gms | German Medical Science

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

Characterisation of sensorimotor behavioral deficits comparing partial and complete 6-OHDA lesions depending on the performance prior to lesion in a rat Parkinson model

Meeting Abstract

  • M. Timmer - Neurochirurgische Klinik und Poliklinik, Klinikum Großhadern, Ludwig-Maximilians-Universität, München
  • C. Winkler - Neurologische Universitätsklinik, Albert-Ludwigs-Universität, Freiburg
  • A. Klein - Brain Repair Group, Cardiff School of Biosciences, UK
  • G. Nikkhah - Abteilung Stereotaktische und Funktionelle Neurochirurgie, Neurochirurgische Universitätsklinik, Albert-Ludwigs-Universität, 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. DocMO.13-07

DOI: 10.3205/09dgnc095, URN: urn:nbn:de:0183-09dgnc0954

Published: May 20, 2009

© 2009 Timmer et al.
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Outline

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Objective: Different animal models of Parkinson's disease (PD) are used in order to develop and evaluate new therapies including e.g. deep brain stimulation and stem cell transplantation. Terminal 6-OHDA lesions of the rat striatum represent more closely early and middle stages of human idiopathic PD, whereas the medial forebrain bundle (MFB) lesion corresponds to a more complete destruction of the dopaminergic nigrostriatal pathway seen in late PD stages. In the present study, both 6-OHDA lesion models were compared. We investigated the impact of motor training prior to the lesion on functional recovery and morphological pathway destruction after unilateral MFB-lesion versus striatal lesions in an animal model.

Methods: The experiment included 7 groups (n=12 rats each): MFB- and terminal-lesioned rats with or without prelesion training and respective control groups. Complex behavioral performance was investigated immediately after and 1, 2 and 4 months postlesion. Finally, TH-immunohistochemistry and dopamine measurements using HPLC were performed to confirm the extent of the lesion and to analyse the dependency on behavior.

Results: Rats with MFB-lesions display both apomorphine- (–6.8 turns per minute (tpm)) and amphetamine-(+7.8tpm)-induced rotations while the partially lesioned groups elicited amphetamine-(+9.4tpm)-induced rotations only. The table lift test showed that trained animals with MFB-lesions show better behavioral levels four months post lesion compared to untrained animals (p<0.01), whereas the training levels had no influence in partially lesioned animals. The outcome in the latter behavioral test was dependent on the amount of dopamine measured in the medial caudate putamen unit. Other statistically significant differences included a more pronounced deficit in skilled forelimb use for the untrained rats (2.9 pellets eaten) as compared to the pretrained rats (16 pellets eaten) in the groups with MFB lesions (p<0.001), as well as generally more pronounced deficits in the MFB-lesioned groups as compared to the terminal-lesioned groups.

Conclusions: The degree of sensorimotor deficits is highly correlated with the extent of nigrostriatal pathway destruction. In addition, prelesion motor training can significantly improve postlesion recovery. These data may provide further insights into the functional organisation of the basal ganglia and for the optimisation of neuroprotective and restorative treatment strategies.