The therapeutic effect of the intravenous administration of bone marrow stromal cells for treating transient focal cerebral ischemia in rats

Objective To explore the feasibility and the mechanism of the intravenous administration of bone marrow stromal cells (BMSCs) for treating transient focal cerebral ischemia in rats. Methods After purified, proliferated, and marked with BrdU, the BMSCs were injected intravenously into rats 7 days after focal cerebral ischemia. Neurological Deficits Score (NDS) were evaluated before and following 1, 7, 14, 21and 28 days of middle cerebral artery occlusion (MCAO). Rats were euthanized at 28 days after MCAO. Brain sections were stained with hematoxylin and eosin (HE) for surveying the volume of infarction. Slides were stained by the terminal deoxynucleotidyl transferase -mediated dUTP-biotin nick-end labeling (TUNEL) method for apoptosis detection in situ. Double-staining immunohistochemistry of brain sections was used to identify cell-specific brain-derived neurotrophic factor (BDNF) expression in bromodeoxyuridine-reactive BMSCs. And microvascular density in ischemic boundary zone was also detected with immunochemical staining of factor. Results NDS in BMSCs-transplanted group at 21th day and 28th day of MCAO was significantly lower than that in control group (P0.05). Double immunostaining showed that grafted BMSCs had migrated to the ischemic boundary zone, survived and expressed BDNF. The number of apoptotic cells and the apoptotic rate in the BMSCs transplantation group decreased compared with that of control group (P 0.01). The microvascular density was higher in the ischemic boundary zone of BMSCs-transplanted group than that in the control group (P0.001). Conclusion The intravenous administration of BMSCs can promote the recovery of neurological function of rats with focal cerebral ischemia. The therapeutic effect of BMSCs on rats with focal cerebral ischemia may be derived from the reduction of apoptosis and the angiogenesis in the ischemic boundary zone.