Isosteviol Sodium Protects Against Permanent Cerebral Ischemia Injury in Mice via Inhibition of NF-κB-Mediated Inflammatory and Apoptotic Responses

Background: Isosteviol sodium (STVNa) has been reported to have neuroprotective effects against ischemia/reperfusion (I/R) injury in rats. Furthermore, recanalization treatments, including thrombolytic therapy, have several limitations. Excessive inflammation and apoptosis contribute to the pathogenesis of ischemic brain damage. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) is critical to these processes and is associated with cerebral ischemia. Therefore, we studied the potential therapeutic effects and mechanisms of STVNa on permanent cerebral ischemia in mice. Methods: Permanent middle cerebral artery occlusion (pMCAO) was established via the suture method, followed by intravenous STVNa (7.5, 15, 30, 45, and 60 mg/kg). Neurobehavioral deficits, infarct volume, and histology were examined 24 hours after cerebral ischemia. In addition, the messenger RNA (mRNA) expression of NF-kappa B-related genes was detected using real-time quantitative polymerase chain reaction (qPCR). Results: STVNa (30 mg/kg) had significant neuroprotective effects 24 hours after pMCAO, including the reduction of the infarct volume and the improvement of the neurological severity score. Immunohistochemistry demonstrated that STVNa significantly increased the number of restored neurons and decreased the number of astrocytes. qPCR also demonstrated that the mRNA expression of inhibitor of nuclear factor kappa-B kinase-alpha, inhibitor of nuclear factor kappa-B kinase-beta, NF-kappa B, inhibitor of NF-kappa B-alpha, tumor necrosis factor-alpha, interleukin-1 beta, Bcl2-associated X protein, and caspase-3 were significantly downregulated, whereas B-cell CLL/lymphoma 2 mRNA was upregulated with STVNa treatment compared with vehicle. Conclusions: These findings demonstrate a neuroprotective role of STVNa during cerebral ischemia, which may result from interactions with the NF-kappa B signaling pathway and the associated inflammatory and apoptotic responses. (C) 2017 Published by Elsevier Inc.