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60th Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Benelux countries and Bulgaria

German Society of Neurosurgery (DGNC)

24 - 27 May 2009, Münster

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Neurotransplantation in Parkinson’s disease: Role of serotonin neurons within the graft suspension for the expression of L-DOPA- and Graft-induced dyskinesia

Meeting Abstract

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  • J. Garcia - Klinik für Neurochirurgie, Neurozentrum, Universitätsklinikum Freiburg
  • T. Carlsson - AG Experimentelle Neurologie, Philipps-Universität Marburg
  • G. Nikkhah - Klinik für Neurochirurgie, Neurozentrum, Universitätsklinikum Freiburg
  • C. Winkler - Klinik für Neurologie, Neurozentrum, Universitätsklinikum Freiburg

Deutsche Gesellschaft für Neurochirurgie. 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien. Münster, 24.-27.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. DocP07-04

doi: 10.3205/09dgnc320, urn:nbn:de:0183-09dgnc3200

Published: May 20, 2009

© 2009 Garcia et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: Transplantation of fetal dopamine neurons as a new therapeutic approach for Parkinson’s disease (PD) patients has given inconsistent results. While some patients showed profound reduction of motor deficits, others showed only minor improvements. Although L-DOPA-induced dyskinesia (LID) was reduced in most of the cases, some showed a new type known as graft-induced dyskinesia (GID). One of the possible reasons for the development of GID is the composition of the grafts since they contain large numbers of serotonin neurons in addition to dopamine neurons. Previous studies in a rat Parkinson model have shown that dopamine grafts reduce LID but may induce GID, while serotonin neurons can worsen LID. Therefore, the aim of the present study was to further characterize the changes of LID and GID in relation to different proportions of dopamine and serotonin neurons within a graft.

Methods: 120 rats received unilateral complete dopamine-denervating lesions by injection of 6-OHDA into the medial forebrain bundle (MFD). The severity of the lesion was evaluated using amphetamine-induced rotation and the performance in spontaneous motor behavior (cylinder and corridor tests). Animals then received daily injections of L-DOPA (6mg/kg) and benserazide (10mg/kg) for 4 weeks, and LID was evaluated according to a rat dyskinesia scale, followed by intrastriatal grafts of fetal dopamine and serotonin cells. The ratio of transplanted dopamine versus serotonin cells in the different experimental groups was 2:1, 1:1, 1:2, 1:4. The expression of LID is scored at 2, 4, 12, and 14, and of GID at 5 and 15 weeks post-grafting. In addition, graft-induced changes in amphetamine-induced rotation and spontaneous motor behavior were evaluated.

Results: Amphetamine-induced-rotation and spontaneous behavior tests showed a clear deficit on the side contralateral to the lesion. The animals demonstrated ipsilateral paw's preference in 87.8% in the cylinder test and in 85.6% in the corridor test; L-DOPA therapy induced all types of LID, the limb and axial type being the most common ones. Two weeks after the transplantation LID was evaluated, and no significant changes were found.

Conclusions: This study determines the optimal ratio between dopamine and serotonin cells that provides a good motor benefit with little risk of development of dopamine-dependent dyskinesia. The results provide useful and important information for further developments in neural transplantation for PD.