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.

Potential Applications of Remote Limb Ischemic Conditioning for Chronic Cerebral Circulation Insufficiency

“…Additional studies have revealed that RLIC activates the PI3K-pAkt pathway to induce cardioprotective effects, significantly upregulating the Bcl-2/Bax ratio by increasing p-Akt levels and the p-Akt/Akt ratio (44). Similar findings have been observed in models of MCAO (45), indicating that this process may be uniform across different diseases. CCCI due to large artery stenosis leads to decreases in p-Akt levels and the Bcl-2/Bax ratio in the cytoplasm and synapses of hippocampal neurons, suggesting that inhibition of Akt phosphorylation decreases the Bcl-2/Bax ratio and levels of neuronal apoptosis.…”

Progress of Research on Exosomes in the Protection Against Ischemic Brain Injury

“…In this process, the expression of Bcl-2 inhibits the expression of Bax, thus alleviating nerve cell apoptosis and achieving a protective effect. The mechanism of this process may be related to the Janus kinase 2 (JAK2)/signal transducer and activator of transcription-3 (STAT3) pathway (Cheng et al, 2014) and the PI3K/Akt pathway (Zhang et al, 2017a); the latter pathway has been extensively studied, and the former requires further testing.…”

DHA Attenuates Hypoxia/Reoxygenation Injury by Activating SSeCKS in Human Cerebrovascular Pericytes

“…The main pathophysiological changes in cerebral ischemia are the destruction of the blood-brain barrier and the entrance of macromolecular substances into the brain tissue, leading to cerebral edema and even bleeding [23]. Thrombolytic therapy allows the occluded blood vessels to be recanalized, and ischemic brain tissue is restored in time, but this restoration is accompanied by complex pathophysiological changes that aggravate cell damage and cell death and then induce cerebral ischemia/reperfusion injury [24].…”