Involvement of miR-27a/smurf1/ TNF-α and mitochondrial apoptotic pathway in apoptosis induced by cerebral ischemia–reperfusion injury in rats: The protective effect of chlorogenic acid

Abstract

AimsApoptosis may contribute to a considerable proportion of neuron death after acute cerebral ischemia, although the underlying mechanisms remain unknown. The purpose of this research is to investigate the effect of cerebral ischemia–reperfusion on miR-27a/smurf1 axis in rat cerebral cortex alone and in combination with chlorogenic acid. MethodsTo create a model of ischemic brain injury, nylon monofilament occlusion of the common carotid artery (CCAO) was used for 20 min. Chlorogenic acid (30 mg/kg) was given intraperitoneally (ip) 10 min before ischemia and 10 min before reperfusion. ResultsTUNEL staining of cerebral cortex neurons revealed an increase in the number of apoptotic neurons 24 h after reperfusion. At the molecular level, IR damage lowered bcl2 protein expression while simultaneously increasing bax levels and the bax/bcl2 ratio. Also, we observed higher miR-27a gene expression and higher TNF-α protein level as well as lower smurf1 protein expression after 24 h following CCAO. Treatment with chlorogenic acid significantly reduced the apoptotic damage and reversed molecular alterations in cerebral cortex neurons after IR. ConclusionOur findings indicate that miR-27a/smurf1/TNF-α axis may play a regulatory function in cerebral cortex cell death, providing a new target for novel therapeutic approaches during transit ischemic stroke. It was also shown that chlorogenic acid could restore these molecular changes, demonstrating that it is an effective agent against cerebral cortex apoptotic damage after acute IR injury.