The Effect of Histone Deacetylase Inhibitors Panobinostat or Entinostat on Motor Recovery in Mice After Ischemic Stroke.
The Effect of Histone Deacetylase Inhibitors Panobinostat or Entinostat on Motor Recovery in Mice After Ischemic Stroke.
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DOI：
10.1007/s12017-021-08647-1
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发表时间：
2021-12
影响因子：
3.5
通讯作者：
Karamyan VT
中科院分区：
文献类型：
--
作者：
Al Shoyaib A;Alamri FF;Syeara N;Jayaraman S;Karamyan ST;Arumugam TV;Karamyan VT
在本研究中，我们采用严格且临床相关的实验设计和分析标准，研究了组蛋白脱乙酰酶 (HDAC) 抑制剂帕比司他和恩替司他促进雄性小鼠光血栓性中风后运动功能恢复的潜力。 Panobinostat是一种泛HDAC抑制剂，是FDA批准用于治疗某些癌症的药物，而entinostat是一种处于临床研究后期的I类HDAC抑制剂。从中风后第 5 天到第 15 天开始，每隔一天给药一次（帕比司他 — 3 或 10 毫克/公斤；恩替司他 — 1.7 或 5 毫克/公斤）。为了模仿当前中风幸存者的护理标准，即身体康复，从中风后第 9 天到第 41 天，动物在轮子上跑步（每天 2 小时）。预定的主要终点是在网格行走和圆柱测试中的两项自发运动行为任务中测量的运动恢复。此外，我们评估了整个研究过程中的跑步距离和速度，以及研究结束时内侧无颗粒皮层 (AGm) 和梗塞体积中小清蛋白阳性神经元的数量。两项感觉运动测试都表明，体育锻炼与任何一种药物的结合并不会显着影响中风后小鼠的运动恢复。伴随着 AGm 中记录的小清蛋白阳性神经元的变化以及实验组之间可比较的梗塞体积，同时在药物治疗的动物的梗塞周围皮层中观察到乙酰化组蛋白 3 的剂量依赖性增加。我们的观察表明，附加帕比司他或恩替司他治疗加上有限的身体康复不太可能为患有运动功能障碍的中风幸存者提供治疗方式。
Using rigorous and clinically relevant experimental design and analysis standards, in this study, we investigated the potential of histone deacetylase (HDAC) inhibitors panobinostat and entinostat to enhance recovery of motor function after photothrombotic stroke in male mice. Panobinostat, a pan-HDAC inhibitor, is a FDA-approved drug for certain cancers, whereas entinostat is a class-I HDAC inhibitor in late stage of clinical investigation. The drugs were administered every other day (panobinostat—3 or 10 mg/kg; entinostat—1.7 or 5 mg/kg) starting from day 5 to 15 after stroke. To imitate the current standard of care in stroke survivors, i.e., physical rehabilitation, the animals run on wheels (2 h daily) from post-stroke day 9 to 41. The predetermined primary end point was motor recovery measured in two tasks of spontaneous motor behaviors in grid-walking and cylinder tests. In addition, we evaluated the running distance and speed throughout the study, and the number of parvalbumin-positive neurons in medial agranular cortex (AGm) and infarct volumes at the end of the study. Both sensorimotor tests revealed that combination of physical exercise with either drug did not substantially affect motor recovery in mice after stroke. This was accompanied by negligible changes of parvalbumin-positive neurons recorded in AGm and comparable infarct volumes among experimental groups, while dose-dependent increase in acetylated histone 3 was observed in peri-infarct cortex of drug-treated animals. Our observations suggest that add-on panobinostat or entinostat therapy coupled with limited physical rehabilitation is unlikely to offer therapeutic modality for stroke survivors who have motor dysfunction.
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DOI：
10.2147/dddt.s56071
发表时间：
2015
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Fluri F;Schuhmann MK;Kleinschnitz C
通讯作者：
Kleinschnitz C
影响因子：
6.1
作者：
Karamyan VT
通讯作者：
Karamyan VT
DOI：
10.3233/jhd-160226
发表时间：
2016-12-15
期刊：
Journal of Huntington's disease
影响因子：
--
作者：
Chopra V;Quinti L;Khanna P;Paganetti P;Kuhn R;Young AB;Kazantsev AG;Hersch S
通讯作者：
Hersch S
影响因子：
3.7
作者：
Hennika T;Hu G;Olaciregui NG;Barton KL;Ehteda A;Chitranjan A;Chang C;Gifford AJ;Tsoli M;Ziegler DS;Carcaboso AM;Becher OJ
通讯作者：
Becher OJ
DOI：
10.1124/jpet.107.120188
发表时间：
2007-06-01
影响因子：
3.5
作者：
Kim, Hyeon Ju;Rowe, Michael;Chuang, De-Maw
通讯作者：
Chuang, De-Maw