Background： The functional improvement following bone marrow stromal cells （BMSCs） transplantation after stroke is directly related to the number of engrafted cells and neurogenesis in the injured brain. Here, we t...Background： The functional improvement following bone marrow stromal cells （BMSCs） transplantation after stroke is directly related to the number of engrafted cells and neurogenesis in the injured brain. Here, we tried to evaluate whether 3-methyl-1-phenyl-2-pyrazolin-5-one （MCI-186）, a free radical scavenger, might influence BMSCs migration to ischemic brain, which could promote neurogenesis and thereby enhance treatment effects after stroke. Methods： Rat transient middle cerebral artery occlusion （MCAO） model was established. Two separate MCAO groups were administered with either MC1-186 or phosphate-buffered saline （PBS） solution to evaluate the expression of stromal cell-derived factor-1 （SDF-1） in ischemic brain, and compared to that in sham group （n 5/group/time point[at 1,3, and 7 days after operation]）. The content ofchemokine receptor-4 （CXCR4, a main receptor of SDF-I） at 7 days after operation was also observed on cultured BMSCs. Another four MCAO groups were intravenously administered with either PBS, MCI-186, BMSCs （2 ×106）, or a combination of MCI-186 and BMSCs （n = 10/ group）. 5-bromo-2-deoxyuridine （BrdU） and Nestin double-immunofluorescence staining was performed to identity the engrafted BMSCs and neuronal differentiation. Adhesive-removal test and foot-fault evaluation were used to test the neurological outcome. Results： MC1-186 upregulated the expression ofSDF- 1 in ischemic brain and CXCR4 content in BMSCs was enhanced after hypoxic stimulation. When MCAO rats were treated with either MCI- 186, BMSCs, or a combination ofMCI- 186 and BMSCs, the neurologic function was obviously recovered as compared to PBS control group （P 〈 0.01 or 0.05, respectively）. Combination therapy represented a further restoration, increased the number of BMSCs and Nestin- cells in ischemic brain as compared with BMSCs monotherapy （P 〈 0.01）. The number ofengrafted-BMSCs was correlated with the density of neuronal cells in ischemic brain （r = 0.72, P 〈 0.01 ） and the improvement of foot-thult （r = 0.70, P 〈 0.0 t ）. Conclusion： MCI- 186 might promote BMSCs migration to the ischemic brain, amplify the neurogenesis, and improve the effects of cell therapy.展开更多
基金grants from National Natural Science Foundation of China，Natural Science Foundation of Jiangsu Province
文摘Background： The functional improvement following bone marrow stromal cells （BMSCs） transplantation after stroke is directly related to the number of engrafted cells and neurogenesis in the injured brain. Here, we tried to evaluate whether 3-methyl-1-phenyl-2-pyrazolin-5-one （MCI-186）, a free radical scavenger, might influence BMSCs migration to ischemic brain, which could promote neurogenesis and thereby enhance treatment effects after stroke. Methods： Rat transient middle cerebral artery occlusion （MCAO） model was established. Two separate MCAO groups were administered with either MC1-186 or phosphate-buffered saline （PBS） solution to evaluate the expression of stromal cell-derived factor-1 （SDF-1） in ischemic brain, and compared to that in sham group （n 5/group/time point[at 1,3, and 7 days after operation]）. The content ofchemokine receptor-4 （CXCR4, a main receptor of SDF-I） at 7 days after operation was also observed on cultured BMSCs. Another four MCAO groups were intravenously administered with either PBS, MCI-186, BMSCs （2 ×106）, or a combination of MCI-186 and BMSCs （n = 10/ group）. 5-bromo-2-deoxyuridine （BrdU） and Nestin double-immunofluorescence staining was performed to identity the engrafted BMSCs and neuronal differentiation. Adhesive-removal test and foot-fault evaluation were used to test the neurological outcome. Results： MC1-186 upregulated the expression ofSDF- 1 in ischemic brain and CXCR4 content in BMSCs was enhanced after hypoxic stimulation. When MCAO rats were treated with either MCI- 186, BMSCs, or a combination ofMCI- 186 and BMSCs, the neurologic function was obviously recovered as compared to PBS control group （P 〈 0.01 or 0.05, respectively）. Combination therapy represented a further restoration, increased the number of BMSCs and Nestin- cells in ischemic brain as compared with BMSCs monotherapy （P 〈 0.01）. The number ofengrafted-BMSCs was correlated with the density of neuronal cells in ischemic brain （r = 0.72, P 〈 0.01 ） and the improvement of foot-thult （r = 0.70, P 〈 0.0 t ）. Conclusion： MCI- 186 might promote BMSCs migration to the ischemic brain, amplify the neurogenesis, and improve the effects of cell therapy.
