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

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.

doi:10.1007/s12975-018-0670-7

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

Journal Article · 18 October 2018 · Translational Stroke Research

DOI: https://doi.org/10.1007/s12975-018-0670-7 · OSTI ID:1571272

Stevens, Susan L. ^[1];

^[2]; Bahjat, Frances Rena ^[1];

^[2]; Schepmoes, Athena A. ^[2]; Sontag, Ryan L. ^[2]; Gritsenko, Marina A. ^[2]; Wu, Chaochao ^[2]; Wang, Sheng ^[2];

^[2]; Jacobs, Jon M. ^[2];

^[2];

^[2]; West, G. Alexander ^[3]; Kohama, Steven G. ^[4]; Glynn, Christine ^[1]; Stenzel-Poore, Mary P. ^[1]

Oregon Health & Science Univ., Portland, OR (United States)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Houston Methodist Neurosurgery, Houston, TX (United States)
Oregon National Primate Research Center, Beaverton, OR (United States)

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.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Laboratory (EMSL)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1571272

Report Number(s):: PNNL-SA-153569; PNWD-SA-10567

Journal Information:: Translational Stroke Research, Journal Name: Translational Stroke Research Journal Issue: 4 Vol. 10; ISSN 1868-4483

Publisher:: Springer Science+Business Media, LLCCopyright Statement

Country of Publication:: United States

Language:: English

References (54)

Stabilin-1/CLEVER-1, a type 2 macrophage marker, is an adhesion and scavenging molecule on human placental macrophages: Innate immunity Palani, Senthil; Maksimow, Mikael; Miiluniemi, Mari European Journal of Immunology, Vol. 41, Issue 7 https://doi.org/10.1002/eji.201041376	journal	June 2011
Neuroprotective actions of endogenous interleukin-1 receptor antagonist (IL-1ra) are mediated by glia Pinteaux, Emmanuel; Rothwell, Nancy J.; Boutin, Herve Glia, Vol. 53, Issue 5 https://doi.org/10.1002/glia.20308	journal	April 2006
Reversed-phase chromatography with multiple fraction concatenation strategy for proteome profiling of human MCF10A cells Wang, Yuexi; Yang, Feng; Gritsenko, Marina A. PROTEOMICS, Vol. 11, Issue 10 https://doi.org/10.1002/pmic.201000722	journal	April 2011
Requirement for distinct vesicle-associated membrane proteins in insulin- and AMP-activated protein kinase (AMPK)-induced translocation of GLUT4 and CD36 in cultured cardiomyocytes Schwenk, R. W.; Dirkx, E.; Coumans, W. A. Diabetologia, Vol. 53, Issue 10 https://doi.org/10.1007/s00125-010-1832-7	journal	June 2010
Systemic and intestinal levels of factor XIII-A: the impact of inflammation on expression in macrophage subtypes Soendergaard, Christoffer; Kvist, Peter Helding; Seidelin, Jakob Benedict Journal of Gastroenterology, Vol. 51, Issue 8 https://doi.org/10.1007/s00535-015-1152-2	journal	December 2015
Preclinical Development of a Prophylactic Neuroprotective Therapy for the Preventive Treatment of Anticipated Ischemia-Reperfusion Injury Bahjat, Frances Rena; Alexander West, G.; Kohama, Steven G. Translational Stroke Research, Vol. 8, Issue 4 https://doi.org/10.1007/s12975-017-0532-8	journal	April 2017
Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial Hausenloy, Derek J.; Mwamure, Peter K.; Venugopal, Vinod The Lancet, Vol. 370, Issue 9587 https://doi.org/10.1016/S0140-6736(07)61296-3	journal	August 2007
Ischemic tolerance and endogenous neuroprotection Dirnagl, Ulrich; Simon, Roger P.; Hallenbeck, John M. Trends in Neurosciences, Vol. 26, Issue 5 https://doi.org/10.1016/S0166-2236(03)00071-7	journal	May 2003
Silent cerebral ischaemia: hidden fingerprints of invasive medical procedures Bendszus, Martin; Stoll, Guido The Lancet Neurology, Vol. 5, Issue 4 https://doi.org/10.1016/S1474-4422(06)70412-4	journal	April 2006
New ischaemic brain lesions on MRI after stenting or endarterectomy for symptomatic carotid stenosis: a substudy of the International Carotid Stenting Study (ICSS) Bonati, Leo H.; Jongen, Lisa M.; Haller, Sven The Lancet Neurology, Vol. 9, Issue 4 https://doi.org/10.1016/S1474-4422(10)70057-0	journal	April 2010
Down regulation of GALNT3 contributes to endothelial cell injury via activation of p38 MAPK signaling pathway Guo, Liwei; Wang, Laiyuan; Li, Hongfan Atherosclerosis, Vol. 245 https://doi.org/10.1016/j.atherosclerosis.2015.12.019	journal	February 2016
Regulation of glucose and lipid homeostasis by adiponectin: Effects on hepatocytes, pancreatic β cells and adipocytes Tao, Caroline; Sifuentes, Angelica; Holland, William L. Best Practice & Research Clinical Endocrinology & Metabolism, Vol. 28, Issue 1 https://doi.org/10.1016/j.beem.2013.11.003	journal	January 2014
Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer Zhang, Hui; Liu, Tao; Zhang, Zhen Cell, Vol. 166, Issue 3 https://doi.org/10.1016/j.cell.2016.05.069	journal	July 2016
MASIC: A software program for fast quantitation and flexible visualization of chromatographic profiles from detected LC–MS(/MS) features Monroe, Matthew E.; Shaw, Jason L.; Daly, Don S. Computational Biology and Chemistry, Vol. 32, Issue 3 https://doi.org/10.1016/j.compbiolchem.2008.02.006	journal	June 2008
Azithromycin protects mice against ischemic stroke injury by promoting macrophage transition towards M2 phenotype Amantea, Diana; Certo, Michelangelo; Petrelli, Francesco Experimental Neurology, Vol. 275 https://doi.org/10.1016/j.expneurol.2015.10.012	journal	January 2016
Silent Brain Injury After Cardiac Surgery: A Review Sun, Xiumei; Lindsay, Joseph; Monsein, Lee H. Journal of the American College of Cardiology, Vol. 60, Issue 9 https://doi.org/10.1016/j.jacc.2012.02.079	journal	August 2012
New asymptomatic ischemic lesions on diffusion-weighted imaging after cerebral angiography Shibazaki, Kensaku; Iguchi, Yasuyuki; Kimura, Kazumi Journal of the Neurological Sciences, Vol. 266, Issue 1-2 https://doi.org/10.1016/j.jns.2007.09.017	journal	March 2008
Remote organ ischemic preconditioning protect brain from ischemic damage following asphyxial cardiac arrest Dave, Kunjan R.; Saul, Isabel; Prado, Ricardo Neuroscience Letters, Vol. 404, Issue 1-2 https://doi.org/10.1016/j.neulet.2006.05.037	journal	August 2006
Globular adiponectin elicits neuroprotection by inhibiting NADPH oxidase-mediated oxidative damage in ischemic stroke Song, W.; Huo, T.; Guo, F. Neuroscience, Vol. 248 https://doi.org/10.1016/j.neuroscience.2013.05.063	journal	September 2013
Tandem Mass Tags: A Novel Quantification Strategy for Comparative Analysis of Complex Protein Mixtures by MS/MS Thompson, Andrew; Schäfer, Jürgen; Kuhn, Karsten Analytical Chemistry, Vol. 75, Issue 8 https://doi.org/10.1021/ac0262560	journal	April 2003
Poly-IC Preconditioning Protects against Cerebral and Renal Ischemia-Reperfusion Injury Packard, Amy E. B.; Hedges, Jason C.; Bahjat, Frances R. Journal of Cerebral Blood Flow & Metabolism, Vol. 32, Issue 2 https://doi.org/10.1038/jcbfm.2011.160	journal	November 2011
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. Journal of Cerebral Blood Flow & Metabolism, Vol. 31, Issue 5 https://doi.org/10.1038/jcbfm.2011.6	journal	December 2010
Proteogenomics connects somatic mutations to signalling in breast cancer Mertins, Philipp; Mani, D. R.; Ruggles, Kelly V. Nature, Vol. 534, Issue 7605 https://doi.org/10.1038/nature18003	journal	May 2016
MS-GF+ makes progress towards a universal database search tool for proteomics Kim, Sangtae; Pevzner, Pavel A. Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms6277	journal	October 2014
Blocking CLEC14A-MMRN2 binding inhibits sprouting angiogenesis and tumour growth Noy, P. J.; Lodhia, P.; Khan, K. Oncogene, Vol. 34, Issue 47 https://doi.org/10.1038/onc.2015.34	journal	March 2015
Toll-Like Receptor 9: A New Target of Ischemic Preconditioning in the Brain Stevens, Susan L.; Ciesielski, Thomas MP; Marsh, Brenda J. Journal of Cerebral Blood Flow & Metabolism, Vol. 28, Issue 5 https://doi.org/10.1038/sj.jcbfm.9600606	journal	January 2008
A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery Meybohm, Patrick; Bein, Berthold; Brosteanu, Oana New England Journal of Medicine, Vol. 373, Issue 15 https://doi.org/10.1056/NEJMoa1413579	journal	October 2015
Statistical significance for genomewide studies Storey, J. D.; Tibshirani, R. Proceedings of the National Academy of Sciences, Vol. 100, Issue 16, p. 9440-9445 https://doi.org/10.1073/pnas.1530509100	journal	July 2003
Endotoxin pretreatment increases endogenous myocardial catalase activity and decreases ischemia-reperfusion injury of isolated rat hearts. Brown, J. M.; Grosso, M. A.; Terada, L. S. Proceedings of the National Academy of Sciences, Vol. 86, Issue 7 https://doi.org/10.1073/pnas.86.7.2516	journal	April 1989
α ₁ -Acid Glycoprotein Up-regulates CD163 via TLR4/CD14 Protein Pathway : POSSIBLE PROTECTION AGAINST HEMOLYSIS-INDUCED OXIDATIVE STRESS Komori, Hisakazu; Watanabe, Hiroshi; Shuto, Tsuyoshi Journal of Biological Chemistry, Vol. 287, Issue 36 https://doi.org/10.1074/jbc.M112.353771	journal	July 2012
Type I Interferon-mediated Stimulation of T Cells by CpG DNA Sun, Siquan; Zhang, Xiaohong; Tough, David F. The Journal of Experimental Medicine, Vol. 188, Issue 12 https://doi.org/10.1084/jem.188.12.2335	journal	December 1998
C1q and Mannose Binding Lectin Engagement of Cell Surface Calreticulin and Cd91 Initiates Macropinocytosis and Uptake of Apoptotic Cells Ogden, Carol Anne; deCathelineau, Aimee; Hoffmann, Peter R. The Journal of Experimental Medicine, Vol. 194, Issue 6 https://doi.org/10.1084/jem.194.6.781	journal	September 2001
InParanoid 8: orthology analysis between 273 proteomes, mostly eukaryotic Sonnhammer, Erik L. L.; Östlund, Gabriel Nucleic Acids Research, Vol. 43, Issue D1 https://doi.org/10.1093/nar/gku1203	journal	November 2014
limma powers differential expression analyses for RNA-sequencing and microarray studies Ritchie, Matthew E.; Phipson, Belinda; Wu, Di Nucleic Acids Research, Vol. 43, Issue 7 https://doi.org/10.1093/nar/gkv007	journal	January 2015
Heterogeneity in the Human Response to Immunostimulatory CpG Oligodeoxynucleotides Leifer, Cynthia A.; Verthelyi, Daniela; Klinman, Dennis M. Journal of Immunotherapy, Vol. 26, Issue 4 https://doi.org/10.1097/00002371-200307000-00003	journal	January 2003
In vivo over-expression of interleukin-10 increases resistance to focal brain ischemia in mice de Bilbao, Fabienne; Arsenijevic, Denis; Moll, Thomas Journal of Neurochemistry, Vol. 110, Issue 1 https://doi.org/10.1111/j.1471-4159.2009.06098.x	journal	July 2009
Cerebrospinal fluid biomarkers as a measure of disease activity and treatment efficacy in relapsing-remitting multiple sclerosis Novakova, Lenka; Axelsson, Markus; Khademi, Mohsen Journal of Neurochemistry, Vol. 141, Issue 2 https://doi.org/10.1111/jnc.13881	journal	November 2016
Procarboxypeptidase U (proCPU, TAFI, proCPB2) in cerebrospinal fluid during ischemic stroke is associated with stroke progression, outcome and blood-brain barrier dysfunction Mertens, J. C.; Leenaerts, D.; Brouns, R. Journal of Thrombosis and Haemostasis, Vol. 16, Issue 2 https://doi.org/10.1111/jth.13914	journal	December 2017
Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages Lovren, Fina; Pan, Yi; Quan, Adrian American Journal of Physiology-Heart and Circulatory Physiology, Vol. 299, Issue 3 https://doi.org/10.1152/ajpheart.00115.2010	journal	September 2010
The role of lysyl oxidase family members in the stabilization of abdominal aortic aneurysms Remus, Ebony Washington; O'Donnell, Robert E.; Rafferty, Kathryn American Journal of Physiology-Heart and Circulatory Physiology, Vol. 303, Issue 8 https://doi.org/10.1152/ajpheart.00217.2012	journal	October 2012
Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms Rőszer, Tamás Mediators of Inflammation, Vol. 2015 https://doi.org/10.1155/2015/816460	journal	January 2015
Adiponectin Prevents Cerebral Ischemic Injury Through Endothelial Nitric Oxide Synthase–Dependent Mechanisms Nishimura, Masaki; Izumiya, Yasuhiro; Higuchi, Akiko Circulation, Vol. 117, Issue 2 https://doi.org/10.1161/CIRCULATIONAHA.107.725044	journal	January 2008
Cerebral Embolization During Transcatheter Aortic Valve Implantation: A Transcranial Doppler Study Kahlert, Philipp; Al-Rashid, Fadi; Döttger, Philipp Circulation, Vol. 126, Issue 10 https://doi.org/10.1161/CIRCULATIONAHA.112.092544	journal	September 2012
Temporal analysis of blood–brain barrier disruption and cerebrospinal fluid matrix metalloproteinases in rhesus monkeys subjected to transient ischemic stroke Zhang, Yingqian; Fan, Feng; Zeng, Guojun Journal of Cerebral Blood Flow & Metabolism, Vol. 37, Issue 8 https://doi.org/10.1177/0271678X16680221	journal	January 2016
Molecular association of pathogenetic contributors to pre-eclampsia (pre-eclampsia associome) Glotov, Andrey S.; Tiys, Evgeny S.; Vashukova, Elena S. BMC Systems Biology, Vol. 9, Issue Suppl 2 https://doi.org/10.1186/1752-0509-9-S2-S4	journal	January 2015
C1q and MBL, components of the innate immune system, influence monocyte cytokine expression Fraser, D. A.; Bohlson, S. S.; Jasinskiene, N. Journal of Leukocyte Biology, Vol. 80, Issue 1 https://doi.org/10.1189/jlb.1105683	journal	May 2006
Adiponectin Upregulates SHBG Production: Molecular Mechanisms and Potential Implications Simó, Rafael; Saez-Lopez, Cristina; Lecube, Albert Endocrinology, Vol. 155, Issue 8 https://doi.org/10.1210/en.2014-1072	journal	August 2014
Multiple Preconditioning Paradigms Converge on Interferon Regulatory Factor-Dependent Signaling to Promote Tolerance to Ischemic Brain Injury Stevens, S. L.; Leung, P. Y.; Vartanian, K. B. Journal of Neuroscience, Vol. 31, Issue 23 https://doi.org/10.1523/JNEUROSCI.0821-11.2011	journal	June 2011
Heparan Sulfate Sugar Modifications Mediate the Functions of Slits and Other Factors Needed for Mouse Forebrain Commissure Development Conway, C. D.; Howe, K. M.; Nettleton, N. K. Journal of Neuroscience, Vol. 31, Issue 6 https://doi.org/10.1523/JNEUROSCI.2579-10.2011	journal	February 2011
Microglia and Monocytes/Macrophages Polarization Reveal Novel Therapeutic Mechanism against Stroke Kanazawa, Masato; Ninomiya, Itaru; Hatakeyama, Masahiro International Journal of Molecular Sciences, Vol. 18, Issue 10 https://doi.org/10.3390/ijms18102135	journal	October 2017
Safety and Therapeutic Potential of M2 Macrophages in Stroke Treatment Chernykh, Elena R.; Shevela, Ekaterina Ya.; Starostina, Nataliya M. Cell Transplantation, Vol. 25, Issue 8 https://doi.org/10.3727/096368915X690279	journal	August 2016
Delineation of a CpG Phosphorothioate Oligodeoxynucleotide for Activating Primate Immune Responses In Vitro and In Vivo Hartmann, Gunther; Weeratna, Risini D.; Ballas, Zuhair K. The Journal of Immunology, Vol. 164, Issue 3 https://doi.org/10.4049/jimmunol.164.3.1617	journal	February 2000
Oligodeoxynucleotides Containing CpG Motifs Induce Low Levels of TNF-α in Human B Lymphocytes: Possible Adjuvants for Th1 Responses Bohle, Barbara; Orel, Lukas; Kraft, Dietrich The Journal of Immunology, Vol. 166, Issue 6 https://doi.org/10.4049/jimmunol.166.6.3743	journal	March 2001
Novel Function of Alternatively Activated Macrophages: Stabilin-1-Mediated Clearance of SPARC Kzhyshkowska, Julia; Workman, Gail; Cardó-Vila, Marina The Journal of Immunology, Vol. 176, Issue 10 https://doi.org/10.4049/jimmunol.176.10.5825	journal	May 2006

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60 APPLIED LIFE SCIENCES
cerebral spinal fluid
neuroprotection
non-human primates
proteomics
stroke

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

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Cited By (2)

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