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.
Key Words
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Article info
Publication history
Published online: August 04, 2017
Accepted:
June 9,
2017
Received in revised form:
June 1,
2017
Received:
April 8,
2017
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.06.023
Copyright
© 2017 Published by Elsevier Inc. on behalf of National Stroke Association.
