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Journal of Nuclear Medicine Vol. 47 No. 3 486-491
© 2006 by Society of Nuclear Medicine


Basic Science Investigation

Improved Expression of {gamma}-Aminobutyric Acid Receptor in Mice with Cerebral Infarct and Transplanted Bone Marrow Stromal Cells: An Autoradiographic and Histologic Analysis

Hideo Shichinohe, MD, PhD1, Satoshi Kuroda, MD, PhD1, Shunsuke Yano, MD, PhD1, Takako Ohnishi, MSc2, Hiroshi Tamagami, MSc2, Kazutoshi Hida, MD, PhD1 and Yoshinobu Iwasaki, MD, PhD1

1 Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan; and 2 Research and Development Division, Research Center, Nihon Medi-Physics Co. Ltd., Sodegaura, Japan

Correspondence: For correspondence or reprints contact: Satoshi Kuroda, MD, PhD, Department of Neurosurgery, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan. E-mail: skuroda{at}med.hokudai.ac.jp

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.

Key Words: bone marrow stromal cell • transplantation • cerebral infarct • iomazenil • autoradiography


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