Improved expression of gamma-aminobutyric acid receptor in mice with cerebral infarct and transplanted bone marrow stromal cells: an autoradiographic and histologic analysis.
Improved expression of gamma-aminobutyric acid receptor in mice with cerebral infarct and transplanted bone marrow stromal cells: an autoradiographic and histologic analysis.
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发表时间：
2006-03
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通讯作者：
H. Shichinohe;S. Kuroda;S. Yano;T. Ohnishi;H. Tamagami;K. Hida;Y. Iwasaki
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作者：
H. Shichinohe;S. Kuroda;S. Yano;T. Ohnishi;H. Tamagami;K. Hida;Y. Iwasaki
最近的研究表明，骨髓基质细胞（BMSC）移植到中枢神经系统疾病的动物模型中，具有改善神经功能的潜力。然而，移植的BMSC如何恢复失去的神经功能尚不清楚。因此，在本研究中，我们的目的是阐明是否BMSC表达神经元特异性γ-氨基丁酸（GABA）受体时，移植到脑梗死已受到大脑。方法从绿色荧光蛋白转基因小鼠中分离骨髓间充质干细胞，进行原代培养。使小鼠经受永久性大脑中动脉闭塞。损伤后7天将BMSC或载体移植到同侧纹状体中。采用放射自显影和荧光免疫组织化学方法，我们评估了125 I-iomazenil的结合和GABA受体蛋白在脑梗死和周围移植后4周的表达。结果BMSC移植动物梗死周围新皮质中125 I-碘马西尼的结合显著高于载体移植动物。同样，GABAA受体阳性细胞的数量在BMSC移植的动物中梗死周围新皮质中显著高于载体移植的动物。移植的BMSC的某个亚群表达神经元特异性标志物、微管相关蛋白2和梗死周围区域中GABAA受体特异性标志物蛋白。结论BMSC可能通过向梗死周围迁移并获得神经元特异性受体功能而促进神经组织再生。
UNLABELLED Recent studies have indicated that bone marrow stromal cells (BMSC) have the potential to improve neurologic function when transplanted into animal models of central nervous system disorders. However, how the transplanted BMSC restore the lost neurologic function is not clear. In the present study, therefore, we aimed to elucidate whether BMSC express the neuron-specific gamma-aminobutyric acid (GABA) receptor when transplanted into brain that has been subjected to cerebral infarction. METHODS The BMSC were harvested from green fluorescent protein-transgenic mice and were cultured. The mice were subjected to permanent middle cerebral artery occlusion. The BMSC or vehicle was transplanted into the ipsilateral striatum 7 d after the insult. Using autoradiography and fluorescence immunohistochemistry, we evaluated the binding of 125I-iomazenil and the expression of GABA receptor protein in and around the cerebral infarct 4 wk after transplantation. RESULTS Binding of 125I-iomazenil was significantly higher in the periinfarct neocortex in the BMSC-transplanted animals than in the vehicle-transplanted animals. Likewise, the number of the GABAA receptor-positive cells was significantly higher in the periinfarct neocortex in the BMSC-transplanted animals than in the vehicle-transplanted animals. A certain subpopulation of the transplanted BMSC expressed a neuron-specific marker, microtubule-associated protein 2, and the marker protein specific for GABAA receptor in the periinfarct area. CONCLUSION These findings suggest that BMSC may contribute to neural tissue regeneration through migrating toward the periinfarct area and acquiring the neuron-specific receptor function.