Transplantation of hNT neurons into the ischemic cortex: Cell survival and effect on sensorimotor behavior
Transplantation of hNT neurons into the ischemic cortex: Cell survival and effect on sensorimotor behavior
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DOI：
10.1002/jnr.20800
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发表时间：
2006-05-01
影响因子：
4.2
通讯作者：
Steinberg, GK
中科院分区：
文献类型：
--
作者：
Bliss, TM;Kelly, S;Steinberg, GK
细胞移植为中风提供了一种潜在的新治疗方法。使用在纹状体和额叶皮层产生缺血性损伤模型的动物研究表明，将hNT细胞（有丝分裂后未成熟神经元）移植到缺血性纹状体中会产生有益的效果。在这项研究中，我们研究了hNT细胞在中风模型中的作用，该模型中纹状体保持完整，损伤仅限于皮质。在脑远端中动脉闭塞（dMCAo）致脑卒中1周后，将hNT细胞移植到缺血皮质。移植后4周，即使在病变边缘，细胞也表现出强劲的存活。hNT细胞不迁移，但它们主要通过白质向周围薄壁组织延伸长神经突。在缺血动物中，神经突主要向病变方向延伸，而在未损伤动物中，神经突是双向延伸。当移植物和梗死灶之间有残存的皮层组织时，也可观察到神经突通过皮层向病变方向延伸。四项感觉-运动功能测试均出现长时间缺陷。hnt移植动物在一项运动测试中显示出功能恢复的显著改善，但相对于对照动物，其他三项测试没有影响。因此，尽管有明确的证据表明移植物存活和神经突延伸，但缺血后hNT细胞的功能益处并不能得到保证。功能益处可能取决于其他变量，如梗死位置、细胞是否成熟、所采用的行为测试、康复训练或尚未确定的因素。(c) 2006 Wiley-Liss, Inc。
Cell transplantation offers a potential new treatment for stroke. Animal studies using models that produce ischemic damage in both the striatum and the frontal cortex have shown beneficial effects when hNT cells (postmitotic immature neurons) were transplanted into the ischemic striatum. In this study, we investigated the effect of hNT cells in a model of stroke in which the striatum remains intact and damage is restricted to the cortex. hNT cells were transplanted into the ischemic cortex 1 week after stroke induced by distal middle cerebral artery occlusion (dMCAo). The cells exhibited robust survival at 4 weeks posttransplant even at the lesion border. hNT cells did not migrate, but they did extend long neurites into the surrounding parenchyma mainly through the white matter. Neurite extension was predominantly toward the lesion in ischemic animals but was bidirectional in uninjured animals. Extension of neurites through the cortex toward the lesion was also seen when there was some surviving cortical tissue between the graft and the infarct. Prolonged deficits were obtained in four tests of sensory-motor function. hNT-transplanted animals showed a significant improvement in functional recovery on one motor test, but there was no effect on the other three tests relative to control animals. Thus, despite clear evidence of graft survival and neurite extension, the functional benefit of hNT cells after ischemia is not guaranteed. Functional benefit could depend on other variables, such as infarct location, whether the cells mature, the behavioral tests employed, rehabilitation training, or as yet unidentified factors. (c) 2006 Wiley-Liss, Inc.