MiR-23b/TAB3/NF-κB/p53 axis is involved in hippocampus injury induced by cerebral ischemia-reperfusion in rats: The protective effect of chlorogenic acid.

Abstract

Apoptosis is the main pathological aspect of neuronal injury after cerebral ischemia-reperfusion (I/R) injury. However the detailed molecular mediators are still under debate. The aim of this study is to explore the effect of cerebral I/R on miR-23a/TGF-β-activated kinase 1 binding protein 3 (TAB3)/nuclear factor kappa B (NF-κB)/p53 axis in rat hippocampus alone and in combination with chlorogenic acid (CGA). Common carotid artery occlusion (CCAO) was performed by nylon monofilament for 20 min to establish a model of ischemic brain injury. CGA (30 mg/kg) was administered intraperitoneally (ip), 10min prior to ischemia and 10min before reperfusion. Examination of hippocampus neurons by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining showed that the number of apoptotic neurons was elevated at 24 h after reperfusion. At the molecular levels, I/R injury resulted in an increased protein expression of p53 with a concomitant upregulation of cleaved-caspase3/phosphorelated-caspase3 ratio and cytochrome c level. Further miR-23b gene expression was significantly downregulated after 24 h of reperfusion. Also, we observed increased TAB3 and NF-κB protein expressions after 24 h following CCAO. Treatment with CGA significantly reduced the apoptotic damage and also reversed miR-23b gene expression, TAB3 and NF-κB protein expressions in hippocampus neurons in I/R rats. In conclusion our data suggest that miR-23b/TAB3/NF-κB/p53 axis could play a regulatory role in hippocampus cell death, which provide a new target for novel therapeutic interventions during transit ischemic stroke. It also demonstrated that CGA could reverse these molecular alterations indicating an effective component against hippocampus apoptotic insult following acute I/R injury.