The present investigation evaluates the protective effect of vorinostat on neuronal cells in the traumatic brain injury (TBI) and also postulates the possible mechanism of its action. Marmarou's weight-drop model was used to induce the TBI. Further, animals were treated with vorinostat 100 mg/kg intraperitoneally 30 min before the TBI induction. Neurological score and brain water content were determined in all the groups and thereafter oxidative stress parameters and adenosine triphosphate (ATP) content were determined in the neuronal tissues of TBI mice. Western blot assay and reverse transcription polymerase chain reaction (RT-PCR) was performed for the determination of the expression of several proteins in the neuronal tissues. Moreover, immunohistochemical staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was also done on the neuronal tissues of TBI mice. Data of the study reveal that treatment with vorinostat significantly reduces the altered level of grip test scores and water content in the brain of traumatic injured mice. Moreover, the altered level of oxidative stress parameters, translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and ATP content was attenuated by treating TBI mice with vorinostat. Also treatment with vorinostat ameliorates the altered expression of p-Akt, NF-B, iNOS and caspase by the western blot assay in the neuronal tissue of TBI mice and mRNA level of HO-1 and NQO-1 significantly enhanced in vorinostat compared to the negative control group. Furthermore, the TUNEL assay also reveals that the apoptosis of neuronal cells was significantly (p < 0.01) reduced in the vorinostat-treated group compared to the negative control group. The present study concludes that vorinostat protects the neuronal injury in TBI mice by reducing the altered level of oxidative stress and inflammatory response.

中文翻译：

---

伏立诺他：组蛋白脱乙酰基酶（HDAC）抑制剂可通过诱导iNOS / Nrf2 / ARE途径缓解颅脑损伤。

本研究评估了伏立诺他对脑外伤（TBI）中神经元细胞的保护作用，并推测了其作用的可能机制。使用Marmarou的体重减轻模型来诱发TBI。此外，在TBI诱导前30分钟腹膜内用伏立诺他100mg / kg治疗动物。测定所有组的神经学评分和脑含水量，然后测定TBI小鼠神经元组织的氧化应激参数和三磷酸腺苷（ATP）含量。进行了蛋白质印迹分析和逆转录聚合酶链反应（RT-PCR），以确定神经元组织中几种蛋白质的表达。此外，还对TBI小鼠的神经元组织进行了免疫组织化学染色和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）分析。该研究数据表明，用伏立诺他治疗可显着降低创伤性受伤小鼠大脑的握力测验分数和含水量的改变水平。此外，通过用伏立诺他治疗TBI小鼠，可以减轻氧化应激参数水平的改变，核因子红系2相关因子2（Nrf2）的易位和ATP含量的降低。此外，通过western blot分析，用伏立诺他治疗可改善TBI小鼠神经元组织中p-Akt，NF-B，iNOS和胱天蛋白酶的表达变化，与伏立诺他相比，HO-1和NQO-1的mRNA水平显着增强。阴性对照组。此外，TUNEL分析还显示，与阴性对照组相比，伏立诺他治疗组的神经元细胞凋亡显着降低（p <0.01）。本研究得出结论，伏立诺他通过减少氧化应激和炎症反应的改变水平来保护TBI小鼠的神经元损伤。