Simvastatin combined with bone marrow stromal cells treatment activatesastrocytes to ameliorate neurological function after ischemic stroke in rats

Authors: YONGHUA ZHAO, QIAN ZHANG, ZHENWEI CHEN, NAIWEI LIU, CHIENCHIH KE, YOUHUA XU, WEIKANG WU

Abstract: Evidence indicates that reactive astrocytes play an important role in neurological functional amelioration after stroke. Bone marrow stromal cell (BMSC) transplantation-promoted astrocyte-derived neurotrophic factors' expressions resulted in decreasing the number of apoptotic neurons and improving neurogenesis and angiogenesis in the ischemic boundary zone. Recent studies found that simvastatin had neuroprotective activity in acute stroke. However, it is still ambiguous as to whether simvastatin combined with BMSCs can further activate astrocytes, which contribute to neurological functional recovery after ischemic stroke. In our present study, we established a middle cerebral artery occlusion model in rats and found that combination treatment of simvastatin and BMSCs could significantly increase neurological functional scores and induce activated astrocytes to enhance stromal cell-derived factor-1 α, vascular endothelial growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor expressions compared with BMSC alone (P < 0.05) by immunofluorescence staining on the 7th day after ischemia. Furthermore, western blot results showed that combination treatment could notably activate the AKT/mammalian target of rapamycin signaling pathway in oxygen-glucose deprivation-induced astrocytes. It was superior to BMSC treatment at the 5-min time point (P < 0.01). Therefore, we think that combination treatment should be a more effective therapy after stroke due to synergic functions of supplementary approaches.

Keywords: Astrocyte, bone marrow stromal cells, ischemic stroke, simvastatin

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