Iihoshi Satoshi, Honmou Osamu, Houkin Kiyohiro, Hashi Kazuo, Kocsis Jeffery D
Department of Neurosurgery, Sapporo Medical University School of Medicine, Sapporo, South-1st, West-16th, Chuo, Sapporo, Hokkaido 060-8543, Japan.
Brain Res. 2004 May 8;1007(1-2):1-9. doi: 10.1016/j.brainres.2003.09.084.
The primary objective of this study was to test the hypothesis that intravenous administration of autologous bone marrow cells could improve functional recovery after middle cerebral artery occlusion (MCAO) for 45 min in the rat and to determine specific time windows for efficacy. Mononuclear cells from autologous bone marrow were transfected with the LacZ reporter gene, and injected intravenously into rats at 3-72 h after induction of MCAO. Histological analysis of the ischemic lesion at 14 days after transplantation revealed reduced ischemic lesion volume. Lesion volume was 250+/-45 mm(3) (n=6) after MCAO without cell transplantation. Lesions were minimally detected by absence of 2,3,5-triphenyltetrazolium chloride (TTC) staining when bone marrow cells were infused 3 h after lesion induction. Lesions were clearly detected beginning with the 6-h postlesion group and became progressively larger at 12, 24 and 72 h (80+/-25, 140+/-18, and 180+/-22 mm(3), respectively; n=6 for each group). Transplanted LacZ(+) bone marrow cells accumulated extensively in and around the ischemic lesions, and immunohistochemistry suggests some neuronal and glial lineage differentiation. Behavioral testing (Morris water maze and Treadmill stress test) indicated greater functional recovery in the treated group. These findings suggest that early intervention with intravenous administration of autologous mononuclear cells from bone marrow can reduce lesion size in the MCAO model in the rat, and improve functional outcome.
静脉注射自体骨髓细胞可改善大鼠大脑中动脉闭塞（MCAO）45分钟后的功能恢复，并确定有效的特定时间窗。将来自自体骨髓的单核细胞用LacZ报告基因转染，并在MCAO诱导后3至72小时静脉注射到大鼠体内。移植后14天对缺血性病变进行组织学分析，结果显示缺血性病变体积减小。未进行细胞移植的MCAO大鼠，病变体积为250±45立方毫米（n = 6）。在病变诱导后3小时注入骨髓细胞时，通过2,3,5-三苯基四氮唑氯化物（TTC）染色未检测到明显病变。从病变后6小时组开始可清晰检测到病变，且在12、24和72小时时病变逐渐增大（分别为80±25、140±18和180±22立方毫米；每组n = 6）。移植的LacZ（+）骨髓细胞在缺血性病变及其周围大量聚集，免疫组织化学表明有一些神经元和神经胶质谱系分化。行为测试（莫里斯水迷宫和跑步机应激测试）表明治疗组的功能恢复更好。这些发现表明，早期通过静脉注射自体骨髓单核细胞进行干预可减小大鼠MCAO模型中的病变大小，并改善功能结局。
