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Grealish, S,Xie, L,Kelly, M,Dowd, E
2008
November
Brain Research Bulletin
Unilateral axonal or terminal injection of 6-hydroxydopamine causes rapid-onset nigrostriatal degeneration and contralateral motor impairments in the rat
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Parkinson's disease Animal models 6-Hydroxydopamine Striatum Medial forebrain bundle Motor function MIDBRAIN DOPAMINERGIC-NEURONS CENTRAL MONOAMINE NEURONS INTRASTRIATAL 6-HYDROXYDOPAMINE SUBSTANTIA-NIGRA CORRIDOR TASK LESION MODEL STRIATUM RECOVERY SURVIVAL SYSTEM
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Unilateral injection of the catecholamine neurotoxin 6-hydroxydopamine into the axons or terminals of the nigrostriatal pathway is commonly used to model Parkinson's disease in experimental animals. Although the terminal lesion paradigm is considered to induce a more progressive lesion when compared to the axonal lesion, few studies have directly compared the early time-course for lesion development in these two models. Thus, this experiment sought to establish the temporal pattern of nigrostriatal degeneration and emergence of contralateral motor impairment in these models. Young adult male Lister Hooded rats were used. After baseline testing on a battery of spontaneous motor tests, standard stereotaxic techniques were used to inject 6-hydroxydopamine into the nigrostriatal axons or terminals at the level of the medial forebrain bundle or striatum respectively. From the day after lesion surgery, a subset of the rats was tested for motor performance, while another subset was used for immunohistochemical analysis. Quantitative tyrosine hydroxylase immunohistochemistry revealed that although both lesions caused a similar temporal pattern of immunopositive cell loss from the substantia nigra, the terminal lesion caused a more rapid loss of immunopositive terminals from the striatum. Despite these differences in striatal dopaminergic deafferentation, both lesion types caused a profound loss of contralateral motor function from the first day after lesion surgery. These findings illustrate the rapidity of the neuropathological and behavioural consequences of either axonal or terminal injection of 6-hydroxydopamine into the nigrostriatal pathway, and further highlight the need for a more progressive model of human Parkinson's disease. (C) 2008 Elsevier Inc. All rights reserved.
DOI 10.1016/j.brainresbull.2008.08.018
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