

01-08-2017 | Original Article

Preclinical Development of a Prophylactic Neuroprotective Therapy for the Preventive Treatment of Anticipated Ischemia-Reperfusion Injury

Published in: Translational Stroke Research | Issue 4/2017

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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.

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Metadata
Title
Preclinical Development of a Prophylactic Neuroprotective Therapy for the Preventive Treatment of Anticipated Ischemia-Reperfusion Injury
Publication date
01-08-2017
Published in
Translational Stroke Research / Issue 4/2017
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-017-0532-8

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