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.

Univerzita Karlova Praha Lékarská fakulta v Hradci Králové Ustav histologie a embryologie

An animal model of Huntington's disease: the development of histopathological changes within the neurotoxic lesions of the striatum in long-term surviving rats