Cerebral ischemia and CNS transplantation: differential effects of grafted fetal rat striatal cells and human neurons derived from a clonal cell line

Cerebral ischemia and CNS transplantation: differential effects of grafted fetal rat striatal cells and human neurons derived from a clonal cell line
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DOI:
10.1097/00001756-199811160-00025
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发表时间:
1998-11-16
期刊:
影响因子:
1.7
通讯作者:
Sanberg, PR
Sanberg, PR
中科院分区:
医学4区
文献类型:
--
作者:
Borlongan, CV;Tajima, Y;Sanberg, PR

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近几十年来,中风死亡率有所下降,这促使人们需要为中风幸存者开发有效的康复疗法。使用相关动物模型复制真实人类脑缺血的行为和神经病理变化的重大进展促进了这一努力。由于大脑中动脉闭塞的啮齿动物模型模拟了临床脑缺血中出现的几种运动异常,因此我们利用该模型来研究脑卒中的治疗策略。本研究探讨了克隆胚胎癌细胞系提取的胎鼠纹状体细胞或人神经元进行神经移植以纠正脑缺血相关异常的潜在益处。我们在此报道,早在移植后1个月,神经移植就能改善缺血引起的行为功能障碍。值得注意的是,人类神经元移植诱导的恢复明显比胎鼠纹状体移植更强劲。因此,利用细胞系衍生的人类神经元作为替代的移植物来源,可以消除使用胎儿纹状体细胞进行移植治疗的后勤和伦理问题。人类神经元移植在治疗脑缺血相关的行为缺陷方面具有治疗潜力。神经病学报告9:3703-3709 (C) 1998 Lippincott Williams & Wilkins。
STROKE mortality has declined over recent decades, prompting a demand for the development of effective rehabilitative therapies for stroke survivors. This effort has been facilitated by significant progress in replicating the behavioral and neuropathological changes of authentic human cerebral ischemia using relevant animal models. Since the rodent model of middle cerebral artery occlusion mimics several motor abnormalities seen in clinical cerebral ischemia, we have utilized this model to investigate treatment strategies for stroke. The present study explored the potential benefits of neural transplantation of fetal rat striatal cells or human neurons derived from a clonal embryonal carcinoma cell line to correct the abnormalities associated with cerebral ischemia. We report here that ischemia-induced behavioral dysfunctions were ameliorated by the neural grafts as early as I month post-transplantation. Of note, transplantation of human neurons induced a significantly more robust recovery than fetal rat striatal grafts. Thus, the logistical and ethical concerns about the use of fetal striatal cells for transplantation therapy can be eliminated by exploiting cell line-derived human neurons as alternative graft sources. Transplantation of human neurons has a therapeutic potential for treatment of behavioral deficits associated with cerebral ischemia. NeuroReport 9: 3703-3709 (C) 1998 Lippincott Williams & Wilkins.