Innate and adaptive immune response in stroke: Focus on epigenetic regulation

Journal of Neuroimmunology

Volumn 289, Issue , 2015, Pages 111-120

  Picascia, Antonietta ^a   Grimaldi, Vincenzo ^a   Iannone, Carmela ^a   Soricelli, Andrea ^b,c   Napoli, Claudio ^a,b  

^a SECOND UNIVERSITY OF NAPLES   (Italy)

^b IRCCS SDN   (Italy)

^c UNIVERSITY OF NAPLES PARTHENOPE   (Italy)

Author keywords

Antagomir; Epigenetics; HDACi; Innate and adaptive response; Stroke

Indexed keywords

COLLAGENASE 3; GELATINASE A; GELATINASE B; HIGH MOBILITY GROUP B1 PROTEIN; INTERLEUKIN 10; MICRORNA; MICRORNA 126; MICRORNA 146; MICRORNA 155; MICRORNA 29C; MICRORNA 30A; STROMELYSIN; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; TRANSCRIPTION FACTOR FOXP3; UNCLASSIFIED DRUG;

ADAPTIVE IMMUNITY; BRAIN ISCHEMIA; DENDRITIC CELL; DNA METHYLATION; EPIGENETICS; HISTONE MODIFICATION; HUMAN; INNATE IMMUNITY; MACROPHAGE; MICROGLIA; NEUTROPHIL; NONHUMAN; PRIORITY JOURNAL; PROTEIN METHYLATION; REGULATORY T LYMPHOCYTE; REVIEW; T LYMPHOCYTE ACTIVATION; CEREBROVASCULAR ACCIDENT; GENETIC EPIGENESIS; GENETICS; IMMUNOLOGY; PATHOPHYSIOLOGY;

ADAPTIVE IMMUNITY; EPIGENESIS, GENETIC; HUMANS; IMMUNITY, INNATE; STROKE;

EID: 84947933321     PISSN: 01655728     EISSN: 18728421     Source Type: Journal    
DOI: 10.1016/j.jneuroim.2015.10.013     Document Type: Review

References (122)

1. Alam M.M., O'Neill L.A. MicroRNAs and the resolution phase of inflammation in macrophages. Eur. J. Immunol. 2011, 41:2482-2485.
2. An C., Shi Y., Li P., Hu X., Gan Y., Stetler R.A., Leak R.K., Gao Y., Sun B.L., Zheng P., Chen J. Molecular dialogs between the ischemic brain and the peripheral immune system: dualistic roles in injury and repair. Prog. Neurobiol. 2014, 115:6-24.
3. Baccarelli A., Wright R., Bollati V., Litonjua A., Zanobetti A., Tarantini L., Sparrow D., Vokonas P., Schwartz J. Ischemic heart disease and stroke in relation to blood DNA methylation. Epidemiology 2010, 21:819-828.
4. Bai Y., Zhu Z., Gao Z., Kong Y. TLR2 signaling directs NO-dependent MMP-9 induction in mouse microglia. Neurosci. Lett. 2014, 571:5-10.
5. Baker A.H., Sica V., Work L.M., Williams-Ignarro S., de Nigris F., Lerman L.O., Casamassimi A., Lanza A., Schiano C., Rienzo M., Ignarro L.J., Napoli C. Brain protection using autologous bone marrow cell, metalloproteinase inhibitors, and metabolic treatment in cerebral ischemia. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:3597-3602.
6. Bazzoni F., Rossato M., Fabbri M., Gaudiosi D., Mirolo M., Mori L., Tamassia N., Mantovani A., Cassatella M.A., Locati M. Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signals. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:5282-5287.
7. Beier U.H., Wang L., Han R., Akimova T., Liu Y., Hancock W.W. Histone deacetylases 6 and 9 and sirtuin-1 control Foxp3+ regulatory T cell function through shared and isoform-specific mechanisms. Sci. Signal. 2012, 5:ra45.
8. Brea D., Agulla J., Rodríguez-Yáñez M., Barral D., Ramos-Cabrer P., Campos F., Almeida A., Dávalos A., Castillo J. Regulatory T cells modulate inflammation and reduce infarct volume in experimental brain ischaemia. J. Cell. Mol. Med. 2014, 18:1571-1579.
9. Brown P.N., Yin H. PNA-based microRNA inhibitors elicit anti-inflammatory effects in microglia cells. Chem. Commun. (Camb.) 2013, 49:4415-4417.
10. Caird J., Napoli C., Taggart C., Farrell M., Bouchier-Hayes D. Matrix metalloproteinases 2 and 9 in human atherosclerotic and non-atherosclerotic cerebral aneurysms. Eur. J. Neurol. 2006, 13:1098-1105.
11. Caso J.R., Pradillo J.M., Hurtado O., Lorenzo P., Moro M.A., Lizasoain I. Toll-like receptor 4 is involved in brain damage and inflammation after experimental stroke. Circulation 2007, 115:1599-1608.
12. Chamorro Á., Meisel A., Planas A.M., Urra X., van de Beek D., Veltkamp R. The immunology of acute stroke. Nat. Rev. Neurol. 2012, 8:401-410.
13. Chaturvedi M., Kaczmarek L. Mmp-9 inhibition: a therapeutic strategy in ischemic stroke. Mol. Neurobiol. 2014, 49:563-573.
14. Chiba T., Umegaki K. Pivotal roles of monocytes/macrophages in stroke. Mediat. Inflamm. 2013, 2013:759103.
15. Curtale G., Mirolo M., Renzi T.A., Rossato M., Bazzoni F., Locati M. Negative regulation of Toll-like receptor 4 signaling by IL-10-dependent microRNA-146b. Proc. Natl. Acad. Sci. U. S. A. 2013, 110:11499-11504.
16. D'Armiento F.P., Bianchi A., de Nigris F., Capuzzi D.M., D'Armiento M.R., Crimi G., Abete P., Palinski W., Condorelli M., Napoli C. Age-related effects on atherogenesis and scavenger enzymes of intracranial and extracranial arteries in men without classic risk factors for atherosclerosis. Stroke 2001, 32:2472-2479.
17. del Zoppo G.J. The neurovascular unit, matrix proteases, and innate inflammation. Ann. N. Y. Acad. Sci. 2010, 1207:46-49.
18. Dinarello C.A. Anti-inflammatory agents: present and future. Cell 2010, 140:935-950.
19. Dregan A., Charlton J., Wolfe C.D., Gulliford M.C., Markus H.S. Is sodium valproate, an HDAC inhibitor, associated with reduced risk of stroke and myocardial infarction? A nested case-control study. Pharmacoepidemiol. Drug Saf. 2014, 23:759-767.
20. Famakin B.M., Mou Y., Johnsonm K., Spatz M., Hallenbeck J. A new role for downstream Toll-like receptor signaling in mediating immediate early gene expression during focal cerebral ischemia. J. Cereb. Blood Flow Metab. 2014, 34:258-267.
21. Faraco G., Pancani T., Formentini L., Mascagni P., Fossati G., Leoni F., Moroni F., Chiarugi A. Pharmacological inhibition of histone deacetylases by suberoylanilide hydroxamic acid specifically alters gene expression and reduces ischemic injury in the mouse brain. Mol. Pharmacol. 2006, 70:1876-1884.
22. Gesuete R., Kohama S.G., Stenzel-Poore M.P. Toll-like receptors and ischemic brain injury. J. Neuropathol. Exp. Neurol. 2014, 73:378-386.
23. Gidday J.M., Gasche Y.G., Copin J.C., Shah A.R., Perez R.S., Shapiro S.D., Chan P.H., Park T.S. Leukocyte-derived matrix metalloproteinase-9 mediates blood-brain barrier breakdown and is proinflammatory after transient focal cerebral ischemia. Am. J. Physiol. Heart Circ. Physiol. 2005, 289:H558-H568.
24. Graham C.A., Chan R.W., Chan D.Y., Chan C.P., Wong L.K., Rainer T.H. Matrix metalloproteinase 9 mRNA: an early prognostic marker for patients with acute stroke. Clin. Biochem. 2012, 45:352-355.
25. Grau A.J., Urbanek C., Palm F. Common infections and the risk of stroke. Nat. Rev. Neurol. 2010, 6:681-694.
26. Greco S., De Simone M., Colussi C., Zaccagnini G., Fasanaro P., Pescatori M., Cardani R., Perbellini R., Isaia E., Sale P., Meola G., Capogrossi M.C., Gaetano C., Martelli F. Common micro-RNA signature in skeletal muscle damage and regeneration induced by Duchenne muscular dystrophy and acute ischemia. FASEB J. 2009, 23:3335-3346.
27. Grimaldi V., Vietri M.T., Schiano C., Picascia A., De Pascale M.R., Fiorito C., Casamassimi A., Napoli C. Epigenetic reprogramming in atherosclerosis. Curr. Atheroscler. Rep. 2015, 17:476.
28. Hajat C., Heuschmann P.U., Coshall C., Padayachee S., Chambers J., Rudd A.G., Wolfe C.D. Incidence of aetiological subtypes of stroke in a multi-ethnic population based study: the South London Stroke Register. J. Neurol. Neurosurg. Psychiatry 2011, 82:527-533.
29. Harari O.A., Liao J.K. NF-κB and innate immunity in ischemic stroke. Ann. N. Y. Acad. Sci. 2010, 1207:32-40.
30. Hayakawa K., Qiu J., Lo E.H. Biphasic actions of HMGB1 signaling in inflammation and recovery after stroke. Ann. N. Y. Acad. Sci. 2010, 1207:50-57.
31. He M., Zhang B., Wei X., Wang Z., Fan B., Du P., Zhang Y., Jian W., Chen L., Wang L., Fang H., Li X., Wang P.A., Yi F. HDAC4/5-HMGB1 signalling mediated by NADPH oxidase activity contributes to cerebral ischaemia/reperfusion injury. J. Cell. Mol. Med. 2013, 17:531-542.
32. He X., Jing Z., Cheng G. MicroRNAs: new regulators of Toll-like receptor signalling pathways. Biomed. Res. Int. 2014, 2014:945169.
33. Hua F., Ma J., Ha T., Kelley J.L., Kao R.L., Schweitzer J.B., Kalbfleisch J.H., Williams D.L., Li C. Differential roles of TLR2 and TLR4 in acute focal cerebral ischemia/reperfusion injury in mice. Brain Res. 2009, 1262:100-108.
34. Huang J., Xie Y., Sun X., Zeh H.J., Kang R., Lotze M.T., Tang D. DAMPs, ageing, and cancer: the 'DAMP Hypothesis'. Ageing Res. Rev. 2014.
35. Hug A., Liesz A., Muerle B., Zhou W., Ehrenheim J., Lorenz A., Dalpke A., Veltkamp R. Reduced efficacy of circulating costimulatory cells after focal cerebral ischemia. Stroke 2011, 42:3580-3586.
36. Jickling G.C., Anderm B.P., Zhan X., Noblett D., Stamova B., Liu D. microRNA expression in peripheral blood cells following acute ischemic stroke and their predicted gene targets. PLoS One 2014, 9:e99283.
37. Jickling G.C., Zhan X., Stamova B., Ander B.P., Tian Y., Liu D., Sison S.M., Verro P., Johnston S.C., Sharp F.R. Ischemic transient neurological events identified by immune response to cerebral ischemia. Stroke 2012, 43:1006-1012.
38. Kalani A., Kamat P.K., Familtseva A., Chaturvedi P., Muradashvili N., Narayanan N., Tyagi S.C., Tyagi N. Role of microRNA29b in blood-brain barrier dysfunction during hyperhomocysteinemia: an epigenetic mechanism. J. Cereb. Blood Flow Metab. 2014, 34:1212-1222.
39. Kalin J.H., Zhang H., Gaudrel-Grosay S., Vistoli G., Kozikowski A.P. Chiral mercaptoacetamides display enantioselective inhibition of histone deacetylase6 and exhibit neuroprotection in cortical neuron models of oxidative stress. ChemMedChem 2012, 7:425-439.
40. Kamel H., Iadecola C. Brain-immune interactions and ischemic stroke: clinical implications. Arch. Neurol. 2012, 69:576-581.
41. Kannan V., Brouwer N., Hanisch U.K., Regen T., Eggen B.J., Boddeke H.W. Histone deacetylase inhibitors suppress immune activation in primary mouse microglia. J. Neurosci. Res. 2013, 91:1133-1142.
42. Keep R.F., Zhou N., Xiang J., Andjelkovic A.V., Hua Y., Xi G. Vascular disruption and blood-brain barrier dysfunction in intracerebral hemorrhage. Fluids Barriers CNS 2014, 11:18.
43. Kim H.J., Chuang D.M. HDAC inhibitors mitigate ischemia-induced oligodendrocyte damage: potential roles of oligodendrogenesis, VEGF, and anti-inflammation. Am. J. Transl. Res. 2014, 6:206-223.
44. Kim H.J., Rowe M., Ren M., Hong J.S., Chen P.S., Chuang D.M. Histone deacetylase inhibitors exhibit anti-inflammatory and neuroprotective effects in a rat permanent ischemic model of stroke: multiple mechanisms of action. J. Pharmacol. Exp. Ther. 2007, 321:892-901.
45. Kim J., Song T.J., Park J.H., Lee H.S., Nam C.M., Nam H.S., Kim Y.D., Heo J.H. Different prognostic value of white blood cell subtypes in patients with acute cerebral infarction. Atherosclerosis 2012, 222:464-467.
46. Kleinschnitz C., Kraft P., Dreykluft A., Hagedorn I., Göbel K., Schuhmann M.K., Langhauser F., Helluy X., Schwarz T., Bittner S., Mayer C.T., Brede M., Varallyay C., Pham M., Bendszus M., Jakob P., Magnus T., Meuth S.G., Iwakura Y., Zernecke A., Sparwasser T., Nieswandt B., Stoll G., Wiendl H. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature. Blood 2013, 121:679-691.
47. Kohlhaas S., Garden O.A., Scudamore C., Turner M., Okkenhaug K., Vigorito E. Cutting edge: the Foxp3 target miR-155 contributes to the development of regulatory T cells. J. Immunol. 2009, 182:2578-2582.
48. Kong H., Omran A., Ashhab M.U., Gan N., Peng J., He F., Wu L., Deng X., Yin F. Changes in microglial inflammation-related and brain-enriched microRNAs expressions in response to in vitro oxygen-glucose deprivation. Neurochem. Res. 2014, 39:233-243.
49. Lakshmaiah K.C., Jacob L.A., Aparna S., Lokanatha D., Saldanha S.C. Epigenetic therapy of cancer with histone deacetylase inhibitors. J. Cancer Res. Ther. 2014, 10:469-478.
50. Laloux P. Risk and benefit of statins in stroke secondary prevention. Curr. Vasc. Pharmacol. 2013, 11:812-816.
51. Langley B., D'Annibale M.A., Suh K., Ayoub I., Tolhurst A., Bastan B., Yang L., Ko B., Fisher M., Cho S., Beal M.F., Ratan R.R. Pulse inhibition of histone deacetylases induces complete resistance to oxidative death in cortical neurons without toxicity and reveals a role for cytoplasmic p21(waf1/cip1) in cell cycle-independent neuroprotection. J. Neurosci. 2008, 28:163-176.
52. Lanzillotta A., Pignataro G., Branca C., Cuomo O., Sarnico I., Benarese M., Annunziato L., Spano P., Pizzi M. Targeted acetylation of NF kappaB/RelA and histones by epigenetic drugs reduces post-ischemic brain injury in mice with an extended therapeutic window. Neurobiol. Dis. 2013, 49:177-189.
53. Lehnardt S., Lehmann S., Kaul D., Tschimmel K., Hoffmann O., Cho S., Krueger C., Nitsch R., Meisel A., Weber J.R. Toll-like receptor 2 mediates CNS injury in focal cerebral ischemia. J. Neuroimmunol. 2007, 190:28-33.
54. Li P., Gan Y., Sun B.L., Zhang F., Lu B., Gao Y., Liang W., Thomson A.W., Chen J., Hu X. Adoptive regulatory T-cell therapy protects against cerebral ischemia. Ann. Neurol. 2013, 74:458-471.
55. Liesz A., Suri-Payer E., Veltkamp C., Doerr H., Sommer C., Rivest S., Giese T., Veltkamp R. Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat. Med. 2009, 15:192-199.
56. Liesz A., Zhou W., Na S.Y., Hämmerling G.J., Garbi N., Karcher S., Mracsko E., Backs J., Rivest S., Veltkamp R. Boosting regulatory T cells limits neuroinflammation in permanent cortical stroke. Neuroscience 2013, 33:17350-17362.
57. Lindsberg P.J., Strbian D., Karjalainen-Lindsberg M.L. Mast cells as early responders in the regulation of acute blood-brain barrier changes after cerebral ischemia and hemorrhage. J. Cereb. Blood Flow Metab. 2010, 30:689-702.
58. Liu Y., Lai L., Chen Q., Song Y., Xu S., Ma F., Wang X., Wang J., Yu H., Cao X., Wang Q. MicroRNA-494 is required for the accumulation and functions of tumor-expanded myeloid-derived suppressor cells via targeting of PTEN. J. Immunol. 2012, 188:5500-5510.
59. Liu Y., Zhang J., Han R., Liu H., Sun D., Liu X. Downregulation of serum brain specific microRNA is associated with inflammation and infarct volume in acute ischemic stroke. J. Clin. Neurosci. 2015, 22:291-295.
60. Long G., Wang F., Li H., Yin Z., Sandip C., Lou Y., Wang Y., Chen C., Wang D.W. Circulating miR-30a, miR-126 and let-7b as biomarker for ischemic stroke in humans. BMC Neurol. 2013, 13:178.
61. Lu L.F., Liston A. MicroRNA in the immune system, microRNA as an immune system. Immunology 2009, 127:291-298.
62. Lu L.F., Boldin M.P., Chaudhry A., Lin L.L., Taganov K.D., Hanada T., Yoshimura A., Baltimore D., Rudensky A.Y. Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses. Cell 2010, 142:914-929.
63. Lu L.F., Thai T.H., Calado D.P., Chaudhry A., Kubo M., Tanaka K., Loeb G.B., Lee H., Yoshimura A., Rajewsky K., Rudensky A.Y. Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity 2009, 30:80-91.
64. Miao Z., He Y., Xin N., Sun M., Chen L., Lin L., Li J., Kong J., Jin P., Xu X. Altering 5-hydroxymethylcytosine modification impacts ischemic brain injury. Hum. Mol. Genet. 2015, 24:5855-5866.
65. Moon J.M., Xu L., Giffard R.G. Inhibition of microRNA-181 reduces forebrain ischemia-induced neuronal loss. J. Cereb. Blood Flow Metab. 2013, 33:1976-1982.
66. Murphy S.P., Lee R.J., McClean M.E., Pemberton H.E., Uo T., Morrison R.S., Bastian C., Baltan S. MS-275, a class I histone deacetylase inhibitor, protects the p53-deficient mouse against ischemic injury. J. Neurochem. 2014, 129:509-515.
67. Murray P.J. Understanding and exploiting the endogenous interleukin-10/STAT3-mediated anti-inflammatory response. Curr. Opin. Pharmacol. 2006, 6:379-386.
68. Na S.Y., Mracsko E., Liesz A., Hünig T., Veltkamp R. Amplification of regulatory T cells using a CD28 superagonist reduces brain damage after ischemic stroke in mice. Stroke 2015, 46:212-220.
69. Nace G., Evankovich J., Eid R., Tsung A. Dendritic cells and damage-associated molecular patterns: endogenous danger signals linking innate and adaptive immunity. J. Innate Immun. 2012, 4:6-15.
70. Nahid M.A., Yao B., Dominguez-Gutierrez P.R., Kesavalu L., Satoh M., Chan E.K. Regulation of TLR2-mediated tolerance and cross-tolerance through IRAK4 modulation by miR-132 and miR-212. J. Immunol. 2013, 190:1250-1263.
71. Napoli C. MMP inhibition and the development of cerebrovascular atherosclerosis: the road ahead. Stroke 2002, 33:2864-2865.
72. Napoli C. Developmental mechanisms involved in the primary prevention of atherosclerosis and cardiovascular disease. Curr. Atheroscler. Rep. 2011, 13:170-175.
73. Napoli C., Salomone S., Godfraind T., Palinski W., Capuzzi D.M., Palumbo G., D'Armiento F.P., Donzelli R., de Nigris F., Capizzi R.L., Mancini M., Gonnella J.S., Bianchi A. 1,4-Dihydropyridine calcium channel blockers inhibit plasma and LDL oxidation and formation of oxidation-specific epitopes in the arterial wall and prolong survival in stroke-prone spontaneously hypertensive rats. Stroke 1999, 30:1907-1915.
74. Napoli C., Witztum J.L., de Nigris F., Palumbo G., D'Armiento F.P., Palinski W. Intracranial arteries of human fetuses are more resistant to hypercholesterolemia-induced fatty streak formation than extracranial arteries. Circulation 1999, 99:2003-2010.
75. Offner H., Subramanian S., Parker S.M., Wang C., Afentoulis M.E., Lewis A., Vandenbark A.A., Hurn P.D. Splenic atrophy in experimental stroke is accompanied by increased regulatory T cells and circulating macrophages. J. Immunol. 2006, 176:6523-6531.
76. Offner H., Vandenbark A.A., Hurn P.D. Effect of experimental stroke on peripheral immunity: CNS ischemia induces profound immunosuppression. Neuroscience 2009, 158:1098-1111.
77. Olivieri F., Rippo M.R., Prattichizzo F., Babini L., Graciotti L., Recchioni R., Procopio A.D. Toll like receptor signaling in "inflammaging": microRNA as new players. Immun. Ageing 2013, 10:11.
78. O'Neill L.A., Sheedy F.J., McCoy C.E. MicroRNAs: the fine-tuners of Toll-like receptor signalling. Nat. Rev. Immunol. 2011, 11:163-175.
79. Ouyang Y.B., Lu Y., Yue S., Xu L.J., Xiong X.X., White R.E., Sun X., Giffard R.G. miR-181 regulates GRP78 and influences outcome from cerebral ischemia in vitro and in vivo. Neurobiol. Dis. 2012, 45:555-563.
80. Pandi G., Nakka V.P., Dharap A., Roopra A., Vemuganti R. MicroRNA miR-29c down-regulation leading to de-repression of its target DNA methyltransferase 3a promotes ischemic brain damage. PLoS ONE 2013, 8.
81. Peng G., Yuan Y., Wu S., He F., Hu Y., Luo B. MicroRNA let-7e is a potential circulating biomarker of acute stage ischemic stroke. Transl. Stroke Res. 2015, 10.1007/s12975-015-0422-x.
82. Peng Z., Li J., Li Y., Yang X., Feng S., Han S., Li J. Downregulation of miR-181b in mouse brain following ischemic stroke induces neuroprotection against ischemic injury through targeting heat shock protein A5 and ubiquitin carboxyl-terminal hydrolase isozyme L1. J. Neurosci. Res. 2013, 91:1349-1362.
83. Perez-de-Puig I., Miró-Mur F., Ferrer-Ferrer M., Gelpi E., Pedragosa J., Justicia C., Urra X., Chamorro A., Planas A.M. Neutrophil recruitment to the brain in mouse and human ischemic stroke. Acta Neuropathol. 2014, 129:239-257.
84. Philippe L., Alsaleh G., Suffert G., Meyer A., Georgel P., Sibilia J., Wachsmann D., Pfeffer S. TLR2 expression is regulated by microRNA miR-19 in rheumatoid fibroblast-like synoviocytes. J. Immunol. 2012, 188:454-461.
85. Picascia A., Grimaldi V., Pignalosa O., De Pascale M.R., Schiano C., Napoli C. Epigenetic control of autoimmune diseases: from bench to bedside. Clin. Immunol. 2015, 157:1-15.
86. Pons D., de Vries F.R., van den Elsen P.J., Heijmans B.T., Quax P.H., Jukema J.W. Epigenetic histone acetylation modifiers in vascular remodelling: new targets for therapy in cardiovascular disease. Eur. Heart J. 2009, 30:266-277.
87. Price C.J., Menon D.K., Peters A.M., Ballinger J.R., Barber R.W., Balan K.K., Lynch A., Xuereb J.H., Fryer T., Guadagno J.V., Warburton E.A. Cerebral neutrophil recruitment, histology, and outcome in acute ischemic stroke: an imaging-based study. Stroke 2004, 35:1659-1664.
88. Ren M., Leng Y., Jeong M., Leeds P.R., Chuang D.M. Valproic acid reduces brain damage induced by transient focal cerebral ischemia in rats: potential roles of histone deacetylase inhibition and heat shock protein induction. J. Neurochem. 2004, 89:1358-1367.
89. Ren X., Akiyoshi K., Vandenbark A.A., Hurn P.D., Offner H. CD4+FoxP3+ regulatory T-cells in cerebral ischemic stroke. Metab. Brain Dis. 2011, 26:87-90.
90. Ren X.P., Wu J., Wang X., Sartor M.A., Qian J., Jones K., Nicolaou P., Pritchard T.J., Fan G.C. MicroRNA-320 is involved in the regulation of cardiac ischemia/reperfusion injury by targeting heat-shock protein 20. Circulation 2009, 119:2357-2366.
91. Rink C., Khanna S. MicroRNA in ischemic stroke etiology and pathology. Physiol. Genomics 2011, 43:521-528.
92. Saba R., Gushue S., Huzarewich R.L., Manguiat K., Medina S., Robertson C., Booth S.A. MicroRNA 146a (miR-146a) is over-expressed during prior disease and modulates the innate immune response and the microglial activation state. PLoS ONE 2012, 7.
93. Sapojnikova N., Kartvelishvili T., Asatiani N., Zinkevich V., Kalandadze I., Gugutsidze D., Shakarishvili R., Tsiskaridze A. Correlation between MMP-9 and extracellular cytokine HMGB1 in prediction of human ischemic stroke outcome. Biochim. Biophys. Acta 2014, 1842:1379-1384.
94. Schiano C., Vietri M.T., Grimaldi V., Picascia A., De Pascale M.R., Napoli C. Epigenetic-related therapeutic challenges in cardiovascular disease. Trends Pharmacol. Sci. 2015, 36:226-235.
95. Schulze J., Zierath D., Tanzi P., Cain K., Shibata D., Dressel A., Becker K. Severe stroke induces long-lasting alterations of high-mobility group box 1. Stroke 2013, 44:246-248.
96. Selvamani A., Sathyan P., Miranda R.C., Sohrabji F. An antagomir to microRNA Let7f promotes neuroprotection in an ischemic stroke model. PLoS ONE 2012, 7.
97. Soriano-Tárraga C., Jiménez-Conde J., Giralt-Steinhauer E., Mola M., Ois A., Rodríguez-Campello A., Cuadrado-Godia E., Fernández-Cadenas I., Carrera C., Montaner J., Elosua R., Roquer J., GeneStroke "The Spanish Stroke Genetics Consortium" Global DNA methylation of ischemic stroke subtypes. PLoS ONE 2014, 9.
98. Stary C.M., Xu L., Sun X., Ouyang Y.B., White R.E., Leong J., Li J., Xiong X., Giffard R.G. MicroRNA-200c contributes to injury from transient focal cerebral ischemia by targeting Reelin. Stroke 2015, 46:551-556.
99. Stender J.D., Glass C.K. Epigenomic control of the innate immune response. Curr. Opin. Pharmacol. 2013, 13:582-587.
100. Suda S., Katsura K., Kanamaru T., Saito M., Katayamam Y. Valproic acid attenuates ischemia-reperfusion injury in the rat brain through inhibition of oxidative stress and inflammation. Eur. J. Pharmacol. 2013, 707:26-31.
101. Sukumari-Ramesh S., Alleyne C.H., Dhandapani K.M. The histone deacetylase inhibitor Suberoylanilide Hydroxamic Acid (SAHA) confers acute neuroprotection after intracerebral hemorrhage in mice. Transl. Stroke Res. 2015, 10.1007/s12975-015-0421-y.
102. Tan K.S., Armugam A., Sepramaniam S., Lim K.Y., Setyowati K.D., Wang C.W., Jeyaseelan K. Expression profile of MicroRNAs in young stroke patients. PLoS ONE 2009, 4.
103. Unlu S., Tang S., Wang E., Martinez I., Tang D., Bianchi M.E., Zeh H.J., Lotze M.T. Damage associated molecular pattern molecule-induced microRNAs (DAMPmiRs) in human peripheral blood mononuclear cells. PLoS ONE 2012, 7.
104. Wang B., Zhu X., Kim Y., Li J., Huang S., Saleem S., Li R.C., Xu Y., Dore S., Cao W. Histone deacetylase inhibition activates transcription factor Nrf2 and protects against cerebral ischemic damage. Free Radic. Biol. Med. 2012, 52:928-936.
105. Wang L., Tao R., Hancock W.W. Using histone deacetylase inhibitors to enhance Foxp3(+) regulatory T-cell function and induce allograft tolerance. Immunol. Cell Biol. 2009, 87:195-202.
106. Wang Z., Leng Y., Tsai L.K., Leeds P., Chuang D.M. Valproic acid attenuates blood-brain barrier disruption in a rat model of transient focal cerebral ischemia: the roles of HDAC and MMP-9 inhibition. J. Cereb. Blood Flow Metab. 2011, 31:52-57.
107. Wang Z., Tsai L.K., Munasinghe J., Leng Y., Fessler E.B., Chibane F., Leeds P., Chuang D.M. Chronic valproate treatment enhances postischemic angiogenesis and promotes functional recovery in a rat model of ischemic stroke. Stroke 2012, 43:2430-2436.
108. Wei L.K., Sutherland H., Au A., Camilleri E., Haupt L.M., Gan S.H., Griffiths L.R. A potential epigenetic marker mediating serum folate and vitamin B12 levels contributes to the risk of ischemic stroke. Biomed. Res. Int. 2015, 2015:167976.
109. Xu L., Ouyang Y., Xiong X., Stary C.M., Giffard R.G. Post-stroke treatment with miR-181 antagomir reduces injury and improves long-term behavioral recovery in mice after focal cerebral ischemia. Exp. Neurol. 2014, 264C:1-7.
110. Xuan A., Long D., Li J., Ji W., Hong L., Zhang M., Zhang W. Neuroprotective effects of valproic acid following transient global ischemia in rats. Life Sci. 2012, 90:463-468.
111. Yamamoto M., Kondo E., Takeuchi M., Harashima A., Otani T., Tsuji-Takayama K., Yamasaki F., Kumon H., Kibata M., Nakamura S. miR-155, a modulator of FOXO3a protein expression, is underexpressed and cannot be upregulated by stimulation of HOZOT, a line of multifunctional Treg. PLoS One 2011, 6:e16841.
112. Yan J., Greer J.M., Etherington K., Cadigan G.P., Cavanagh H., Henderson R.D., O'Sullivan J.D., Pandian J.D., Read S.J., McCombe P.A. Immune activation in the peripheral blood of patients with acute ischemic stroke. J. Neuroimmunol. 2009, 206:112-117.
113. Yang Q.W., Lu F.L., Zhou Y., Wang L., Zhong Q., Lin S., Xiang J., Li J.C., Fang C.Q., Wang J.Z. HMBG1 mediates ischemia-reperfusion injury by TRIF-adaptor independent Toll-like receptor 4 signaling. J. Cereb. Blood Flow Metab. 2011, 31:593-605.
114. Yildirim F., Gertz K., Kronenberg G., Harms C., Fink K.B., Meisel A., Endres M. Inhibition of histone deacetylation protects wildtype but not gelsolin-deficient mice from ischemic brain injury. Exp. Neurol. 2008, 210:531-542.
115. Yilmaz G., Granger D.N. Leukocyte recruitment and ischemic brain injury. Neruomol. Med. 2010, 12:193-204.
116. Yin K.J., Deng Z., Hamblin M., Xiang Y., Huang H., Zhang J., Jiang X., Wang Y., Chen Y.E. Peroxisome proliferator-activated receptor delta regulation of miR-15a in ischemia-induced cerebral vascular endothelial injury. J. Neurosci. 2010, 30:6398-6408.
117. Yin K.J., Deng Z., Huang H., Hamblin M., Xie C., Zhang J., Chen Y.E. miR-497 regulates neuronal death in mouse brain after transient focal cerebral ischemia. Neurobiol. Dis. 2010, 38:17-26.
118. Zhang L., Li Y.J., Wu X.Y., Hong Z., Wei W.S. MicroRNA-181c negatively regulates the inflammatory response in oxygen-glucose-deprived microglia by targeting Toll-like receptor 4. J. Neurochem. 2014, 132:713-723.
119. Zhang M., Liu F., Jia H., Zhang Q., Yin L., Liu W., Li H., Yu B., Wu J. Inhibition of microRNA let-7i depresses maturation and functional state of dendritic cells in response to lipopolysaccharide stimulation via targeting suppressor of cytokine signaling 1. J. Immunol. 2011, 187:1674-1683.
120. Zhao H., Wang J., Gao L., Wang R., Liu X., Gao Z., Tao Z., Xu C., Song J., Ji X., Luo Y. MiRNA-424 protects against permanent focal cerebral ischemia injury in mice involving suppressing microglia activation. Stroke 2013, 44:1706-1713.
121. Zheng Y., Josefowicz S.Z., Kas A., Chu T.T., Gavin M.A., Rudensky A.Y. Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells. Nature 2007, 445:936-940.
122. Zhu F., Liu J.L., Li J.P., Xiao F., Zhang Z.X., Zhang L. MicroRNA-124 (miR-124) regulates Ku70 expression and is correlated with neuronal death induced by ischemia/reperfusion. J. Mol. Neurosci. 2014, 52:148-155.