The role of p38MAPK signal pathway in the neuroprotective mechanism of limb postconditioning against rat cerebral ischemia/reperfusion injury.
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 24h 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.
Southern Medical University, Guangzhou, Guangdong Province, China; Department of Neurology, Guangdong Neuroscience Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, China.
Hao
H
Li
Department of Endocrinology, Affiliated Hospital of Guilin Medical University, Guilin, China.
Suxian
S
Zhou
Department of Neurology, Affiliated Hospital of Guilin Medical University, Guilin, China.
Lan
L
Wu
Department of Neurology, Affiliated Hospital of Guilin Medical University, Guilin, China.
Kaixiang
K
Liu
Department of Neurology, Guangdong Neuroscience Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, China.
Yuhu
Y
Zhang
Department of Neurology, Guangdong Neuroscience Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, China.
Guixian
G
Ma
Department of Neurology, Guangdong Neuroscience Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, China. Electronic address: wljgd68@163.com.
Lijuan
L
Wang
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000473:pathology; D006614:Hindlimb / Q000098:blood supply*; D007093:Imidazoles / Q000494:pharmacology; D057775:Ischemic Postconditioning / Q000379:methods*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*
D007093:Imidazoles; D011725:Pyridines; C093642:SB 203580
ATF2; Apoptosis; Cerebral ischemia/reperfusion; Limb ischemic postconditioning; Stroke; p38 MAPK