Table 1.
Summary of studies employing epigenetic modulators in spinal cord or optic nerve injury models
| Agents | Injury model | Species | Target | Treatment | In vivo effects |
|---|---|---|---|---|---|
| Valproic acid | T8 moderate contusion | Rat | Class I HDACs | 300 mg/kg i.p., twice daily immediately after injury for 2 wks | - ↑ AcH3, AcH4, Bcl-2, HSP-70 - Decreased apoptosis - Improved functional recovery (Lv et al., 2011) |
| Valproic acid | T9 moderate contusion | Rat | Class I HDACs | 300 mg/kg i.p., twice daily, starting 8 h post injury for 1wk | - ↑AcH3, BDNF, GDNF - Reduced apoptosis - Smaller lesion volume - Improved functional recovery (Lv et al., 2012) |
| Valproic acid | T9-T10 moderate contusion | Rat | Class I HDACs | 150 or 300 mg/kg s.c., immediately after injury then every 12 h for 5 d | - ↑ H3K9Ac - ↓ MMP-9, blood-spinal cord barrier breakdown, inflammation, apoptosis, lesion volume - Improved functional recovery (Lee et al., 2012) |
| Valproic acid | T9 clip compression | Rat | Class I HDACs | 200 mg/kg i.p., twice daily for 1 wk | - ↑ AcH3K, AcH3K18 - ↓ ED-1+ macrophages - Smaller lesion volume - Improved functional recovery (Yu et al., 2012) |
| Valproic acid | T9-T10 very severe contusion | Rat | Class I HDACs | 500 ng/d, osmotic pump for 3 d | - ↑ SOD - ↓ macrophages/microglia, astrocytes, P2X4R - Preserved tissue and nerve fibers - Improved functional recovery (Lu et al., 2013) |
| MS-275 | C5 dorsal column transection | Mouse | HDAC1 & 3 | 12.5 mg/kg s.c., immediately after injury, then daily for 4 d | - ↑ AcH4 - ↑ RAG transcription - Enhanced sensory axon regeneration (Finelli et al., 2013) |
| AAVP/CAF | T9-T10 dorsal hemi-crush | Mouse | PCAF | Sciatic nerve injection, 2 wks prior to injury | - ↑ H3K9Ac - ↑ RAG expression - Enhanced sensory axon regeneration (Puttagunta et al., 2014) |
| AVp300 | Optic nerve crush | Rat | p300 | Intraocular injection at time of injury | - ↑ Ac-p53, -C/EBP, H3K18Ac - ↑ RAG expression - Enhanced optic nerve regeneration - No effect on RGC survival (Gaub et al., 2011) |
| TSA | Optic nerve crush | Rat | Class I/II HDACs | 1, 10 or 100 ng/mL, injected into the vitreous at the time of injury. | - Improved RGC survival - No effect on axon regeneration (Gaub et al., 2011) |