The protective effect and mechanism of ISO-1 in cerebral ischemia/reperfusion injury

Abstract

Abstract Macrophage migration inhibitory factor (MIF) is an immune mediator associated with inflammation, which is upregulated after ischemia in brain tissue. ISO-1 is a potent inhibitor of MIF tautomerase and can protect against neurons by reducing the permeability of blood brain barrier (BBB). In this study, we investigated the role of ISO-1 in ischemia / reperfusion injury in the brain by establishing a model of middle cerebral artery occlusion / reperfusion in rats. Rats were randomized into four groups: the sham operation group, the ISO-1group, the cerebral I/R group, and the ISO-1 + I/R group. We evaluated the degree of neurological deficit in each group and measured the volume of cerebral infarction. We detected the expression of MIF in the core necrotic area and penumbra. We detected the expression of apoptosis-related proteins, apoptosis-inducing factor (AIF), endonuclease G (EndoG) and cytochrome c oxidase-IV (COX-IV) in the ischemic penumbra region. The results showed that the expression of MIF in the ischemic penumbra area, while ISO-1 injection was able to alleviate nerve function defect and reduce infarction area. In cerebral ischemic penumbra region, ISO-1 could reduc the expression of Bax and Caspase3, and inhibit the displacement of AIF and EndoG to the nucleus simultaneously. Besides, ISO-1 also exhibited the ability to reduce apotosis. In summary, ISO-1 may inhibit neuronal apoptosis through the endogenous mitochondrial pathway and reduce the injury of brain I/R after ischemic stroke.