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Title: Preconditioning in the Rhesus Macaque Induces a Proteomic Signature Following Cerebral Ischemia that Is Associated with Neuroprotection

Abstract

Each year thousands of patients are at risk of cerebral ischemic injury, due to iatrogenic responses to surgical procedures. Prophylactic treatment of these patients as standard care could minimize potential neurological complications. We have shown that protection of brain tissue, in a non-human primate model of cerebral ischemic injury, is possible through pharmacological preconditioning using the immune activator D192935. We postulate that preconditioning with D192935 results in neuroprotective reprogramming that is evident in the brain following experimentally induced cerebral ischemia. We performed quantitative proteomic analysis of cerebral spinal fluid (CSF) collected post-stroke from our previously published efficacy study to determine whether CSF protein profiles correlated with induced protection. Four groups of animals were examined: naïve animals (no treatment or stroke); animals treated with vehicle prior to stroke; D192935 treated and stroked animals, further delineated into two groups, ones that were protected (small infarcts) and those that were not protected (large infarcts). We found that distinct protein clusters defined the protected and non-protected animal groups, with a 16-member cluster of proteins induced exclusively in D192935 protected animals. Seventy percent of the proteins induced in the protected animals have functions that would enhance neuroprotection and tissue repair, including several members associated withmore » M2 macrophages, a macrophage phenotype shown to contribute to neuroprotection and repair during ischemic injury. Overall, these studies highlight the translational importance of CSF biomarkers in defining mechanism and monitoring responses to treatment in development of stroke therapeutics.« less

Authors:
 [1]; ORCiD logo [2];  [1]; ORCiD logo [2];  [2];  [2];  [2];  [2];  [2]; ORCiD logo [2];  [2]; ORCiD logo [2]; ORCiD logo [2];  [3];  [4];  [1];  [1]
  1. Oregon Health & Science Univ., Portland, OR (United States)
  2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  3. Houston Methodist Neurosurgery, Houston, TX (United States)
  4. Oregon National Primate Research Center, Beaverton, OR (United States)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH)
OSTI Identifier:
1571272
Report Number(s):
PNWD-SA-10567; PNNL-SA-153569
Journal ID: ISSN 1868-4483
Grant/Contract Number:  
AC05-76RL01830; NS064953; OD011092; P41GM103493
Resource Type:
Accepted Manuscript
Journal Name:
Translational Stroke Research
Additional Journal Information:
Journal Volume: 10; Journal Issue: 4; Journal ID: ISSN 1868-4483
Publisher:
Springer Science+Business Media, LLC
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; neuroprotection; non-human primates; stroke; proteomics; cerebral spinal fluid

Citation Formats

Stevens, Susan L., Liu, Tao, Bahjat, Frances Rena, Petyuk, Vladislav A., Schepmoes, Athena A., Sontag, Ryan L., Gritsenko, Marina A., Wu, Chaochao, Wang, Sheng, Shukla, Anil K., Jacobs, Jon M., Smith, Richard D., Rodland, Karin D., West, G. Alexander, Kohama, Steven G., Glynn, Christine, and Stenzel-Poore, Mary P. Preconditioning in the Rhesus Macaque Induces a Proteomic Signature Following Cerebral Ischemia that Is Associated with Neuroprotection. United States: N. p., 2018. Web. doi:10.1007/s12975-018-0670-7.
Stevens, Susan L., Liu, Tao, Bahjat, Frances Rena, Petyuk, Vladislav A., Schepmoes, Athena A., Sontag, Ryan L., Gritsenko, Marina A., Wu, Chaochao, Wang, Sheng, Shukla, Anil K., Jacobs, Jon M., Smith, Richard D., Rodland, Karin D., West, G. Alexander, Kohama, Steven G., Glynn, Christine, & Stenzel-Poore, Mary P. Preconditioning in the Rhesus Macaque Induces a Proteomic Signature Following Cerebral Ischemia that Is Associated with Neuroprotection. United States. doi:10.1007/s12975-018-0670-7.
Stevens, Susan L., Liu, Tao, Bahjat, Frances Rena, Petyuk, Vladislav A., Schepmoes, Athena A., Sontag, Ryan L., Gritsenko, Marina A., Wu, Chaochao, Wang, Sheng, Shukla, Anil K., Jacobs, Jon M., Smith, Richard D., Rodland, Karin D., West, G. Alexander, Kohama, Steven G., Glynn, Christine, and Stenzel-Poore, Mary P. Fri . "Preconditioning in the Rhesus Macaque Induces a Proteomic Signature Following Cerebral Ischemia that Is Associated with Neuroprotection". United States. doi:10.1007/s12975-018-0670-7. https://www.osti.gov/servlets/purl/1571272.
@article{osti_1571272,
title = {Preconditioning in the Rhesus Macaque Induces a Proteomic Signature Following Cerebral Ischemia that Is Associated with Neuroprotection},
author = {Stevens, Susan L. and Liu, Tao and Bahjat, Frances Rena and Petyuk, Vladislav A. and Schepmoes, Athena A. and Sontag, Ryan L. and Gritsenko, Marina A. and Wu, Chaochao and Wang, Sheng and Shukla, Anil K. and Jacobs, Jon M. and Smith, Richard D. and Rodland, Karin D. and West, G. Alexander and Kohama, Steven G. and Glynn, Christine and Stenzel-Poore, Mary P.},
abstractNote = {Each year thousands of patients are at risk of cerebral ischemic injury, due to iatrogenic responses to surgical procedures. Prophylactic treatment of these patients as standard care could minimize potential neurological complications. We have shown that protection of brain tissue, in a non-human primate model of cerebral ischemic injury, is possible through pharmacological preconditioning using the immune activator D192935. We postulate that preconditioning with D192935 results in neuroprotective reprogramming that is evident in the brain following experimentally induced cerebral ischemia. We performed quantitative proteomic analysis of cerebral spinal fluid (CSF) collected post-stroke from our previously published efficacy study to determine whether CSF protein profiles correlated with induced protection. Four groups of animals were examined: naïve animals (no treatment or stroke); animals treated with vehicle prior to stroke; D192935 treated and stroked animals, further delineated into two groups, ones that were protected (small infarcts) and those that were not protected (large infarcts). We found that distinct protein clusters defined the protected and non-protected animal groups, with a 16-member cluster of proteins induced exclusively in D192935 protected animals. Seventy percent of the proteins induced in the protected animals have functions that would enhance neuroprotection and tissue repair, including several members associated with M2 macrophages, a macrophage phenotype shown to contribute to neuroprotection and repair during ischemic injury. Overall, these studies highlight the translational importance of CSF biomarkers in defining mechanism and monitoring responses to treatment in development of stroke therapeutics.},
doi = {10.1007/s12975-018-0670-7},
journal = {Translational Stroke Research},
number = 4,
volume = 10,
place = {United States},
year = {2018},
month = {10}
}

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    Works referencing / citing this record:

    Proteomic-Based Approaches for the Study of Ischemic Stroke
    journal, July 2019