PMID- 23793904 OWN - NLM STAT- MEDLINE DCOM- 20140310 LR - 20211021 IS - 1573-6903 (Electronic) IS - 0364-3190 (Linking) VI - 38 IP - 9 DP - 2013 Sep TI - Effect of HDAC inhibitors on neuroprotection and neurite outgrowth in primary rat cortical neurons following ischemic insult. PG - 1921-34 LID - 10.1007/s11064-013-1098-9 [doi] AB - Histone deacetylase inhibitors (HDACi)-valproic acid (VPA) and trichostatin A (TSA) promote neurogenesis, neurite outgrowth, synaptic plasticity and neuroprotection. In this study, we investigated whether VPA and TSA promote post-ischemic neuroprotection and neuronal restoration in rat primary cortical neurons. On 6 days in vitro (DIV), cortical neurons were exposed to oxygen-glucose deprivation for 90 min. Cells were returned to normoxic conditions and cultured for 1, 3, or 7 days with or without VPA and TSA. Control cells were cultured in normoxic conditions only. On 7, 9, and 13 DIV, cells were measured neurite outgrowth using the Axiovision program and stained with Tunel staining kit. Microtubule associated protein-2 immunostaining and tunel staining showed significant recovery of neurite outgrowth and post-ischemic neuronal death by VPA or TSA treatment. We also determined levels of acetylated histone H3, PSD95, GAP 43 and synaptophysin. Significant increases in all three synaptic markers and acetylated histone H3 were observed relative to non-treated cells. Post-ischemic HDACi treatment also significantly raised levels of brain derived neurotrophic factor (BDNF) expression and secreted BDNF. Enhanced BDNF expression by HDACi treatment might have been involved in the post-ischemic neuroprotection and neuronal restorative effects. Our findings suggest that both VPA and TSA treatment during reoxygenation after ischemia may help post-ischemic neuroprotection and neuronal regeneration via increased BDNF expression and activation. FAU - Hasan, Mohammad Rakibul AU - Hasan MR AD - Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul, 143-701, Korea. FAU - Kim, Ji-Hye AU - Kim JH FAU - Kim, Youn Jung AU - Kim YJ FAU - Kwon, Kyoung Ja AU - Kwon KJ FAU - Shin, Chan Young AU - Shin CY FAU - Kim, Hahn Young AU - Kim HY FAU - Han, Seol-Heui AU - Han SH FAU - Choi, Dong-Hee AU - Choi DH FAU - Lee, Jongmin AU - Lee J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130622 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (DNA Primers) RN - 0 (Histone Deacetylase Inhibitors) RN - 0 (Neuroprotective Agents) SB - IM MH - Animals MH - Base Sequence MH - Brain-Derived Neurotrophic Factor/metabolism MH - DNA Primers MH - Female MH - Histone Deacetylase Inhibitors/*pharmacology MH - *Neurites MH - Neuroprotective Agents/*pharmacology MH - Pregnancy MH - Rats MH - Rats, Sprague-Dawley MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2013/06/25 06:00 MHDA- 2014/03/13 06:00 CRDT- 2013/06/25 06:00 PHST- 2013/02/26 00:00 [received] PHST- 2013/06/13 00:00 [accepted] PHST- 2013/05/28 00:00 [revised] PHST- 2013/06/25 06:00 [entrez] PHST- 2013/06/25 06:00 [pubmed] PHST- 2014/03/13 06:00 [medline] AID - 10.1007/s11064-013-1098-9 [doi] PST - ppublish SO - Neurochem Res. 2013 Sep;38(9):1921-34. doi: 10.1007/s11064-013-1098-9. Epub 2013 Jun 22.