Graft placement and uneven pattern of reinnervation in the striatum is important for development of graft-induced dyskinesia
In two recent double-blind clinical trials of fetal ventral mesencephalic cell transplants into the striatum in patients with Parkinson's disease (PD), a significant proportion of the grafted patients developed dyskinetic side effects, which were not seen in the sham operated patients. Comparis...
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doaj-d9298519bc2147b29208360ae35020fa2021-03-20T04:52:04ZengElsevierNeurobiology of Disease1095-953X2006-03-01213657668Graft placement and uneven pattern of reinnervation in the striatum is important for development of graft-induced dyskinesiaThomas Carlsson0Christian Winkler1Martin Lundblad2M. Angela Cenci3Anders Björklund4Deniz Kirik5Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, BMC A11, 221 84, Lund, Sweden; Corresponding author. Fax: +46 46 2223436.Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, BMC A11, 221 84, Lund, Sweden; Department of Neurology, Hannover Medical School, 30625 Hannover, GermanyWallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, BMC A11, 221 84, Lund, SwedenWallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, BMC A11, 221 84, Lund, SwedenWallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, BMC A11, 221 84, Lund, SwedenWallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, BMC A11, 221 84, Lund, SwedenIn two recent double-blind clinical trials of fetal ventral mesencephalic cell transplants into the striatum in patients with Parkinson's disease (PD), a significant proportion of the grafted patients developed dyskinetic side effects, which were not seen in the sham operated patients. Comparison between dyskinetic and non-dyskinetic grafted patients in one of the trials suggested that an uneven pattern of striatal reinnervation might be the leading cause of the dyskinesias. Here, we studied the importance of graft placement for the development of dyskinesias in parkinsonian rats. Abnormal involuntary movements resembling peak-dose dyskinesias seen in PD patients were induced by daily injections of l-DOPA for 6 weeks. The dyskinetic animals received about 130.000 fetal ventral mesencephalic cells as single grafts placement in the rostral or the caudal aspect of the head of striatum. The results show that grafts placed in the caudal, but not the rostral, part are effective in reducing the l-DOPA-induced limb and orolingual dyskinesia, predominantly seen as hyperkinesia. The same grafts, however, also induced a new type of dyskinetic behavior after activation with amphetamine, which were not seen in non-grafted lesion controls. The severity of these abnormal involuntary movements was significantly correlated with a higher graft-derived dopaminergic reinnervation in the caudal aspect of the head of striatum relative to the rostral part. The results indicate that graft-induced dyskinesias in PD patients may be linked to single, small graft deposits that provide an uneven, patchy reinnervation of the putamen.http://www.sciencedirect.com/science/article/pii/S0969996105002536Parkinson's diseaseDyskinesial-DOPACell transplantationVentral mesenchephalonMotor behavior |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Thomas Carlsson Christian Winkler Martin Lundblad M. Angela Cenci Anders Björklund Deniz Kirik |
spellingShingle |
Thomas Carlsson Christian Winkler Martin Lundblad M. Angela Cenci Anders Björklund Deniz Kirik Graft placement and uneven pattern of reinnervation in the striatum is important for development of graft-induced dyskinesia Neurobiology of Disease Parkinson's disease Dyskinesia l-DOPA Cell transplantation Ventral mesenchephalon Motor behavior |
author_facet |
Thomas Carlsson Christian Winkler Martin Lundblad M. Angela Cenci Anders Björklund Deniz Kirik |
author_sort |
Thomas Carlsson |
title |
Graft placement and uneven pattern of reinnervation in the striatum is important for development of graft-induced dyskinesia |
title_short |
Graft placement and uneven pattern of reinnervation in the striatum is important for development of graft-induced dyskinesia |
title_full |
Graft placement and uneven pattern of reinnervation in the striatum is important for development of graft-induced dyskinesia |
title_fullStr |
Graft placement and uneven pattern of reinnervation in the striatum is important for development of graft-induced dyskinesia |
title_full_unstemmed |
Graft placement and uneven pattern of reinnervation in the striatum is important for development of graft-induced dyskinesia |
title_sort |
graft placement and uneven pattern of reinnervation in the striatum is important for development of graft-induced dyskinesia |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2006-03-01 |
description |
In two recent double-blind clinical trials of fetal ventral mesencephalic cell transplants into the striatum in patients with Parkinson's disease (PD), a significant proportion of the grafted patients developed dyskinetic side effects, which were not seen in the sham operated patients. Comparison between dyskinetic and non-dyskinetic grafted patients in one of the trials suggested that an uneven pattern of striatal reinnervation might be the leading cause of the dyskinesias. Here, we studied the importance of graft placement for the development of dyskinesias in parkinsonian rats. Abnormal involuntary movements resembling peak-dose dyskinesias seen in PD patients were induced by daily injections of l-DOPA for 6 weeks. The dyskinetic animals received about 130.000 fetal ventral mesencephalic cells as single grafts placement in the rostral or the caudal aspect of the head of striatum. The results show that grafts placed in the caudal, but not the rostral, part are effective in reducing the l-DOPA-induced limb and orolingual dyskinesia, predominantly seen as hyperkinesia. The same grafts, however, also induced a new type of dyskinetic behavior after activation with amphetamine, which were not seen in non-grafted lesion controls. The severity of these abnormal involuntary movements was significantly correlated with a higher graft-derived dopaminergic reinnervation in the caudal aspect of the head of striatum relative to the rostral part. The results indicate that graft-induced dyskinesias in PD patients may be linked to single, small graft deposits that provide an uneven, patchy reinnervation of the putamen. |
topic |
Parkinson's disease Dyskinesia l-DOPA Cell transplantation Ventral mesenchephalon Motor behavior |
url |
http://www.sciencedirect.com/science/article/pii/S0969996105002536 |
work_keys_str_mv |
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