Remote liver ischaemic preconditioning protects rat brain against cerebral ischaemia-reperfusion injury by activation of an AKT-dependent pathway.

Remote limb ischaemic preconditioning has been shown to have beneficial effects in protecting brains against ischaemia-reperfusion (I/R) injury. However, little is known regarding the effect of remote liver ischaemic conditioning (RLIPC). We therefore investigated the effect of RLIPC on brain tissues suffering from I/R injury. Rats were randomly assigned to a sham group, a control group or a RLIPC group. Rats in all groups except for the sham group received middle cerebral artery occlusion (MCAO) for 1 h, followed by 48 h of reperfusion. For the RLIPC rats, four cycles of 5 min of liver ischaemia (portal vein, hepatic arterial and venous trunk occlusion) with 5 min intermittent reperfusion were carried out before cerebral ischaemia. Infarct volume was assessed after 48 h of reperfusion. Blood samples were taken for serum lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) tests. Morphological changes of cortical tissue and cellular apoptosis were determined. Right cortex tissues were taken for western blotting measurements. Our data demonstrate that RLIPC reduced cerebral I/R injury, decreased the volume of the MCAO-evoked infarct region, decreased serum levels of LDH and CK-MB, and reduced neurological deficits and apoptosis after I/R injury. Moreover, rats receiving RLIPC showed increased cortical AKT phosphorylation, but protein phosphorylation level was unchanged in the survivor activating factor enhancement (SAFE) signalling pathway. Accordingly, inhibition of AKT with wortmannin abolished the neuroprotective action of liver preconditioning. Our study showed for the first time that liver ischaemic preconditioning effectively protects brain against cerebral I/R injury by activating an AKT-dependent pathway.