title: Limb remote ischaemic postconditioning-induced elevation of fibulin-5 confers neuroprotection to rats with cerebral ischaemia/reperfusion injury: Activation of the AKT pathway.
abstract: Limb remote ischaemic postconditioning (RIPostC) is an effective and well-acknowledged treatment for brain ischaemia injury. The present study aimed to evaluate the role of fibulin-5 in the neuroprotection of RIPostC against cerebral ischaemia/reperfusion (I/R) injury in rats. The middle cerebral artery occlusion (MCAO) model was established in rats and then RIPostC was carried out by three cycles of 10 minutes occlusion/10 minutes release of the bilateral femoral artery at the beginning of the reperfusion. To downregulate the fibulin-5 level, fibulin-5 siRNA was injected into the lateral ventricle 24 hours before MCAO. According to our present study, RIPostC attenuated cerebral I/R injury by decreasing infarct volume, improving neurobehavioral score and suppressing blood brain barrier (BBB) leakage. Moreover, the mRNA and protein levels of fibulin-5 were upregulated by RIPostC at 24 hours and 72 hours after reperfusion. Downregulation of fibulin-5 attenuated the neuroprotection of RIPostC. Finally, the result showed that fibulin-5 was upregulated by RIPostC via activation of the PI3K/AKT pathway. Taken together, these results provide evidence that upregulation of fibulin-5 is involved in the beneficial effect of RIPostC against cerebral I/R injury.
authors.affiliation: Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Beijing Tsinghua Changgung Hospital, Beijing, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Guorong
authors.initials: G
authors.lastname: Bi
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005121:Extremities / Q000098:blood supply*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D057775:Ischemic Postconditioning; D008297:Male; D000066829:Neuroprotection; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction
chemical_list: D016326:Extracellular Matrix Proteins; C492372:Fbln5 protein, rat; D011994:Recombinant Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: PI3K/AKT; cerebral ischaemia/reperfusion; fibulin-5; neuroprotection; remote ischaemic postconditioning