- •Limb ischemia postconditioning (LPostC) has showed the neuroprotective effects in cerebral ischemia/reperfusion rats.
- •LPostC has decreased the neuronal apoptosis in ischemia/reperfusion.
- •LPostC or SB203580 (p38 MAPK inhibitor) has inhibited the activation of p38 and ATF-2 in cerebral ischemia/reperfusion rats.
- •The neuroprotective effects of LPostC may be related to its inhibiting p38-ATF-2 pathway.
It has been reported that remote ischemic postconditioning was able to protect from a harmful ischemia occurring in brain. In the present study, we investigated the role of p38 MAPK signal pathway in the process of neuroprotection and anti-apoptosis following remote limb ischemic postconditioning on rat focal cerebral ischemia/reperfusion (I/R) model. Male Sprague–Dawley rats were divided randomly into four groups: the sham-operated group, I/R group, limb ischemic postconditioning (LPostC) group, and LPostC + SB203580 (p38 MAPK inhibitor) group. Focal ischemia was induced by transient middle cerebral artery occlusion. Limb ischemic postconditioning was implemented by brief cycles of femoral artery occlusion. At 24 h after modeling, we analyzed the neurological deficit score, assessed the cerebral tissue morphology by H-E staining, and evaluated neuronal apoptosis by TUNEL staining. The protein expression levels of p-p38 or p-ATF2 (phospho-activating transcription factor 2) in the penumbra region were detected by western blotting or immunohistochemical staining. Our findings revealed that LPostC relieved cerebral ischemia/reperfusion injury by decreasing neurological score, improving neuronal morphological changes in the ischemic penumbra area, and reducing neuronal apoptosis. In addition, LPostC or LPostC + SB203580 attenuated the increase in p-p38 and p-ATF2 levels in ischemia/reperfusion brain tissue. These results indicate that the protective effects of LPostC against cerebral I/R injury may be related to the attenuation of neuronal apoptosis and the suppression of p38 MAPK-ATF2 pathway.
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Published online: August 05, 2015
Accepted: August 4, 2015
Received in revised form: July 26, 2015
Received: June 15, 2015
© 2015 Elsevier B.V. Published by Elsevier Inc. All rights reserved.