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Effects of novel brain prothctants on neuroregeneration falbwing brain ischemia

新型脑保护剂对弱翼脑缺血神经再生的影响

基本信息

批准号：
18590958
负责人：
KATAYAMA Yasuo
金额：
$ 2.34万
依托单位：
Nippon Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

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

目的和方法：在实验性脑缺血模型中，神经再生和释放神经营养因子被认为是骨髓细胞移植后功能改善的机制之一。然而，在再灌注后立即移植骨髓细胞的保护作用很少被研究。本研究采用大鼠短暂性局灶性脑缺血模型(90min)，观察了无潜伏期的骨髓单个核细胞(BMMCs)移植后动脉和静脉给药途径的不同保护作用。然后，本研究试图研究需要潜伏期的骨髓基质细胞(BMSCs)静脉移植在相同的大鼠模型中是否也具有保护作用，以及BMSC移植和免疫抑制剂FK506联合治疗是否增强了这种神经保护作用。此外，移植的…的分布和分化结果：动脉内移植的BMMC可改善脑梗塞体积，改善功能评分，而静脉内移植的BMMC无此保护作用。动脉给药组比静脉给药组移植的骨髓单个核细胞在缺血侧更常见。静脉注射骨髓间充质干细胞移植和FK506联合治疗显示出更强的神经保护作用。移植后1个月，骨髓间充质干细胞分化为神经元和星形胶质细胞。MRI显示移植细胞在T2加权像上可见超顺磁性氧化铁标记的细胞，移植后1个月细胞数量逐渐减少。结论：与静脉注射相比，再灌注即刻动脉内注射可增强骨髓间充质干细胞向脑内的有效输送，FK506联合骨髓间充质干细胞移植可增强这种神经保护作用，使缺血损伤减轻，功能恢复良好。高效的BMMC向脑内转运和改善移植环境可能是BMMC移植治疗急性缺血性卒中的重要临床应用。较少

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Treatment using bone marrow stromal cells in rat brain ischemia model : neuroregeneration and neuroprotective effect

使用骨髓基质细胞治疗大鼠脑缺血模型：神经再生和神经保护作用

DOI：
发表时间：
2007
期刊：
影响因子：
0
作者：
Suda;S.;Shimazaki;K.;Ueda;M.;Kato;K.;Inaba;T.;Kamiya;N.;Nishiyama;Y.;Okubo;S.;Yokota;H.;Oguro;K.;Watanabe;H.;Katayama;Y
通讯作者：
Y

Different effects of brain protection between administration routes of bone marrow mononuclear cells in rat brain ischemia model

不同给药途径骨髓单个核细胞对大鼠脑缺血模型脑保护作用的差异