[亨廷顿氏病的动物模型:长期存活大鼠纹状体神经毒性病变的组织病理学变化的发展]。

Yvona Mazurová, Jan Osterreicher, Vera Valousková
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引用次数: 0

摘要

立体定向输注ibotenic (IA)或kainic (KA)酸诱导的大鼠脑神经毒性病变是动物研究中常用的亨廷顿病(HD)模型。HD患者的神经退行性过程持续10-20年。然而,大多数与HD动物模型相关的研究只涉及存活数周的动物。因此,本研究详细描述了大鼠大脑纹状体组织病理学变化的发展。在纹状体内注入IA或KA可引起纹状体部分坏死,并伴有神经细胞的萎缩。由于随后在原位增殖的胶质细胞(主要是星形胶质细胞)数量相当少,整个过程导致纹状体萎缩,侧脑室扩大。虽然预期在注射神经毒性酸后1周出现完全发育的IA病变,3-4周出现KA病变,但纹状体内的退行性过程需要相当长的时间——至少6个月。唯一与HD患者的发现不相关的形态学观察是针径区,由明显的神经胶质或神经胶质纤维化疤痕修复。在我们的研究中使用的两种神经毒性酸的组织病理学特征没有实质性差异。然而,如果与只注射一次KA相比,IA必须应用于每个半球的3-4个位置,从形态学的角度来看,KA的使用与人工针迹区域的数量有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[An animal model of Huntington's disease: the development of histopathological changes within the neurotoxic lesions of the striatum in long-term surviving rats].

The neurotoxic lesion of the rat brain, induced by stereotaxic infusion of the ibotenic (IA) or kainic (KA) acids, is a commonly used model of Huntington's disease (HD) in animal studies. Neurodegenerative process in HD develops for 10-20 years. However, the majority of studies related to the animal models of HD deal with only the several weeks surviving animals. For that reason, a detailed description of the development of histopathological changes in the striatum in the rat brain is presented in this study. Intrastriatal instillation of both, the IA or the KA causes the partial necrosis of the striatum, accompanied by a rarefaction of the neuropil. Owing to a rather low number of subsequently in situ proliferating glial cells, predominantly astrocytes, the whole process results in a shrinkage of the striatum compensated by an enlargement of the lateral brain ventricles. Although, the fully developed IA lesion is envisaged at 1 week and KA lesion at 3-4 weeks after the injection of neurotoxic acids, the degenerative process within the striatum develops in a rather long time -- at least 6 months. The only morphological observation that doesn't correlate to the findings from the HD patients, is the needle-track area, which is repaired by a conspicuous glial or glial-fibrotic scar. There is no substantial difference in the histopathological characteristics of both the neurotoxic acids used in our studies. However, if the IA must be applied into 3-4 sites in each hemisphere in comparison with only one injection of the KA, the use of KA is, from the morphological point of view, more suitable in relation to the number of artificial needle-track areas.

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