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Neurochemical Research

, Volume 38, Issue 11, pp 2305–2312 | Cite as

Neuroprotection by the Kappa-Opioid Receptor Agonist, BRL52537, is Mediated via Up-Regulating Phosphorylated Signal Transducer and Activator of Transcription-3 in Cerebral Ischemia/Reperfusion Injury in Rats

  • Shudong Fang
  • Hui Xu
  • Junrui Lu
  • Yesen Zhu
  • Hong Jiang
Original Paper

Abstract

The purpose of this study was to investigate whether the kappa-opioid receptor (KOR) agonist, BRL52537, has a neuroprotective effect against cerebral ischemia/reperfusion (I/R) injury in rats and further explore the underlying mechanisms. Adult male Sprague–Dawley rats were randomly assigned into sham (group A), I/R (group B), BRL52537 (KOR agonist) + I/R (group C), nor-BNI (nor-binaltorphimine, KOR antagonist) + I/R (group D), AG490 (STAT3 phosphorylation inhibitor) + I/R (group E), dimethyl sulfoxide (DMSO, vehicle of AG490) + I/R (group F), and BRL52537 + AG490 +I/R (group G) groups. Cerebral I/R injury was induced by 10 min exposure to global ischemia (4-VO). Histopathological changes and neuronal apoptosis were evaluated with H&E staining and the TUNEL assay, respectively. Expression levels of signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3 and caspase-3 were determined with western blot analysis. Our results showed that BRL52537 protects against I/R injury-induced brain damage and inhibits neuronal apoptosis to a significant extent. Additionally, BRL52537 promoted up-regulation of p-STAT3 and a marked decrease in caspase-3 expression. Based on the collective findings, we propose that the KOR agonist, BRL52537, protects against cerebral I/R injury via a mechanism involving STAT3 signaling.

Keywords

Cerebral ischemia Kappa-opioid receptor STAT3 Neruroprotection Reperfusion 

Notes

Acknowledgments

This work was supported by the Health Bureau of Shanghai, China (Grant No. 2008123).

Supplementary material

11064_2013_1139_MOESM1_ESM.pdf (457 kb)
Supplementary material 1 (PDF 456 kb)
11064_2013_1139_MOESM2_ESM.pdf (478 kb)
Supplementary material 2 (PDF 478 kb)

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Shudong Fang
    • 1
  • Hui Xu
    • 1
  • Junrui Lu
    • 1
  • Yesen Zhu
    • 1
  • Hong Jiang
    • 1
  1. 1.Department of AnaesthesiologyShanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina

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