Molecular mechanism underlying neuroprotective effect of central administration of recombinant resistin in mouse model of stroke

Sedigheh Behrouzifar,1,* Abedin vakili,2 Mehdi barati,3

1. Research Center and Department of Physiology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
2. Research Center and Department of Physiology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
3. Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran

Abstract


Introduction

Our recent research showed that resistin has a neuroprotective effect against stroke-induced injury through suppressing apoptosis and oxidative stress. however, the molecular mechanism of neuroprotection of resistin is unclear. this work was designed to examine the effect of mouse recombinant resistin on mrna expression of tumor necrosis factor-α (tnf-α), interleukin-1β (il-1β), interleukin-10 (il-10), transforming growth factor-β1 (tgf- β1), and heat shock protein-70 (hsp-70) in a mouse model of stroke.

Methods

Transient focal cerebral ischemia was induced by the middle cerebral artery occlusion (mcao) in mice. tnf-α, il-1β, il-10, tgf-β1 and hsp-70 mrna were detected at sham (0 h), 3 h, 6 h, 12 h and 24 h after mcao using real-time qrt-pcr method. moreover, animals were treated with resistin at the dose of 400 ng/mouse at the commencement of mcao, and mrna expression of the cytokines and hsp-70 was measured 24 h after mcao.

Results

Tumor necrosis factor-α and il-1β mrna expression markedly increased at 12-h time point and then returned to the basal level at 24 h after mcao; but hsp-70 mrna expression increased at 24-h time point. furthermore, resistin (400 ng/mouse) significantly increased tgf-β1 and il-10 and decreased hsp-70 gene expression at 24 h after mcao.

Conclusion

Our findings revealed that a molecular mechanism of attenuating ischemic damage by resistin administration probably is increased mrna expression of anti-inflammatory cytokines. however, applying resistin in the clinical settings for the treatment of stroke deserves further researches in the future.

Keywords

Resistin, cerebral ischemia, gene expression, cytokines, heat shock protein-70