Neuroprotection of Cytisine Against Cerebral Ischemia–Reperfusion Injury in Mice by Regulating NR2B-ERK/CREB Signal Pathway
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The aim of the study was to elucidate the therapeutic effects of Cytisine (CYT) on cerebral ischemia–reperfusion injury in mice. Male ICR mice were pretreated with reagents (drug), and then subjected to 2 h focal cerebral ischemia and 24 h reperfusion. Morphologically, the histopathological impairment were estimated by the TTC, HE and TUNEL staining. The expression of GluN2B-containing NMDA receptor, phosphorylation of extracellular regulated protein kinases, total ERK, phosphorylation of cAMP-response element binding protein and total CREB were determined by immunofluorescence and Western blot assay, respectively. The mRNA expression of NR2B, ERK and CREB were quantified by the real-time RT-PCR. CYT significantly diminished the infarct size and neuronal apoptosis. Additionally, it ameliorated histopathological lesion dramatically. CYT promoted the phosphorylation of ERK, CREB and their mRNA expression. In contrast, the expression of NR2B was suppressed in concomitant with the down-regulation of genes. The overall results thus far suggest that CYT confers the neuroprotection against cerebral I/R injury by regulating the NR2B-ERK/CREB signal pathway.
KeywordsCytisine Cerebral I/R injury P-CREB P-ERK NR2B
This work was supported by the Colleges and Universities of Science and Technology Research Projects (Grant No. NGY2013078).
Jian-Qiang Yu contributed to the conception of the study and approved the final version. Peng Zhao and Yue Liu significantly performed the experiments and drafted the manuscript preparation. Yin-Ju Hao and Yu-Xiang Li performed the data analyses. Nan Li and Jing Wang contributed reagents and materials. Yang Niu and Tao Sun revised the manuscript. We thank Drs. Lu-Ning Cui for his critical review and subsequent editing of this manuscript.
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Conflict of interest
The authors declare that they have no conflicts of interest.
- 41.Zhang W, Song JK, Yan R, Li L, Xiao ZY, Zhou WX, Wang ZZ, Xiao W, Du GH (2018) Diterpene ginkgolides protect against cerebral ischemia/reperfusion damage in rats by activating Nrf2 and CREB through PI3K/Akt signaling. Acta Pharmacol Sin. https://doi.org/10.1038/aps.2017.149 CrossRefPubMedGoogle Scholar