Table 4.
Therapeutic Potential of Epigenetic Modulators in Ischemic Stroke
| Model | Therapeutic Potential | Modification | Citation |
|---|---|---|---|
| 129/SV mice, MCAO | 5’-aza-dC as well as TSA reduced infarct size | DNA methylation | Endres et al., 2000 |
| SD rats, HI | 5’-aza-dC protects against nicotine-induced susceptibility | DNA methylation | Li et al., 2013 |
| Wistar rats, photothrombotic stroke | TST or TST+5’-aza-dC upregulates BDNF and improves neurological score | DNA methylation | Choi et al., 2018 |
| HT22 cells | 5’aza-dC downregulates DNMT1, induces S phase arrest, and inhibits early apoptosis while promoting late apoptosis | DNA methylation | Yang et al., 2017 |
| ICR mice, MCAO | SC1 reverses mitochondrial 5hmC upregulation by inhibiting TET2 leading to increased levels of ATP | DNA hydroxymethylation | Ji et al., 2018 |
| C57 mice, MCAO | Overexpression of Polycomb proteins SCMH1 and BMI1 is neuroprotective | Polycomb protein | Stapels et al., 2010 |
| Cortical neurons, CA and 3-NP | Overexpression of BMI1 acts by way of antioxidant genes to provide protection | Polycomb protein | Abdouh et al., 2012 |
| Wistar rats, 4-VO | VPA confers inflammatory protection and improves functional recovery | Histone acetylation | Xuan et al., 2012 |
| SD rats, MCAO | VPA, SB, or TSA prevent hypoacetylation of H3, prevent inflammation, and reduce infarct volume | Histone acetylation | Kim et al., 2007 |
| C57 mice, MCAO | SAHA reverses H3 hypoacetylation, promotes Hsp70 and BCL-2, and reduces infarct volume | Histone acetylation | Faraco et al., 2006 |
| C57 mice, HI | 4-PBA improves functional recovery via protection from apoptotic mechanisms | Histone acetylation | Qi et al., 2004 |
| Optic nerves, OGD | SAHA and MS-275 rescue white matter | Histone acetylation | Baltan et al., 2011 |
| Cortical neurons | Despite reducing ischemic infarct, HDAC inhibitors are cytotoxic to cells they do not protect | Histone acetylation | Langley et al., 2008 |
| SD rats, forebrain ischemia | MiR-181a antagomir decreases CA1 neuron death | MiRNA | Moon et al., 2013 |
| Primary astrocytes, GD | MiR-181a inhibition decreases apoptosis via upregulation of BCL-2 and MCL-1 | MiRNA | Ouyang et al., 2012 |
| C57 mice, MCAO | Overexpression of miR-124 is neuroprotective by downregulation of REST and Usp-14 | MiRNA | Doeppner et al., 2013 |
| C57 mice, MCAO | MiR-124 agomir reduces infarct volume | MiRNA | Sun et al., 2013 |
| C57 mice, MCAO | Liposomated miR-124 reduces inflammatory markers and infarct volume | MiRNA | Hamzei et al., 2016 |
| PC12 cells, OGD | MiR-124 mimic activates the PI3K/AKT pathway and reduces apoptosis | MiRNA | Wang et al., 2017 |
| SD rats, MCAO | MiR-124 knockdown or miR-124 antagomir is neuroprotective | MiRNA | Zhu et al., 2014 |
| SD rats, MCAO | MiR-155 inhibition reduces infarct volume | MiRNA | Xing et al., 2016 |
| C57 mice, MCAO | MiR-155 inhibition reduces infarct volume | MiRNA | Caballero-Garrido et al., 2015 |
| Oligodendrocyte precursors | MiR-146a overexpression increases myelination | MiRNA | Liu et al., 2017 |
| Neuroblastoma cells, OGD | MiR-146a inhibition prevents apoptosis via Fblx10 upregulation | MiRNA | Li et al., 2017 |
| C57 mice, MCAO | Lentiviral overexpression of miR-424 is neuroprotective via cell cycle arrest and inflammatory suppression | MiRNA | Zhao et al., 2013 |
| C57 mice, MCAO | MiR-424 antagomir is neuroprotective by way of oxidative stress prevention | MiRNA | Liu et al., 2015 |
| C57 mice, MCAO | The inhibitor TAT-p53-DBD270–281 uncouples MEG3 from p53 to provide neuroprotection | LncRNA | Yan et al., 2016 |
| SHR rats, MCAO | Knockdown of FosDT derepresses REST genes and improves functional recovery | LncRNA | Mehta et al., 2015 |
| C57 mice, MCAO | MiR-181a antagomir reduces inflammation and infarct size while improving behavioral recovery | MiRNA | Xu et al., 2015 |
| PC12 cells, OGD | MiR-210 overexpression protects against apoptotic events | MiRNA | Qiu et al., 2013 |
| C57 mice, MCAO | MiR-210 overexpression increases BDNF and improves neurological scores | MiRNA | Zeng et al., 2016 |
| SD rats, MCAO | MiR-210 promotes vagus nerve stimulation-mediated recovery | MiRNA | Jiang et al., 2015 |
| C57 mice, MCAO | Inhibition of miR-210 attenuates inflammatory response | MiRNA | Huang et al., 2018 |
| C57 mice, MCAO | Inhibition of MALAT1 is neuroprotective by way of decreasing autophagy | LncRNA | Guo et al., 2017 |
| SD rats, MCAO | Sh-MEG3 administration improves functional recovery and promotes angiogenesis | LncRNA | Liu et al., 2017 |
| Human serum | Peng et al. used let-7e to predict acute stroke with 73.4% sensitivity and 82.8% specificity | MiRNA | Peng et al., 2015 |
| C57 mice, MCAO | MEG3 knockdown prevents apoptosis | LncRNA | Yan et al., 2017 |
| BV2 cells, OGD | H19 knockdown reduces inflammation to provide neuroprotection | LncRNA | Wang et al., 2017 |
| Neuroblastoma cells, OGD | Overexpression of N1LR prevents apoptosis | LncRNA | Wu et al., 2017 |
| C57 mice, MCAO and cortical neurons, OGD | Knockdown of GAS5 is neuroprotective via decreased competition with miR-137 | LncRNA, miRNA | Chen et al., 2018 |