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.

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: Zhonghai Yu, Min Cai, Xianting Li, Jingsi Zhang, Ting Wu, Feng Yang, Wen Zhu, Yijin Xiang, Wen Zhang, Jun Xiang, Dingfang Cai
• Journal: Brain research (Brain Res) Vol. 1685 Pg. 9-18 (04 15 2018) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 29425910 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Drugs, Chinese Herbal
• Neuroprotective Agents
• tongxinluo
• Mitogen-Activated Protein Kinase 3

Topics

• Animals
• Brain Ischemia (drug therapy, pathology)
• Disease Models, Animal
• Drugs, Chinese Herbal (pharmacology)
• MAP Kinase Signaling System (drug effects)
• Male
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Neuroprotective Agents (pharmacology)
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy, metabolism)
• Signal Transduction (drug effects)