About this Journal Submit a Manuscript Table of Contents
Stroke Research and Treatment
Volume 2013 (2013), Article ID 473416, 13 pages
http://dx.doi.org/10.1155/2013/473416
Review Article

Emerging Molecular Targets for Brain Repair after Stroke

1Cerebrovascular Diseases Unit, Department of Neurology, University Hospital Mutua Terrassa, Terrassa, 08221 Barcelona, Spain
2School of Healthcare Science, Manchester Metropolitan University, Manchester M1 5GD, UK

Received 31 August 2012; Accepted 14 December 2012

Academic Editor: Julio Josë Secades

Copyright © 2013 Jerzy Krupinski and Mark Slevin. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. T. Carmichael, “Translating the frontiers of brain repair to treatments: starting not to break the rules,” Neurobiology of Disease, vol. 37, no. 2, pp. 237–242, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. J. J. Ohab, S. Fleming, A. Blesch, and S. T. Carmichael, “A neurovascular niche for neurogenesis after stroke,” Journal of Neuroscience, vol. 26, no. 50, pp. 13007–13016, 2006. View at Publisher · View at Google Scholar · View at Scopus
  3. S. D. Giovanni, “Molecular targets for axon regeneration: focus on the intrinsic pathways,” Expert Opinion on Therapeutic Targets, vol. 13, no. 12, pp. 1387–1398, 2009. View at Publisher · View at Google Scholar · View at Scopus
  4. M. Slevin, L. Badimon, M. Grau-Olivares et al., “Combining nanotechnology with current biomedical knowledge for the vascular imaging and treatment of atherosclerosis,” Molecular BioSystems, vol. 6, no. 3, pp. 444–450, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. L. I. Benowitz and S. T. Carmichael, “Promoting axonal rewiring to improve outcome after stroke,” Neurobiology of Disease, vol. 37, no. 2, pp. 259–266, 2010. View at Publisher · View at Google Scholar · View at Scopus
  6. S. H. Kreisel, M. G. Hennerici, and H. Bäzner, “Pathophysiology of stroke rehabilitation: the natural course of clinical recovery, use-dependent plasticity and rehabilitative outcome,” Cerebrovascular Diseases, vol. 23, pp. 243–255, 2007.
  7. D. B. Hier, J. Mondlock, and L. R. Caplan, “Behavioral abnormalities after right hemisphere stroke,” Neurology, vol. 33, no. 3, pp. 337–344, 1983. View at Scopus
  8. M. L. Kauhanen, J. T. Korpelainen, P. Hiltunen et al., “Aphasia, depression, and non-verbal cognitive impairment in ischaemic stroke,” Cerebrovascular Diseases, vol. 10, no. 6, pp. 455–461, 2000. View at Scopus
  9. S. T. Carmichael, “Cellular and molecular mechanisms of neural repair after stroke: making waves,” Annals of Neurology, vol. 59, no. 5, pp. 735–742, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. L. I. Benowitz and S. T. Carmichael, “Promoting axonal rewiring to improve outcome after stroke,” Neurobiology of Disease, vol. 37, no. 2, pp. 259–266, 2010. View at Publisher · View at Google Scholar · View at Scopus
  11. P. Chen, D. E. Goldberg, B. Kolb, M. Lanser, and L. I. Benowitz, “Inosine induces axonal rewiring and improves behavioral outcome after stroke,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 13, pp. 9031–9036, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. C. M. Papadopoulos, S. Y. Tsai, T. Alsbiei, T. E. O'Brien, M. E. Schwab, and G. L. Kartje, “Functional recovery and neuroanatomical plasticity following middle cerebral artery occlusion and IN-1 antibody treatment in the adult rat,” Annals of Neurology, vol. 51, no. 4, pp. 433–441, 2002. View at Publisher · View at Google Scholar · View at Scopus
  13. J. Raber, Y. Fan, Y. Matsumori et al., “Irradiation attenuates neurogenesis and exacerbates ischemia-induced deficits,” Annals of Neurology, vol. 55, no. 3, pp. 381–389, 2004. View at Publisher · View at Google Scholar · View at Scopus
  14. J. Krupinski, J. Kaluza, P. Kumar, M. Wang, and S. Kumar, “Prognostic value of blood vessel density in ischaemic stroke,” The Lancet, vol. 342, no. 8873, article 742, 1993. View at Scopus
  15. Z. G. Zhang and M. Chopp, “Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic,” The Lancet Neurology, vol. 8, no. 5, pp. 491–500, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. T. M. Bliss, R. H. Andres, and G. K. Steinberg, “Erratum to Optimizing the success of cell transplantation therapy for stroke,” Neurobiology of Disease, vol. 38, no. 3, p. 495, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. W. Pearce, “Epigenetics: an expanding new piece of the stroke puzzle,” Translational Stroke Research, vol. 2, pp. 243–247, 2011.
  18. D. Botstein and N. Risch, “Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease,” Nature Genetics, vol. 33, pp. 228–237, 2003. View at Publisher · View at Google Scholar · View at Scopus
  19. P. C. Ng and E. F. Kirkness, “Whole genome sequencing,” Methods in Molecular Biology, vol. 628, pp. 215–226, 2010.
  20. M. B. Lanktree, M. Dichgans, and R. A. Hegele, “Advances in genomic analysis of stroke: what have we learned and where are we headed?” Stroke, vol. 41, no. 4, pp. 825–832, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. G. Marnellos, “High-throughput SNP analysis for genetic association studies,” Current Opinion in Drug Discovery and Development, vol. 6, pp. 317–321, 2003.
  22. J. F. Meschia, B. B. Worrall, and S. S. Rich, “Genetic susceptibility to ischemic stroke,” Nature Reviews Neurology, vol. 7, pp. 369–378, 2011.
  23. B. Glaser, “Genetic analysis of complex disease—a roadmap to understanding or a colossal waste of money,” Pediatric Endocrinology Reviews, vol. 7, no. 3, pp. 258–265, 2010. View at Scopus
  24. R. Jaenisch and A. Bird, “Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals,” Nature Genetics, vol. 33, pp. 245–254, 2003. View at Publisher · View at Google Scholar · View at Scopus
  25. J. P. Hamilton, “Epigenetics: principles and practice,” Digestive Diseases, vol. 29, pp. 130–135, 2011.
  26. E. Ballestar, “An introduction to epigenetics,” Advances in Experimental Medicine and Biology, vol. 711, pp. 1–11, 2011.
  27. K. Felekkis, E. Touvana, C. Stefanou, and C. Deltas, “MicroRNAs: a newly described class of encoded molecules that play a role in health and disease,” Hippokratia, vol. 14, no. 4, pp. 236–240, 2010. View at Scopus
  28. Z. W. Pan, Y. J. Lu, and B. F. Yang, “MicroRNAs: a novel class of potential therapeutic targets for cardiovascular diseases,” Acta Pharmacologica Sinica, vol. 31, no. 1, pp. 1–9, 2010. View at Publisher · View at Google Scholar · View at Scopus
  29. N. Liu and E. N. Olson, “MicroRNA regulatory networks in cardiovascular development,” Developmental Cell, vol. 18, no. 4, pp. 510–525, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. Y. Cheng and C. Zhang, “MicroRNA-21 in cardiovascular disease,” Journal of Cardiovascular Translational Research, vol. 3, pp. 251–255, 2010.
  31. E. M. Small and E. N. Olson, “Pervasive roles of microRNAs in cardiovascular biology,” Nature, vol. 469, no. 7330, pp. 336–342, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. K. C. Chen, Y. S. Wang, C. Y. Hu et al., “OxLDL up-regulates microRNA-29b, leading to epigenetic modifications of MMP-2/MMP-9 genes: a novel mechanism for cardiovascular diseases,” FASEB Journal, vol. 25, no. 5, pp. 1718–1728, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. M. Han, J. Toli, and M. Abdellatif, “MicroRNAs in the cardiovascular system,” Current Opinion in Cardiology, vol. 26, no. 3, pp. 181–189, 2011. View at Publisher · View at Google Scholar · View at Scopus
  34. O. Khorram, G. Han, R. Bagherpour et al., “Effect of maternal undernutrition on vascular expression of micro and messenger RNA in newborn and aging offspring,” American Journal of Physiology, vol. 298, no. 5, pp. R1366–R1374, 2010. View at Publisher · View at Google Scholar · View at Scopus
  35. C. Van Solingen, L. Seghers, R. Bijkerk et al., “Antagomir-mediated silencing of endothelial cell specific microRNA-126 impairs ischemia-induced angiogenesis,” Journal of Cellular and Molecular Medicine, vol. 13, no. 8, pp. 1577–1585, 2009. View at Publisher · View at Google Scholar · View at Scopus
  36. Y. Ye, Z. Hu, Y. Lin, C. Zhang, and J. R. Perez-Polo, “Downregulation of microRNA-29 by antisense inhibitors and a PPAR-γagonist protects against myocardial ischaemia-reperfusion injury,” Cardiovascular Research, vol. 87, no. 3, pp. 535–544, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. J. A. Nickerson, G. Krochmalnic, K. M. Wan, and S. Penman, “Chromatin architecture and nuclear RNA,” Proceedings of the National Academy of Sciences of the United States of America, vol. 86, no. 1, pp. 177–181, 1989. View at Scopus
  38. A. Rodríguez-Campos and F. Azorín, “RNA is an integral component of chromatin that contributes to its structural organization,” PLoS ONE, vol. 2, no. 11, Article ID e1182, 2007. View at Publisher · View at Google Scholar · View at Scopus
  39. J. S. Mattick, “A new paradigm for developmental biology,” Journal of Experimental Biology, vol. 210, no. 9, pp. 1526–1547, 2007. View at Publisher · View at Google Scholar · View at Scopus
  40. P. K. Yang and M. I. Kuroda, “Noncoding RNAs and intranuclear positioning in monoallelic gene expression,” Cell, vol. 128, no. 4, pp. 777–786, 2007. View at Publisher · View at Google Scholar · View at Scopus
  41. H. L. Ashe, J. Monks, M. Wijgerde, P. Fraser, and N. J. Proudfoot, “Intergenic transcription and transinduction of the human β-globin locus,” Genes and Development, vol. 11, no. 19, pp. 2494–2509, 1997. View at Scopus
  42. I. Abarrategui and M. S. Krangel, “Noncoding transcription controls downstream promoters to regulate T-cell receptor α recombination,” EMBO Journal, vol. 26, no. 20, pp. 4380–4390, 2007. View at Publisher · View at Google Scholar · View at Scopus
  43. J. C. Peng and G. H. Karpen, “H3K9 methylation and RNA interference regulate nucleolar organization and repeated DNA stability,” Nature Cell Biology, vol. 9, no. 1, pp. 25–35, 2007. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Nowacki, V. Vijayan, Y. Zhou, K. Schotanus, T. G. Doak, and L. F. Landweber, “RNA-mediated epigenetic programming of a genome-rearrangement pathway,” Nature, vol. 451, no. 7175, pp. 153–158, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. S. Schoeftner and M. A. Blasco, “Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II,” Nature Cell Biology, vol. 10, no. 2, pp. 228–236, 2008. View at Publisher · View at Google Scholar · View at Scopus
  46. C. M. Azzalin, P. Reichenbach, L. Khoriauli, E. Giulotto, and J. Lingner, “Telomeric repeat-containing RNA and RNA surveillance factors at mammalian chromosome ends,” Science, vol. 318, no. 5851, pp. 798–801, 2007. View at Publisher · View at Google Scholar · View at Scopus
  47. N. Xu, M. E. Donohoe, S. S. Silva, and J. T. Lee, “Evidence that homologous X-chromosome pairing requires transcription and Ctcf protein,” Nature Genetics, vol. 39, no. 11, pp. 1390–1396, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. L. F. Zhang, K. D. Huynh, and J. T. Lee, “Perinucleolar targeting of the inactive X during S phase: evidence for a role in the maintenance of silencing,” Cell, vol. 129, no. 4, pp. 693–706, 2007. View at Publisher · View at Google Scholar · View at Scopus
  49. P. P. Amaral, M. E. Dinger, T. R. Mercer, and J. S. Mattick, “The eukaryotic genome as an RNA machine,” Science, vol. 319, no. 5871, pp. 1787–1789, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. L. Formisano, K. M. Noh, T. Miyawaki, T. Mashiko, M. V. L. Bennett, and R. S. Zukin, “Ischemic insults promote epigenetic reprogramming of μ opioid receptor expression in hippocampal neurons,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 10, pp. 4170–4175, 2007. View at Publisher · View at Google Scholar · View at Scopus
  51. F. Sato, S. Tsuchiya, S. J. Meltzer, and K. Shimizu, “MicroRNAs and epigenetics,” FEBS Journal, vol. 278, no. 10, pp. 1598–1609, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. A. Dharap, K. Bowen, R. Place, L. C. Li, and R. Vemuganti, “Transient focal ischemia induces extensive temporal changes in rat cerebral MicroRNAome,” Journal of Cerebral Blood Flow and Metabolism, vol. 29, no. 4, pp. 675–687, 2009. View at Publisher · View at Google Scholar · View at Scopus
  53. F. E. Nicolas, H. Pais, F. Schwach et al., “Experimental identification of microRNA-140 targets by silencing and overexpressing miR-140,” RNA, vol. 14, no. 12, pp. 2513–2520, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. K. Jeyaseelan, K. Y. Lim, and A. Armugam, “MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion,” Stroke, vol. 39, no. 3, pp. 959–966, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. H. Xin, Y. Li, B. Buller, et al., “Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth,” Stem Cells, vol. 30, no. 7, pp. 1556–1564, 2012.
  56. X. Zhao, X. He, X. Han et al., “MicroRNA-mediated control of oligodendrocyte differentiation,” Neuron, vol. 65, no. 5, pp. 612–626, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. T. R. Mercer, M. E. Dinger, and J. S. Mattick, “Long non-coding RNAs: insights into functions,” Nature Reviews Genetics, vol. 10, no. 3, pp. 155–159, 2009. View at Publisher · View at Google Scholar · View at Scopus
  58. T. R. Mercer, M. E. Dinger, J. Mariani, K. S. Kosik, M. F. Mehler, and J. S. Mattick, “Noncoding RNAs in long-term memory formation,” Neuroscientist, vol. 14, no. 5, pp. 434–445, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. J. Rashidian, G. Iyirhiaro, H. Aleyasin et al., “Multiple cyclin-dependent kinases signals are critical mediators of ischemia/hypoxic neuronal death in vitro and in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 39, pp. 14080–14085, 2005. View at Publisher · View at Google Scholar · View at Scopus
  60. N. Ishii, K. Ozaki, H. Sato et al., “Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction,” Journal of Human Genetics, vol. 51, no. 12, pp. 1087–1099, 2006. View at Publisher · View at Google Scholar · View at Scopus
  61. I. A. Qureshi and M. F. Mehler, “The emerging role of epigenetics in stroke: II. RNA regulatory circuitry,” Archives of Neurology, vol. 67, no. 12, pp. 1435–1441, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. P. L. Peng, X. Zhong, W. Tu et al., “ADAR2-dependent RNA editing of AMPA receptor subunit GluR2 determines vulnerability of neurons in forebrain ischemia,” Neuron, vol. 49, no. 5, pp. 719–733, 2006. View at Publisher · View at Google Scholar · View at Scopus
  63. M. J. Blow, R. J. Grocock, S. van Dongen et al., “RNA editing of human microRNAs,” Genome Biology, vol. 7, no. 4, article R27, 2006. View at Publisher · View at Google Scholar · View at Scopus
  64. Y. Kawahara, B. Zinshteyn, T. P. Chendrimada, R. Shiekhattar, and K. Nishikura, “RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer—TRBP complex,” EMBO Reports, vol. 8, no. 8, pp. 763–769, 2007. View at Publisher · View at Google Scholar · View at Scopus
  65. V. Shani, Y. Bromberg, O. Sperling, and E. Zoref-Shani, “Involvement of Src tyrosine kinases (SFKs) and of focal adhesion kinase (FAK) in the injurious mechanism in rat primary neuronal cultures exposed to chemical ischemia,” Journal of Molecular Neuroscience, vol. 37, no. 1, pp. 50–59, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. A. Selvamani, P. Sathyan, R. Miranda, and F. Sohrabji, “An antagomir to MicroRNA Let7f promotes neuroprotection in an ischemic stroke model,” PLoS ONE, vol. 7, no. 2, Article ID e32662. View at Publisher · View at Google Scholar
  67. S. G. Conticello, “The AID/APOBEC family of nucleic acid mutators,” Genome Biology, vol. 9, no. 6, article 229, 2008. View at Publisher · View at Google Scholar · View at Scopus
  68. K. Silander, M. Alanne, K. Kristiansson et al., “Gender differences in genetic risk profiles for cardiovascular disease,” PLoS ONE, vol. 3, no. 10, Article ID e3615, 2008. View at Publisher · View at Google Scholar · View at Scopus
  69. Y. J. Wang, X. Wang, H. Zhang et al., “Expression and regulation of antiviral protein APOBEC3G in human neuronal cells,” Journal of Neuroimmunology, vol. 206, no. 1-2, pp. 14–21, 2009. View at Publisher · View at Google Scholar · View at Scopus
  70. J. S. Mattick and M. F. Mehler, “RNA editing, DNA recoding and the evolution of human cognition,” Trends in Neurosciences, vol. 31, no. 5, pp. 227–233, 2008. View at Publisher · View at Google Scholar · View at Scopus
  71. J. A. Watson, C. J. Watson, A. Mccann, and J. Baugh, “Epigenetics, the epicenter of the hypoxic response,” Epigenetics, vol. 5, no. 4, pp. 293–296, 2010. View at Publisher · View at Google Scholar · View at Scopus
  72. N. Sang and S. Chen, “Histone deacetylase inhibitors: the epigenetic therapeutics that repress hypoxia-inducible factors,” Journal of Biomedicine and Biotechnology, vol. 2011, Article ID 197946, 2011. View at Publisher · View at Google Scholar · View at Scopus
  73. S. Biswas, S. Roy, J. Banerjee et al., “Hypoxia inducible microRNA 210 attenuates keratinocyte proliferation and impairs closure in a murine model of ischemic wounds,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 15, pp. 6976–6981, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. S. Y. Chan and J. Loscalzo, “MicroRNA-210: a unique and pleiotropic hypoxamir,” Cell Cycle, vol. 9, no. 6, pp. 1072–1083, 2010. View at Scopus
  75. J. A. Saugstad, “MicroRNAs as effectors of brain function with roles in ischemia and injury, neuroprotection, and neurodegeneration,” Journal of Cerebral Blood Flow & Metabolism, vol. 30, pp. 1564–1576, 2010.
  76. C. H. Hsieh, J. C. Jeng, S. F. Jeng, C. J. Wu, T. H. Lu, P. C. Liliang, et al., “MicroRNA profiling in ischemic injury of the gracilis muscle in rats,” BMC Musculoskeletal Disorders, vol. 11, article 123, 2010.
  77. C. Stowell, L. Wang, B. Arbogast et al., “Retinal proteomic changes under different ischemic conditions—Implication of an epigenetic regulatory mechanism,” International Journal of Physiology, Pathophysiology and Pharmacology, vol. 2, no. 2, pp. 148–160, 2010. View at Scopus
  78. P. Fasanaro, S. Greco, M. Ivan, M. C. Capogrossi, and F. Martelli, “microRNA: emerging therapeutic targets in acute ischemic diseases,” Pharmacology and Therapeutics, vol. 125, no. 1, pp. 92–104, 2010. View at Publisher · View at Google Scholar · View at Scopus
  79. C. Yin, F. N. Salloum, and R. C. Kukreja, “A novel role of microRNA in late preconditioning: upregulation of endothelial nitric oxide synthase and heat shock protein 70,” Circulation Research, vol. 104, no. 5, pp. 572–575, 2009. View at Publisher · View at Google Scholar · View at Scopus
  80. H. W. Kim, H. K. Haider, S. Jiang, and M. Ashraf, “Ischemic preconditioning augments survival of stem cells via miR-210 expression by targeting caspase-8-associated protein 2,” Journal of Biological Chemistry, vol. 284, no. 48, pp. 33161–33168, 2009. View at Publisher · View at Google Scholar · View at Scopus
  81. T. A. Lusardi, C. D. Farr, C. L. Faulkner et al., “Ischemic preconditioning regulates expression of microRNAs and a predicted target, MeCP2, in mouse cortex,” Journal of Cerebral Blood Flow and Metabolism, vol. 30, no. 4, pp. 744–756, 2010. View at Publisher · View at Google Scholar · View at Scopus
  82. Y. Cheng, P. Zhu, J. Yang et al., “Ischaemic preconditioning-regulated miR-21 protects heart against ischaemia/reperfusion injury via anti-apoptosis through its target PDCD4,” Cardiovascular Research, vol. 87, no. 3, pp. 431–439, 2010. View at Publisher · View at Google Scholar · View at Scopus
  83. A. M. Jose and C. P. Hunter, “Transport of sequence-specific RNA interference information between cells,” Annual Review of Genetics, vol. 41, pp. 305–330, 2007. View at Publisher · View at Google Scholar · View at Scopus
  84. G. Faraco, T. Pancani, L. Formentini et al., “Pharmacological inhibition of histone deacetylases by suberoylanilide hydroxamic acid specifically alters gene expression and reduces ischemic injury in the mouse brain,” Molecular Pharmacology, vol. 70, no. 6, pp. 1876–1884, 2006. View at Publisher · View at Google Scholar · View at Scopus
  85. Y. Takami, H. Nakagami, R. Morishita et al., “Ubiquitin carboxyl-terminal hydrolase L1, a novel deubiquitinating enzyme in the vasculature, attenuates NF-κB activation,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 10, pp. 2184–2190, 2007. View at Publisher · View at Google Scholar · View at Scopus
  86. R. Setsuie and K. Wada, “The functions of UCH-L1 and its relation to neurodegenerative diseases,” Neurochemistry International, vol. 51, no. 2–4, pp. 105–111, 2007. View at Publisher · View at Google Scholar · View at Scopus
  87. Y. C. Lin, J. H. Lin, C. W. Chou, Y. F. Chang, S. H. Yeh, and C. C. Chen, “Statins increase p21 through inhibition of histone deacetylase activity and release of promoter-associated HDAC1/2,” Cancer Research, vol. 68, no. 7, pp. 2375–2383, 2008. View at Publisher · View at Google Scholar · View at Scopus
  88. A. Dharap, K. Bowen, R. Place, L. C. Li, and R. Vemuganti, “Transient focal ischemia induces extensive temporal changes in rat cerebral MicroRNAome,” Journal of Cerebral Blood Flow and Metabolism, vol. 29, no. 4, pp. 675–687, 2009. View at Publisher · View at Google Scholar · View at Scopus
  89. K. J. Yin, Z. Deng, H. Huang et al., “miR-497 regulates neuronal death in mouse brain after transient focal cerebral ischemia,” Neurobiology of Disease, vol. 38, no. 1, pp. 17–26, 2010. View at Publisher · View at Google Scholar · View at Scopus
  90. J. A. Saugstad, “MicroRNAs as effectors of brain function with roles in ischemia and injury, neuroprotection, and neurodegeneration,” Journal of Cerebral Blood Flow and Metabolism, vol. 30, no. 9, pp. 1564–1576, 2010. View at Publisher · View at Google Scholar · View at Scopus
  91. F. R. Sharp, G. C. Jickling, B. Stamova et al., “Molecular markers and mechanisms of stroke: RNA studies of blood in animals and humans,” Journal of Cerebral Blood Flow and Metabolism, vol. 31, pp. 1513–1531, 2011. View at Publisher · View at Google Scholar · View at Scopus
  92. P. Landry, I. Plante, D. L. Ouellet, M. P. Perron, G. Rousseau, and P. Provost, “Existence of a microRNA pathway in anucleate platelets,” Nature Structural and Molecular Biology, vol. 16, no. 9, pp. 961–966, 2009. View at Publisher · View at Google Scholar · View at Scopus
  93. K. Jeyaseelan, K. Y. Lim, and A. Armugam, “MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion,” Stroke, vol. 39, no. 3, pp. 959–966, 2008. View at Publisher · View at Google Scholar · View at Scopus
  94. K. S. Tan, A. Armugam, S. Sepramaniam et al., “Expression profile of microRNAs in young stroke patients,” PLoS ONE, vol. 4, no. 11, Article ID e7689, 2009. View at Publisher · View at Google Scholar · View at Scopus
  95. D. Z. Liu, Y. Tian, B. P. Ander et al., “Brain and blood microRNA expression profiling of ischemic stroke, intracerebral hemorrhage, and kainate seizures,” Journal of Cerebral Blood Flow and Metabolism, vol. 30, no. 1, pp. 92–101, 2010. View at Publisher · View at Google Scholar · View at Scopus
  96. R. Ji, Y. Cheng, J. Yue et al., “MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation,” Circulation Research, vol. 100, no. 11, pp. 1579–1588, 2007. View at Publisher · View at Google Scholar · View at Scopus
  97. Z. Zhang, X. Yang, S. Zhang, X. Ma, and J. Kong, “BNIP3 upregulation and EndoG translocation in delayed neuronal death in stroke and in hypoxia,” Stroke, vol. 38, no. 5, pp. 1606–1613, 2007. View at Publisher · View at Google Scholar · View at Scopus
  98. T. Miyawaki, D. Ofengeim, K. M. Noh et al., “The endogenous inhibitor of Akt, CTMP, is critical to ischemia-induced neuronal death,” Nature Neuroscience, vol. 12, no. 5, pp. 618–626, 2009. View at Publisher · View at Google Scholar · View at Scopus
  99. M. Wood, H. Yin, and G. McClorey, “Modulating the expression of disease genes with RNA-based therapy,” PLoS Genetics, vol. 3, no. 6, Article ID e109, 2007. View at Publisher · View at Google Scholar · View at Scopus
  100. A. C. Yan and M. Levy, “Aptamers and aptamer targeted delivery,” RNA Biology, vol. 6, no. 3, pp. 316–320, 2009. View at Scopus
  101. A. B. Gyorgy, M. Szemes, C. De Juan Romero, V. Tarabykin, and D. V. Agoston, “SATB2 interacts with chromatin-remodeling molecules in differentiating cortical neurons,” European Journal of Neuroscience, vol. 27, no. 4, pp. 865–873, 2008. View at Publisher · View at Google Scholar · View at Scopus
  102. T. R. Mercer, M. E. Dinger, S. M. Sunkin, M. F. Mehler, and J. S. Mattick, “Specific expression of long noncoding RNAs in the mouse brain,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 2, pp. 716–721, 2008. View at Publisher · View at Google Scholar · View at Scopus
  103. I. A. Qureshi and M. F. Mehler, “Regulation of non-coding RNA networks in the nervous system-What's the REST of the story?” Neuroscience Letters, vol. 466, no. 2, pp. 73–80, 2009. View at Publisher · View at Google Scholar · View at Scopus
  104. A. Calderone, T. Jover, K. M. Noh et al., “Ischemic insults derepress the gene silencer REST in neurons destined to die,” Journal of Neuroscience, vol. 23, no. 6, pp. 2112–2121, 2003. View at Scopus
  105. L. Formisano, K. M. Noh, T. Miyawaki, T. Mashiko, M. V. Bennett, and R. S. Zukin, “Ischemic insults promote epigenetic reprogramming of μopioid receptor expression in hippocampal neurons,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 10, pp. 4170–4175, 2007.
  106. G. Shan, Y. Li, J. Zhang et al., “A small molecule enhances RNA interference and promotes microRNA processing,” Nature Biotechnology, vol. 26, no. 8, pp. 933–940, 2008. View at Publisher · View at Google Scholar · View at Scopus
  107. K. D. Mansfield and J. D. Keene, “The ribonome: a dominant force in co-ordinating gene expression,” Biology of the Cell, vol. 101, no. 3, pp. 169–181, 2009. View at Publisher · View at Google Scholar · View at Scopus
  108. D. J. DeGracia, J. T. Jamison, J. J. Szymanski, and M. K. Lewis, “Translation arrest and ribonomics in post-ischemic brain: layers and layers of players,” Journal of Neurochemistry, vol. 106, no. 6, pp. 2288–2301, 2008. View at Publisher · View at Google Scholar · View at Scopus
  109. M. E. Dinger, T. R. Mercer, and J. S. Mattick, “RNAs as extracellular signaling molecules,” Journal of Molecular Endocrinology, vol. 40, no. 3-4, pp. 151–159, 2008. View at Publisher · View at Google Scholar · View at Scopus
  110. N. R. Smalheiser, “Exosomal transfer of proteins and RNAs at synapses in the nervous system,” Biology Direct, vol. 2, article 35, 2007. View at Publisher · View at Google Scholar · View at Scopus
  111. H. Liu, N. Mulholland, H. Fu, and K. Zhao, “Cooperative activity of BRG1 and Z-DNA formation in chromatin remodeling,” Molecular and Cellular Biology, vol. 26, no. 7, pp. 2550–2559, 2006. View at Publisher · View at Google Scholar · View at Scopus
  112. G. Wang and K. M. Vasquez, “Z-DNA, an active element in the genome,” Frontiers in Bioscience, vol. 12, no. 12, pp. 4424–4438, 2007. View at Publisher · View at Google Scholar · View at Scopus