| Autor: |
Yu-Hui Lin, Jian Dong, Ying Tang, Huan-Yu Ni, Yu Zhang, Ping Su, Hai-Ying Liang, Meng-Cheng Yao, Hong-Jin Yuan, Dong-Liang Wang, Lei Chang, Hai-Yin Wu, Chun-Xia Luo, Dong-Ya Zhu |
| Předmět: |
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| Zdroj: |
Journal of Neuroscience; 7/12/2017, Vol. 37 Issue 28, p6712-6728, 17p |
| Abstrakt: |
Narrow therapeutic window limits treatments with thrombolysis and neuroprotection for most stroke patients. Widening therapeutic window remains a critical challenge. Understanding the key mechanisms underlying the pathophysiological events in the peri-infarct area where secondary injury coexists with neuroplasticity over days to weeks may offer an opportunity for expanding the therapeutic window. Here we show that ischemia-induced histone deacetylase 2 (HDAC2) upregulation from 5 to 7 d after stroke plays a crucial role. In this window phase, suppressing HDAC2 in the peri-infarct cortex of rodents by HDAC inhibitors, knockdown or knock-out of Hdac2 promoted recovery of motor function from stroke via epigenetically enhancing cells survival and neuroplasticity of surviving neurons as well as reducing neuroinflammation, whereas overexpressing HDAC2 worsened stroke-induced functional impairment of both WT and Hdac2 conditional knock-out mice. More importantly, inhibiting other isoforms of HDACs had no effect. Thus, the intervention by precisely targeting HDAC2 in this window phase is a novel strategy for the functional recovery of stroke survivors. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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