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

Apoptosis is the main pathological aspect of neuronal injury after cerebral
ischemia–reperfusion (I/R) injury. However the detailedmolecular 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/phosphorelatedcaspase3
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.