A therapeutic window for intravenous administration of autologous bone marrow after cerebral ischemia in adult rats
A therapeutic window for intravenous administration of autologous bone marrow after cerebral ischemia in adult rats
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DOI：
10.1016/j.brainres.2003.09.084
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发表时间：
2004-05-08
期刊：
影响因子：
2.9
通讯作者：
Kocsis, JD
中科院分区：
文献类型：
--
作者：
Iihoshi, S;Honmou, O;Kocsis, JD
本研究的主要目的是检验自体骨髓细胞静脉给药可改善大鼠大脑中动脉闭塞（MCAO）45 min后的功能恢复的假设，并确定有效性的具体时间窗。用LacZ报告基因转染自体骨髓来源的单核细胞，并在诱导MCAO后3-72 h静脉注射到大鼠体内。移植后14天的缺血性病变的组织学分析显示缺血性病变体积减少。MCAO后病变体积为250 +/- 45 mm（3）（n = 6），未进行细胞移植。损伤诱导后3 h注入骨髓细胞时，通过2，3，5-氯化三苯基四氮唑（TTC）染色的缺失检测到最低限度的损伤。从损伤后6小时组开始，病变清晰可见，并在12、24和72小时逐渐变大（分别为80 ± 25、140 ± 18和180 ± 22 mm;每组n=6）。移植的LacZ（+）骨髓细胞在缺血性病变内和周围广泛聚集，免疫组织化学显示一些神经元和神经胶质细胞系分化。行为测试（Morris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，静脉内给予来自骨髓的自体单核细胞的早期干预可以减小大鼠MCAO模型中的病变大小，并改善功能结果。(C)2004 Elsevier B. V.保留所有权利。
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. (C) 2004 Elsevier B.V. All rights reserved.