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-κB) 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-κB-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-α, inhibitor of nuclear factor kappa-B kinase-β, NF-κB, inhibitor of NF-κB-α, tumor necrosis factor-α, 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-κB signaling pathway and the associated inflammatory and apoptotic responses.
['Zhang|Hao|H|', 'Sun|Xiaoou|X|', 'Xie|Yanxiang|Y|', 'Zan|Jie|J|', 'Tan|Wen|W|']
D000818:Animals D017209:Apoptosis D001930:Brain Injuries D002545:Brain Ischemia D053148:Caspase 3 D002560:Cerebrovascular Circulation D016207:Cytokines D004195:Disease Models, Animal D045786:Diterpenes, Kaurane D015971:Gene Expression Regulation, Enzymologic D005904:Glial Fibrillary Acidic Protein D007249:Inflammation D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D016328:NF-kappa B D009460:Neurologic Examination D018696:Neuroprotective Agents
Permanent cerebral ischemia inflammatory STVNa apoptosis NF-κB