The role of p38MAPK signal pathway in the neuroprotective mechanism of limb postconditioning against rat cerebral ischemia/reperfusion injury

• Published in: Journal of the neurological sciences 2015-10, Vol.357 (1), p.270-275
• Main Authors: Li, Hao, Zhou, Suxian, Wu, Lan, Liu, Kaixiang, Zhang, Yuhu, Ma, Guixian, Wang, Lijuan
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; ATF2; Brain Ischemia - enzymology; Brain Ischemia - pathology; Cerebral ischemia/reperfusion; Hindlimb - blood supply; Imidazoles - pharmacology; Ischemic Postconditioning - methods; Limb ischemic postconditioning; Male; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Neurology; p38 MAPK; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Reperfusion Injury - enzymology; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Stroke
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2015.08.004

Abstract 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.