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.
Keywords: PI3K/AKT; cerebral ischaemia/reperfusion; fibulin-5; neuroprotection; remote ischaemic postconditioning.
© 2017 John Wiley & Sons Australia, Ltd.