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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.

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.

journal_name

Brain Res

journal_title

Brain research

authors

Yu Z,Cai M,Li X,Zhang J,Wu T,Yang F,Zhu W,Xiang Y,Zhang W,Xiang J,Cai D

doi

10.1016/j.brainres.2018.01.036

subject

Has Abstract

pub_date

2018-04-15 00:00:00

pages

9-18

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(18)30056-8

journal_volume

1685

pub_type

杂志文章

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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.