Effects Of Intravenously Transplanted Bone Marrow Stromal Cells On Neurocyte Proliferation In The Ischemic Brain

Ischemic cerebrovascular diseases are familiar cases of nervous system.It is very diffcult that neuronal regeneration and self-repairs,so the organization repair and the function reconstruction after brain ischemia has vital clinical significance. In the past several years, it is usually hot spot of study that cellular transplant. Bone marrow stromal cells(BMSCs) are non-hematogenic stem cells from marrow.Studies find that BMSCs can be easily isolated and cultured,and can be used for transplantation without ethical consideration and immune excluded reaction,compared with the other stem cells. Based on those adventages, BMSCs are considered to be an attractive therapeutic tool for a lot of central nervous system diseases. Studies have approved that BMSCs can be induced into neural-like cells in vitro,and differentiate into neurons and astrocytes in vivo after transplantation .Significant recorvery of neurological function was found in rats treated with BMSCs. But its mechanism is not yet clear. However, the functional improvement observed with BMSCs treatment is unlikely to be attributable to BMSCs replacing the damaged neurons. The past studies demonstrated statistically significant increases in the cellular proliferation in SVZ,dentate gyrus, and boundary zone of the injured animals(without treatment). However, injury-induced cellular proliferation is insufficient to repair the neuronal damage, and external interventions are needed to treat ischemic cerebrovascular diseases.In the present study, cerebral ischemia-reperfusion injury model was established with four-vessel occlusion method. BMSCs were transplanted into rats through tail vein.To investigate the effects of intravenous administration of BMSCs on endogenous cellular proliferation after cerebral ischemia,and provide theoretical and experimental basis for BMSCs administration for treatment of ischemic cerebrovascular diseases. MethodsBone marrow stromal cells from adult rats were cultrated in vitro.After that the cells were labeled by Hoechst 33342,then were infused through tail vein into the adult rats 3 days,5days,7days after celebral artery occlusion. Morris water maze was used to explore the effects to learning and memory function of rats at 3 weeks after celebral artery occlusion. Fluorescence microscope was used to identify BMSCs in rats brain 4 weeks after celebral artery occlusion. Part and area of infarct were investigated by HE dyeing and immunofluorescence technique was used to investigate neurocyte proliferation in the ischemic brain.Results1. All of the test indices in Morris water maze were significantly different from those of control group at 3 treatment weeks.2. BMSCs survived and localized to the ipsilateral ischemic hemisphere.3. The pyramidal cells in the CA1 region of hippocampus in BMSCs transplanted group were significantly more than those of control group.4. The number of BrdU positive cells of BMSCs transplanted group was higher than those of control group. And the percentage of BrdUrd-positive cells expressing MAP-2 was significantly increased as compared with the control group.Conclusion1. BMSCs are able to survive and migrate to ischemic brain tissue through intravenous transplantion.2. Intravenous BMSCs administration are able to promote the learning and memory function of rats.3. Intravenous BMSCs administration are able to promote endogenous cellular proliferation and enhance the percentage of cells differentiate into neurons after cerebral ischemia.