gms | German Medical Science

56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
3èmes journées françaises de Neurochirurgie (SFNC)

Deutsche Gesellschaft für Neurochirurgie e. V.
Société Française de Neurochirurgie

07. bis 11.05.2005, Strasbourg

Mechanisms of functional restoration of dopaminergic grafts in a rat model of Parkinson’s disease

Mechanismen der funktionalen Restauration dopaminerger Transplantate im Tiermodell der Parkinson’schen Krankheit

Meeting Abstract

  • corresponding author A. Klein - Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Universitätsklinikum Freiburg - Neurozentrum, Freiburg
  • G. A. Metz - Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada
  • V. Kloth - Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Universitätsklinikum Freiburg - Neurozentrum, Freiburg
  • A. Papazoglou - Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Universitätsklinikum Freiburg - Neurozentrum, Freiburg
  • M. Knieling - Universitätsklinikum Jena, Abt. für Neurologie, Jena
  • G. Nikkhah - Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Universitätsklinikum Freiburg - Neurozentrum, Freiburg

Deutsche Gesellschaft für Neurochirurgie. Société Française de Neurochirurgie. 56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3èmes journées françaises de Neurochirurgie (SFNC). Strasbourg, 07.-11.05.2005. Düsseldorf, Köln: German Medical Science; 2005. DocP028

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2005/05dgnc0296.shtml

Veröffentlicht: 4. Mai 2005

© 2005 Klein et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

Unilateral injections of 6-OHDA into the rat medial forebrain bundle (MFB) lead to permanent motor impairments in skilled limb movements (SLM), gait performance and spontaneous behaviour. It is well known that motor training (e.g. running wheel) and housing in an enriched environment ameliorate lesioned-induced impairments, generate neurogenesis and may have neuroprotective effects. Also foetal dopaminergic (DAergic) grafts promote an improvement of sensorimotor behaviour in hemiparkinsonian rats. The aim of this study was to investigate therapeutical effects of different levels of motor training and transplantation of foetal DAergic neurons on motor performance in a rat model of Parkinson’s disease (PD).

Methods

The rats (n=29) were trained in spontaneous behavioural tests (table lift test, side stepping/side falling test), and skilled reaching tasks (single pellet grasping task for qualitative and quantitative evaluation; staircase test for quantitative evaluation). Gait analysis (rung walking task and footprint analysis) was performed to test skilled walking and forelimb/hindlimb coordination. After MFB-6-OHDA lesion and intrastriatal transplantation of foetal E14 VM neurons, rotational behaviour was assessed.

Results

After transplantation, the grafted rats showed an overcompensation under amphetamine administration (+15.5rpm before the transplantation to -8.9rpm after the transplantation) and a reduction of apomorphine-induced rotation (-12.3rpm to -5.4rpm). This indicates a significant graft survival and graft effect on simple motor behaviour. Morphological and stereological analyses demonstrated substantial graft survival and reinnervation (29% improvement of fibre density in grafted rats compared to lesioned ones). For gait performance an incomplete but significant improvement (20-45%) after transplantation could be observed. The quantitative evaluation of SLM demonstrated significant enhancement (10%) whereas the qualitative analysis revealed no improving graft effect. Training at different time points before and after the lesion and/or transplantation showed a considerable time-dependent influence on grafted cells and integration of foetal neurons in the host striatum.

Conclusions

We conclude that in hemiparkinsonian rats graft-induced recovery in SLM is due to graft-induced compensatory mechanisms and that motor training has a supporting influence on transplanted neurons.

This study was supported by DFG and AHFMR.