Early transplantation of an encapsulated glial cell line-derived neurotrophic factor-producing cell demonstrating strong neuroprotective effects in a rat model of Parkinson disease.
Early transplantation of an encapsulated glial cell line-derived neurotrophic factor-producing cell demonstrating strong neuroprotective effects in a rat model of Parkinson disease.
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DOI：
10.3171/jns.2005.102.1.0080
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发表时间：
2005
影响因子：
4.1
通讯作者：
T. Yasuhara;T. Shingo;K. Muraoka;Kazuki Kobayashi;Akira Takeuchi;A. Yano;Yuan Wenji;M. Kameda;T. Matsui;Y. Miyoshi;I. Date
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文献类型：
--
作者：
T. Yasuhara;T. Shingo;K. Muraoka;Kazuki Kobayashi;Akira Takeuchi;A. Yano;Yuan Wenji;M. Kameda;T. Matsui;Y. Miyoshi;I. Date
对象 胶质细胞源性神经营养因子 (GDNF) 已被证明对多巴胺能神经元具有神经保护作用。作者在体外和体内研究了 GDNF 对 6-羟基多巴胺 (6-OHDA) 处理的多巴胺能神经元的影响。方法 首先，作者检查了在添加 6-OHDA 之前 24 小时、同时或添加 2 或 4 小时后向细胞施用 1、10 或 100 ng/ml GDNF 对多巴胺能神经元的影响。在 E14 鼠腹侧中脑神经元的原代培养物中，早期使用较高剂量的 GDNF 治疗比后期治疗更好地抑制 6-OHDA 诱导的多巴胺能神经元损失。接下来，作者检查了在早期时间点连续输注 GDNF 是否会在帕金森病 (PD) 大鼠模型中表现出更大的神经保护作用。他们建立了一种人类 GDNF 分泌细胞系，称为 BHK-GDNF，并将细胞封装到中空纤维中。 1周前将包膜细胞单侧植入成年大鼠纹状体；同时；或者在给予6-OHDA后1、2或4周诱导同一纹状体的损伤。随着 BHK-GDNF 胶囊的早期移植，动物表现出的安非他明诱导的旋转次数显着减少。较早植入 BHK-GDNF 胶囊的大鼠在黑质致密部显示出更多的酪氨酸羟化酶阳性神经元，并且纹状体中有胶质细胞增殖的趋势。结论 这些神经保护作用可能与神经胶质细胞增殖和 GDNF 受体 α1 的信号传导有关。这项研究的结果支持了这种移植技术在帕金森病治疗中的作用。
OBJECT Glial cell line-derived neurotrophic factor (GDNF) has been shown to confer neuroprotective effects on dopaminergic neurons. The authors investigated the effects of GDNF on 6-hydroxydopamine (6-OHDA)-treated dopaminergic neurons in vitro and in vivo. METHODS First, the authors examined how 1, 10, or 100 ng/ml of GDNF, administered to cells 24 hours before, simultaneously with, or 2 or 4 hours after 6-OHDA was added, affected dopaminergic neurons. In a primary culture of E14 murine ventral mesencephalic neurons, earlier treatment with the higher dosage of GDNF suppressed 6-OHDA-induced loss of dopaminergic neurons better than later treatment. Next, the authors examined whether continuous infusion of GDNF at earlier time points would demonstrate a greater neuroprotective effect in a rat model of Parkinson disease (PD). They established a human GDNF-secreting cell line, called BHK-GDNF, and encapsulated the cells into hollow fibers. The encapsulated cells were unilaterally implanted into the striatum of adult rats 1 week before; simultaneously with; or 1, 2, or 4 weeks after 6-OHDA was given to induce lesions of the same striatum. With the earlier transplantation of a BHK-GDNF capsule, there was a significant reduction in the number of amphetamine-induced rotations displayed by the animals. Rats that had received earlier implantation of BHK-GDNF capsules displayed more tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta and a tendency for glial proliferation in the striatum. CONCLUSIONS These neuroprotective effects may be related to glial proliferation and signaling via the GDNF receptor alpha1. The results of this study support a role for this grafting technique in the treatment of PD.