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.

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.

• Authors: Shudong Fang, Hui Xu, Junrui Lu, Yesen Zhu, Hong Jiang
• Journal: Neurochemical research (Neurochem Res) Vol. 38 Issue 11 Pg. 2305-12 (Nov 2013) ISSN: 1573-6903 [Electronic] United States
• PMID: 23996400 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1-(3,4-dichlorophenyl)acetyl-2-(1-pyrrolidinyl)methylpiperidine
• Neuroprotective Agents
• Piperidines
• Pyrrolidines
• Receptors, Opioid, kappa
• STAT3 Transcription Factor
• Stat3 protein, rat
• Tyrphostins
• alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
• Caspase 3

Topics

• Animals
• Apoptosis (drug effects)
• Brain Ischemia (pathology)
• Caspase 3
• Male
• Neuroprotective Agents (pharmacology)
• Phosphorylation (drug effects)
• Piperidines (pharmacology)
• Pyrrolidines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Opioid, kappa (agonists)
• Reperfusion Injury (pathology, prevention & control)
• STAT3 Transcription Factor (biosynthesis)
• Tyrphostins (pharmacology)
• Up-Regulation