Effects of novel brain prothctants on neuroregeneration falbwing brain ischemia

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Objects and Methods : Neuroregeneration and releasing neurotraphic factors have been considered as a mechanism for functional improvement after transplantation of bone marrow cells in experimental brain ischemia model. However protective effects of transplantation of bone marrow cells immediately after reperfusion have been rarely investigated. The present study examined, using rat transient focal ischemia model (90 min), different protective effects between intra-arterial and intravenous administration routs after transplantation of bone marrow mononuclear cells (BMMCs), which need no incubation period. Then, the present study sought to investigate whether an intravenous transplantation of bone marrow stromal cells (BMSCs), which require incubation period, has also protective effects in the same rat model, and whether a combined therapy with BMSC transplantation and immunosuppressant FK506 enhance such neuroprotection. Furthermore, distribution and differentiation of the transplanted … More BMSCs was also investigated, and longitudinal cellular dynamics of the transplanted cells using MRI.Results : Intra-arterial BMMC transplantation ameliorated infarct volume and improved functional scores, while intravenous BMMC transplantation had no such protective effects. The transplanted BMMCs were observed more frequently within the ischemic hemisphere in the intra-arterial administration group than the intravenous administration group. A combined therapy with intravenous BMSC transplantation and FK506 showed greater neuroprotection. The transplanted BMSCs were differentiated into neurons and astrocytes by one month after transplantation. MRI study revealed that the transplanted cells labeled with superparamagnetic iron oxide were observed on T2 weighted images, and that such cells were gradually decreased in number by one month after transplantation.Conclusions: The present study clearly showed that intra-arterial administration immediately after reperfusion potentiated the effective delivery of BMMCs to the brain compared to intravenous administration, and that FK506 combined with BMSC transplantation enhanced such neuroprotection, leading to a decrease in ischemic damage and good functional recovery in rat transient ischemia model. Efficient BMMC delivery to the brain and modification of transplantation circumstance may be important in clinical application of BMMC transplantation for the treatment of acute ischemic stroke. Less