Exogenous and endogenous therapeutic effects of combination Sodium Ferulate and bone marrow stromal cells (BMSCs) treatment enhance neurogenesis after rat focal cerebral ischemia

Abstract

Combining bone marrow stromal cells (BMSCs) with pharmacological therapy is an attractive approach for neurological function recovery of stroke. Our previous reports demonstrated that Sodium Ferulate (SF) combined with BMSCs administration could facilitate BMSCs migration into the ischemic brain by up-regulation of stromal cell-derived factor-1 alpha (SDF-1α)/chemokine (CXC motif) receptor-4 axis after stroke. To further investigate whether combination treatment could enhance neurogenesis through exogenous and endogenous therapeutic effects, we established rat permanent middle cerebral artery occlusion (pMCAo) model and measured ischemic infarct size by magnetic resonance imaging (MRI) scanning in the present study. The results showed that combination treatment could dramatically reduce ischemic infarction size which may be attributed to the effects on decreasing brain edema and enhancing cerebral tissue perfusion at 3days after stroke. Immunofluorescence staining results indicated that combination treatment could not only promote expression of Glucose transporter 1(Glut1) and Neuron-specific class III beta-tubulin (Tuj1) in the periinfarct area, but also improve BMSCs expression of Glut1, GFAP and Tuj1. Moreover, it showed combination treatment could enhance the endogenous expression of Tuj-1 in ischemic boundary zone. These results perhaps associated with combination treatment up-regulating bone morphogenetic proteins (BMP)2/4 expressions and down-regulating Notch-1, Hes1 and Hes5 expressions as detected by Western Blot analysis. Our study firstly demonstrated in vivo that combination treatment could facilitate exogenous BMSCs differentiation into neural-and astrocytic-like cells, as well as enhance repair capacity of brain parenchymal cells by promoting glucose metabolism and endogenous neurogenesis after stroke. These results illustrate that administration of SF and BMSCs is a potential pathway of cell-based pharmacological treatment towards ischemic stroke.