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Topiramate Reverses Physiological and Behavioral Alterations by Postoperative Cognitive Dysfunction in Rat Model Through Inhibiting TNF Signaling Pathway.
NeuroMolecular Medicine ( IF 3.5 ) Pub Date : 2019-11-23 , DOI: 10.1007/s12017-019-08578-y Wenjie Su 1 , Min Xie 1 , Yao Li 1 , Xinran Gong 1 , Jiacen Li 1
NeuroMolecular Medicine ( IF 3.5 ) Pub Date : 2019-11-23 , DOI: 10.1007/s12017-019-08578-y Wenjie Su 1 , Min Xie 1 , Yao Li 1 , Xinran Gong 1 , Jiacen Li 1
Affiliation
This study aimed to investigate the effects of topiramate (TPM) on rats with postoperative cognitive dysfunction (POCD) and elucidate the underlying mechanism. Differentially expressed genes in propofol-treated group and vehicle control group were filtered out and visualized in heatmap based on R program. POCD rat models were established for validation of TPM’s anti-inflammatory action and Morris water maze (MWM) test was employed for assessment of spatial learning and memory ability of rats. Hematoxylin and eosin (HE) staining was applied to detect the neurodegeneration, and the apoptosis status was detected using TUNEL assay. In vitro, hippocampal microglia was treated with lipopolysaccharide or TPM to validate the TPM’s anti-inflammatory action. Cell apoptosis was detected with flow cytometry. Inflammatory factors were detected by enzyme-linked immunosorbent assay, and factor-associated suicide (Fas), Fas-associated protein with death domain (FADD) expression were detected by western blot. As results, TPM administration improved the spatial learning and memory ability in POCD rat by decreasing the expression levels of Fas, FADD, and inflammatory factors (tumor necrosis factor-α, TNF-α; interleukin-1β, IL-1β; interleukin-6, IL-6) in POCD rats. In addition, TPM down-regulated cell apoptotic rate to suppress POCD by decreasing the expression of Caspase8, Bcl2-associated X (Bax), and poly ADP-ribose polymerase-1 (PARP1) yet enhancing B-cell lymphoma-2 (Bcl-2) expression. Besides, inhibition of Fas enhanced TPM-induced down-regulation of apoptosis of neuronal cell in hippocampus tissues of POCD rats. Our results revealed that treatment of POCD rats with TPM could suppress neuronal apoptosis in the hippocampus tissues, and the neuroprotective effects of TPM may relate with the regulation of tumor necrosis factor (TNF) signaling pathway.
中文翻译:
托吡酯通过抑制TNF信号通路通过大鼠模型的术后认知功能障碍逆转生理和行为改变。
这项研究旨在调查托吡酯(TPM)对术后认知功能障碍(POCD)大鼠的影响,并阐明其潜在机制。筛选出异丙酚治疗组和媒介物对照组的差异表达基因,并基于R程序在热图中可视化。建立POCD大鼠模型以验证TPM的抗炎作用,并使用莫里斯水迷宫(MWM)测试评估大鼠的空间学习和记忆能力。用苏木精和曙红(HE)染色检测神经变性,并使用TUNEL法检测细胞凋亡状态。在体外,用脂多糖或TPM处理海马小胶质细胞,以验证TPM的抗炎作用。用流式细胞仪检测细胞凋亡。用酶联免疫吸附法检测炎症因子,用Western blot检测表达因子的自杀(Fas),表达Fas的死亡域蛋白(FADD)。结果,TPM给药通过降低Fas,FADD和炎症因子(肿瘤坏死因子-α,TNF-α,白介素-1β,IL-1β,白介素-6)的表达水平而改善了POCD大鼠的空间学习和记忆能力。 ,IL-6)在POCD大鼠中。此外,TPM通过降低Caspase8,与Bcl2相关的X(Bax)和多聚ADP-核糖聚合酶-1(PARP1)的表达而下调细胞凋亡率,从而抑制POCD,但增强B细胞淋巴瘤2(Bcl- 2)表达。此外,抑制Fas可以增强TPM诱导的POCD大鼠海马组织神经元细胞凋亡的下调。
更新日期:2019-11-23
中文翻译:
托吡酯通过抑制TNF信号通路通过大鼠模型的术后认知功能障碍逆转生理和行为改变。
这项研究旨在调查托吡酯(TPM)对术后认知功能障碍(POCD)大鼠的影响,并阐明其潜在机制。筛选出异丙酚治疗组和媒介物对照组的差异表达基因,并基于R程序在热图中可视化。建立POCD大鼠模型以验证TPM的抗炎作用,并使用莫里斯水迷宫(MWM)测试评估大鼠的空间学习和记忆能力。用苏木精和曙红(HE)染色检测神经变性,并使用TUNEL法检测细胞凋亡状态。在体外,用脂多糖或TPM处理海马小胶质细胞,以验证TPM的抗炎作用。用流式细胞仪检测细胞凋亡。用酶联免疫吸附法检测炎症因子,用Western blot检测表达因子的自杀(Fas),表达Fas的死亡域蛋白(FADD)。结果,TPM给药通过降低Fas,FADD和炎症因子(肿瘤坏死因子-α,TNF-α,白介素-1β,IL-1β,白介素-6)的表达水平而改善了POCD大鼠的空间学习和记忆能力。 ,IL-6)在POCD大鼠中。此外,TPM通过降低Caspase8,与Bcl2相关的X(Bax)和多聚ADP-核糖聚合酶-1(PARP1)的表达而下调细胞凋亡率,从而抑制POCD,但增强B细胞淋巴瘤2(Bcl- 2)表达。此外,抑制Fas可以增强TPM诱导的POCD大鼠海马组织神经元细胞凋亡的下调。