原肌球蛋白受体激酶B
trk受体
神经营养因子
医学
海马结构
神经营养素
脑源性神经营养因子
奶油
神经科学
海马体
内科学
药理学
麻醉
冲程(发动机)
内分泌学
受体
生物
生物化学
基因
工程类
转录因子
机械工程
作者
Zhixiong Li,Huanyi Wang,Guangxu Xiao,Hong Du,Shuang He,Yi Feng,Boli Zhang,Yan Zhu
标识
DOI:10.1016/j.biopha.2021.111828
摘要
A mild ischemic stroke may cause both debilitating locomotor and cognitive decline, for which the mechanism is not fully understood, and no therapies are currently available. In this study, a nonfatal stroke model was constructed in mice by a modified middle cerebral artery occlusion (MCAO) procedure, allowing an extended recovery period up to 28 days. The extended MCAO model successfully mimicked phenotypes of a recovery phase post-stroke, including locomotor motor and cognitive deficiencies, which were effectively improved after Shuxuening injection (SXNI) treatment. Tissue slices staining showed that SXNI repaired brain injury and reduced neuronal apoptosis, especially in the hippocampus CA3 region. Transcriptomics sequencing study revealed 565 differentially expressed genes (DEGs) in the ischemic brain after SXNI treatment. Integrated network pharmacological analysis identified Neurotrophin/Trk Signaling was the most relevant pathway, which involves 15 key genes. Related DEGs were further validated by RT-PCR. Western-blot analysis showed that SXNI reversed the abnormal expression of BDNF, TrkB, Mek3 and Jnk1after stroke. ELISA found that SXNI increased brain level of p-Erk and Creb. At sub-brain level, the expression of BDNF and TrkB was decreased and GFAP was increased on the hippocampal CA3 region in the post-stroke recovery phase and this abnormality was improved by SXNI. In vitro experiments also found that oxygen glucose deprivation reduced the expression of BDNF and TrkB, which was reversed by SXNI. In summary, we conclude that SXNI facilitates the recovery of cognitive and locomotor dysfunction by modulating Neurotrophin/Trk Signaling in a mouse model for the recovery phase of post-ischemic stroke.
科研通智能强力驱动
Strongly Powered by AbleSci AI