Tissue plasminogen activator (tPA) is the gold standard treatment for
ischemic stroke in the time window of 3-4.5 hours after the onset of symptoms. However, tPA administration is associated with
inflammation and neurotoxic effects. Mesenchymal stem cells (MSC)-based
therapy is emerging as a promising therapeutic strategy to control different inflammatory conditions. This project was designed to examine the protective role of MSC administration alone or in combination with
royal jelly (RJ) five hours after
stroke onset. The mice model of
middle cerebral artery occlusion (MCAO) was established and put to six groups, including intact (healthy mice without
stroke), control (untreated
stroke), treated with mouse MSC (
mMSC), Sup (
conditioned medium), RJ and combination of
mMSC and RJ (
mMSC/RJ). Thereafter, behavioral functions, serum and brain (in both infarcted and non-infarcted tissues) levels of
interleukin (IL)-1β,
IL-4,
IL-10,
tumor necrosis factor-alpha (TNF-α) and
interferon-gamma (IFN-γ) the sizes of
brain infarction have been determined in the groups. Administration of
mMSC and
mMSC/RJ significantly improved the behavioral functions when compared to the controls.
mMSC, RJ and
mMSC/RJ significantly decreased the infarcted volumes. RJ and
mMSC/RJ, but not
mMSC, significantly decreased the
brain edema. The
infarction increased the serum levels of the
cytokines, except TNF-α, and treatment with
mMSC, Sup and RJ reduced serum levels of the pro-inflammatory
cytokines.
mMSC reduced IL-1β in the non-infarcted brain tissue. To conclude, data revealed that using
mMSC/RJ combination significantly reduced
stroke side effects, including
brain edema and serum levels of pro-inflammatory
cytokines, and suggested that combination
therapy of MSCs with RJ may be considered as an effective
stroke therapeutic strategy.