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), 10 min prior to ischemia and 10 min 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.