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Neuroprotective effects of Tongxinluo on focal cerebral ischemia and reperfusion injury in rats associated with the activation of the MEK1/2/ERK1/2/p90RSK signaling pathway.
Brain Res. 2018 04 15; 1685:9-18.BR

Abstract

Ischemic stroke brings a huge family and social burden. Although the reperfusion of ischemic cerebral tissue is the most important way to rescue ischemic stroke, ischemia-reperfusion (I/R) injury further results in brain damage and even lead to death. Recent studies demonstrated that Tongxinluo (TXL) helps to protect the brain against focal cerebral I/R injury in rats by reducing neuronal apoptosis, and the MEK1/2/ERK1/2/90 ribosomal S6 kinase (p90RSK) pathway may be involved in this protective effect. Therefore, our present research was designed to identify the potential mechanisms involved. Adult male Sprague-Dawley rats (n = 108) were randomly divided into 4 groups: sham, cerebral ischemia and reperfusion (I/R), I/R plus TXL (TXL), and TXL plus U0126, a highly selective inhibitor of MEK 1 and MEK 2 (TXL + U0126). Brain edema was measured by T2-weighted magnetic resonance imaging (MRI). Pathological destruction of the blood brain barrier (BBB) ultrastructure was assessed by transmission electron microscopy, and proteins involved in the MEK1/2/ERK1/2/p90RSK pathway were detected by immunofluorescence and Western blotting. Our results indicated that TXL significantly improved neurological function, reduced brain edema, ameliorated the destruction of the BBB ultrastructure and markedly reduced neuronal injury. However, these benefits were diminished when the MEK1/2/ERK1/2/p90RSK pathway was inhibited by U0126. We also found that TXL upregulated the expression levels of p-MEK1/2, p-ERK1/2, p-p90RSK and p-bad, which were all significantly reversed by U0126. Collectively, our data demonstrate that TXL provides neuroprotection against cerebral I/R injury and neuronal injury, and that these effects are mediated, in part, by activation of the MEK1/2/ERK1/2/p90RSK pathway.

Authors+Show Affiliations

Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai, China.Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai, China.Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai, China.Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai, China.Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai, China.Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai, China.Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai, China.Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai, China.Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai, China.Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai, China. Electronic address: xiang.jun@mail.zs-hospital.sh.cn.Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai, China. Electronic address: dingfangcai@126.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29425910

Citation

Yu, Zhonghai, et al. "Neuroprotective Effects of Tongxinluo On Focal Cerebral Ischemia and Reperfusion Injury in Rats Associated With the Activation of the MEK1/2/ERK1/2/p90RSK Signaling Pathway." Brain Research, vol. 1685, 2018, pp. 9-18.
Yu Z, Cai M, Li X, et al. Neuroprotective effects of Tongxinluo on focal cerebral ischemia and reperfusion injury in rats associated with the activation of the MEK1/2/ERK1/2/p90RSK signaling pathway. Brain Res. 2018;1685:9-18.
Yu, Z., Cai, M., Li, X., Zhang, J., Wu, T., Yang, F., Zhu, W., Xiang, Y., Zhang, W., Xiang, J., & Cai, D. (2018). Neuroprotective effects of Tongxinluo on focal cerebral ischemia and reperfusion injury in rats associated with the activation of the MEK1/2/ERK1/2/p90RSK signaling pathway. Brain Research, 1685, 9-18. https://doi.org/10.1016/j.brainres.2018.01.036
Yu Z, et al. Neuroprotective Effects of Tongxinluo On Focal Cerebral Ischemia and Reperfusion Injury in Rats Associated With the Activation of the MEK1/2/ERK1/2/p90RSK Signaling Pathway. Brain Res. 2018 04 15;1685:9-18. PubMed PMID: 29425910.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective effects of Tongxinluo on focal cerebral ischemia and reperfusion injury in rats associated with the activation of the MEK1/2/ERK1/2/p90RSK signaling pathway. AU - Yu,Zhonghai, AU - Cai,Min, AU - Li,Xianting, AU - Zhang,Jingsi, AU - Wu,Ting, AU - Yang,Feng, AU - Zhu,Wen, AU - Xiang,Yijin, AU - Zhang,Wen, AU - Xiang,Jun, AU - Cai,Dingfang, Y1 - 2018/02/07/ PY - 2017/10/28/received PY - 2018/01/29/revised PY - 2018/01/30/accepted PY - 2018/2/10/pubmed PY - 2019/4/20/medline PY - 2018/2/10/entrez KW - Bad protein KW - Cerebral ischemia and reperfusion injury KW - MEK12ERK12p90RSK pathway KW - Neuroprotection KW - Tongxinluo SP - 9 EP - 18 JF - Brain research JO - Brain Res. VL - 1685 N2 - Ischemic stroke brings a huge family and social burden. Although the reperfusion of ischemic cerebral tissue is the most important way to rescue ischemic stroke, ischemia-reperfusion (I/R) injury further results in brain damage and even lead to death. Recent studies demonstrated that Tongxinluo (TXL) helps to protect the brain against focal cerebral I/R injury in rats by reducing neuronal apoptosis, and the MEK1/2/ERK1/2/90 ribosomal S6 kinase (p90RSK) pathway may be involved in this protective effect. Therefore, our present research was designed to identify the potential mechanisms involved. Adult male Sprague-Dawley rats (n = 108) were randomly divided into 4 groups: sham, cerebral ischemia and reperfusion (I/R), I/R plus TXL (TXL), and TXL plus U0126, a highly selective inhibitor of MEK 1 and MEK 2 (TXL + U0126). Brain edema was measured by T2-weighted magnetic resonance imaging (MRI). Pathological destruction of the blood brain barrier (BBB) ultrastructure was assessed by transmission electron microscopy, and proteins involved in the MEK1/2/ERK1/2/p90RSK pathway were detected by immunofluorescence and Western blotting. Our results indicated that TXL significantly improved neurological function, reduced brain edema, ameliorated the destruction of the BBB ultrastructure and markedly reduced neuronal injury. However, these benefits were diminished when the MEK1/2/ERK1/2/p90RSK pathway was inhibited by U0126. We also found that TXL upregulated the expression levels of p-MEK1/2, p-ERK1/2, p-p90RSK and p-bad, which were all significantly reversed by U0126. Collectively, our data demonstrate that TXL provides neuroprotection against cerebral I/R injury and neuronal injury, and that these effects are mediated, in part, by activation of the MEK1/2/ERK1/2/p90RSK pathway. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/29425910/Neuroprotective_effects_of_Tongxinluo_on_focal_cerebral_ischemia_and_reperfusion_injury_in_rats_associated_with_the_activation_of_the_MEK1/2/ERK1/2/p90RSK_signaling_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(18)30056-8 DB - PRIME DP - Unbound Medicine ER -