Progressive and extensive dopaminergic degeneration induced by convection-enhanced delivery of 6-hydroxydopamine into the rat striatum: a novel rodent model of Parkinson disease
Progressive and extensive dopaminergic degeneration induced by convection-enhanced delivery of 6-hydroxydopamine into the rat striatum: a novel rodent model of Parkinson disease
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DOI：
10.3171/jns.2003.98.1.0136
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发表时间：
2003-01-01
影响因子：
4.1
通讯作者：
Bankiewicz, KS
中科院分区：
文献类型：
--
作者：
Oiwa, Y;Sanchez-Pernaute, R;Bankiewicz, KS
Object.纹状体多巴胺损伤诱导啮齿动物进行性黑质变性;然而，纹状体内注射6-羟基多巴胺（6-OHDA）由于存活神经元的自发再生仅引起有限的损伤。为了制造广泛的损伤，作者使用对流增强递送（CED）方法进行纹状体内输注6-OHDA，并评估帕金森病（PD）模型的动物。用CED法将不同剂量的6-OHDA注入大鼠一侧纹状体。基于形态学、生化和行为学测量评估多巴胺能神经元变性，直至损伤后8周。20 μ g 6-OHDA进入纹状体的CED足以获得进行性和广泛的黑质纹状体损伤，如形态学所定义的。（黑质[SN]中细胞损失> 80%）和生物化学（纹状体多巴胺减少> 95%）标准。病变的程度表现为安非他明（> 6转/分钟）和阿朴吗啡（> 4转/分钟）的稳定转向行为。它也出现在损伤后1周的SN的神经元中的凋亡标记物是最大的。应用6-OHDA纹状体内CED成功地建立了一种进行性广泛多巴胺损害的PD大鼠模型。在该模型中，可以使用行为、生物化学和组织化学测量来评估治疗价值。黑质神经元死亡相对于6-OHDA给药时间的延迟可能为测试神经保护策略提供治疗窗口。
Object. A striatal dopamine lesion induces progressive nigral degeneration in rodents; however, intrastriatal injection of 6-hydroxydopamine (6-OHDA) causes only limited lesions due to spontaneous regeneration of the neurons that survive. To make an extensive lesion, the authors used a convection-enhanced delivery (CED) method for intrastriatal infusion of 6-OHDA and evaluated the animals for a model of Parkinson disease (PD).Methods. Different doses of 6-OHDA were infused into the unilateral striatum in rats by using the CED method. The dopaminergic neuronal degeneration was evaluated based on morphological, biochemical, and behavioral measurements until 8 weeks postlesion.Due to the wide distribution of the drug, CED of 20 mug of 6-OHDA into the striatum was sufficient to obtain a progressive and extensive nigrostriatal lesion as defined by morphological (> 80% cell loss in the substantia nigra [SN]) and biochemical (> 95% decrease in striatal dopamine) criteria. The extent of the lesion manifested as a stable turning behavior with amphetamine (> 6 turns/minute) and apomorphine (> 4 turns/minute). It also appeared that at I week postlesion the apoptotic markers were maximal in neurons of the SN.Conclusions. A rat model of PD with a progressive and extensive dopamine lesion was successfully made by intrastriatal CED of 6-OHDA. In this model, the therapeutic value can be assessed using behavioral, biochemical, and histochemical measurements. The delay of nigral neuronal death with respect to the time of 6-OHDA administration may provide a therapeutic window for testing neuroprotective strategies.