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High correlation between in vivo [(123)I]β-CIT SPECT/CT imaging and post-mortem immunohistochemical findings in the evaluation of lesions induced by 6-OHDA in rats

BACKGROUND: 6-Hydroxydopamine (6-OHDA) is widely used in pre-clinical animal studies to induce degeneration of midbrain dopamine neurons to create animal models of Parkinson's disease. The aim of our study was to evaluate the potential of combined single-photon emission computed tomography/comp...

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Autores principales: Bäck, Susanne, Raki, Mari, Tuominen, Raimo K, Raasmaja, Atso, Bergström, Kim, Männistö, Pekka T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689076/
https://www.ncbi.nlm.nih.gov/pubmed/23758882
http://dx.doi.org/10.1186/2191-219X-3-46
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author Bäck, Susanne
Raki, Mari
Tuominen, Raimo K
Raasmaja, Atso
Bergström, Kim
Männistö, Pekka T
author_facet Bäck, Susanne
Raki, Mari
Tuominen, Raimo K
Raasmaja, Atso
Bergström, Kim
Männistö, Pekka T
author_sort Bäck, Susanne
collection PubMed
description BACKGROUND: 6-Hydroxydopamine (6-OHDA) is widely used in pre-clinical animal studies to induce degeneration of midbrain dopamine neurons to create animal models of Parkinson's disease. The aim of our study was to evaluate the potential of combined single-photon emission computed tomography/computed tomography (SPECT/CT) for the detection of differences in 6-OHDA-induced partial lesions in a dose- and time-dependent manner using the dopamine transporter (DAT) ligand 2β-carbomethoxy-3β-(4-[(123)I]iodophenyl)tropane ([(123)I]β-CIT). METHODS: Rats were unilaterally lesioned with intrastriatal injections of 8 or 2 × 10 μg 6-OHDA. At 2 or 4 weeks post-lesion, 40 to 50 MBq [(123)I]β-CIT was administered intravenously and rats were imaged with small-animal SPECT/CT under isoflurane anesthesia. The striatum was delineated and mean striatal activity in the lesioned side was compared to the intact side. After the [(123)I]β-CIT SPECT/CT scan, the rats were tested for amphetamine-induced rotation asymmetry, and their brains were immunohistochemically stained for DAT and tyrosine hydroxylase (TH). The fiber density of DAT- and TH-stained striata was estimated, and TH-immunoreactive cells in the rat substantia nigra pars compacta (SNpc) were stereologically counted. RESULTS: The striatal uptake of [(123)I]β-CIT differed significantly between the lesion groups and the results were highly correlated to both striatal DAT- and TH-immunoreactive fiber densities and to TH-immunoreactive cell numbers in the rat SNpc. No clear progression of the lesion could be seen. CONCLUSIONS: [(123)I]β-CIT SPECT/CT is a valuable tool in predicting the condition of the rat midbrain dopaminergic pathway in the unilateral partial 6-OHDA lesion model of Parkinson's disease and it offers many advantages, allowing repeated non-invasive analysis of living animals.
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spelling pubmed-36890762013-06-25 High correlation between in vivo [(123)I]β-CIT SPECT/CT imaging and post-mortem immunohistochemical findings in the evaluation of lesions induced by 6-OHDA in rats Bäck, Susanne Raki, Mari Tuominen, Raimo K Raasmaja, Atso Bergström, Kim Männistö, Pekka T EJNMMI Res Original Research BACKGROUND: 6-Hydroxydopamine (6-OHDA) is widely used in pre-clinical animal studies to induce degeneration of midbrain dopamine neurons to create animal models of Parkinson's disease. The aim of our study was to evaluate the potential of combined single-photon emission computed tomography/computed tomography (SPECT/CT) for the detection of differences in 6-OHDA-induced partial lesions in a dose- and time-dependent manner using the dopamine transporter (DAT) ligand 2β-carbomethoxy-3β-(4-[(123)I]iodophenyl)tropane ([(123)I]β-CIT). METHODS: Rats were unilaterally lesioned with intrastriatal injections of 8 or 2 × 10 μg 6-OHDA. At 2 or 4 weeks post-lesion, 40 to 50 MBq [(123)I]β-CIT was administered intravenously and rats were imaged with small-animal SPECT/CT under isoflurane anesthesia. The striatum was delineated and mean striatal activity in the lesioned side was compared to the intact side. After the [(123)I]β-CIT SPECT/CT scan, the rats were tested for amphetamine-induced rotation asymmetry, and their brains were immunohistochemically stained for DAT and tyrosine hydroxylase (TH). The fiber density of DAT- and TH-stained striata was estimated, and TH-immunoreactive cells in the rat substantia nigra pars compacta (SNpc) were stereologically counted. RESULTS: The striatal uptake of [(123)I]β-CIT differed significantly between the lesion groups and the results were highly correlated to both striatal DAT- and TH-immunoreactive fiber densities and to TH-immunoreactive cell numbers in the rat SNpc. No clear progression of the lesion could be seen. CONCLUSIONS: [(123)I]β-CIT SPECT/CT is a valuable tool in predicting the condition of the rat midbrain dopaminergic pathway in the unilateral partial 6-OHDA lesion model of Parkinson's disease and it offers many advantages, allowing repeated non-invasive analysis of living animals. Springer 2013-06-10 /pmc/articles/PMC3689076/ /pubmed/23758882 http://dx.doi.org/10.1186/2191-219X-3-46 Text en Copyright ©2013 Bäck et al.; licensee Springer. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Bäck, Susanne
Raki, Mari
Tuominen, Raimo K
Raasmaja, Atso
Bergström, Kim
Männistö, Pekka T
High correlation between in vivo [(123)I]β-CIT SPECT/CT imaging and post-mortem immunohistochemical findings in the evaluation of lesions induced by 6-OHDA in rats
title High correlation between in vivo [(123)I]β-CIT SPECT/CT imaging and post-mortem immunohistochemical findings in the evaluation of lesions induced by 6-OHDA in rats
title_full High correlation between in vivo [(123)I]β-CIT SPECT/CT imaging and post-mortem immunohistochemical findings in the evaluation of lesions induced by 6-OHDA in rats
title_fullStr High correlation between in vivo [(123)I]β-CIT SPECT/CT imaging and post-mortem immunohistochemical findings in the evaluation of lesions induced by 6-OHDA in rats
title_full_unstemmed High correlation between in vivo [(123)I]β-CIT SPECT/CT imaging and post-mortem immunohistochemical findings in the evaluation of lesions induced by 6-OHDA in rats
title_short High correlation between in vivo [(123)I]β-CIT SPECT/CT imaging and post-mortem immunohistochemical findings in the evaluation of lesions induced by 6-OHDA in rats
title_sort high correlation between in vivo [(123)i]β-cit spect/ct imaging and post-mortem immunohistochemical findings in the evaluation of lesions induced by 6-ohda in rats
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689076/
https://www.ncbi.nlm.nih.gov/pubmed/23758882
http://dx.doi.org/10.1186/2191-219X-3-46
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