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

Effects of double-grafting on the survival of embryonal (E14) mesencephalic dopaminergic neurons transplanted in a rat model of Parkinson’s disease (PD)

Der Einfluss zweizeitiger Transplantation auf das Überleben embryonaler (E14) mesenzephaler dopaminerger Neurone nach Implantation im Tiermodell der Parkinson’schen Erkrankung

Meeting Abstract

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  • corresponding author C. Hackl - Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Neurozentrum, Universitätsklinikum Freiburg
  • A. Papazoglou - Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Neurozentrum, Universitätsklinikum Freiburg
  • A. Klein - Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Neurozentrum, Universitätsklinikum Freiburg
  • G. Nikkhah - Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Neurozentrum, Universitätsklinikum 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. DocP029

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2005/05dgnc0297.shtml

Veröffentlicht: 4. Mai 2005

© 2005 Hackl 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

A rat model of PD is based on unilateral injections of 6-hydroxydopamine (6-OHDA) into the mid forebrain bundle of the rat, resulting in a complete loss of nigral dopaminergic (DAergic) neurons and leading to a depletion of dopamine within the relevant striatum. Six weeks after the lesion, primary cell suspensions rich in DAergic neurons, derived from dissociated ventral mesencephalon (VM) of E14 rat embryos, are transplanted into the lesioned striatum. However, only 8-10% of the DAergic neurons survive and lead to a partial functional recovery. In order to improve the survival and functional integration of the grafted cells, we established a new protocol based on two transplantation time points.

Methods

During the first transplantation, 6-OHDA lesioned rats received half of the standard amount of VM cell suspension (200,000 cells). At defined time points of 3, 5, 7 or 9 days after the first transplantations, the animals received a second graft (200,000 cells), placed in the middle of the first graft. One further group were treated according to the standard protocol. Lesion and transplantation effects were evaluated by apomorphine and amphetamine induced rotations, performed 6 weeks after lesion and 2, 5, 9 and 14 weeks after the first grafting. Survival of DAergic neurons and graft volume were assessed.

Results

A significant difference was observed in the two weeks amphetamine-induced rotation between the groups 3 and 7 days; 5 and 7 days; 3 and 9 days. Morphological and stereological analysis showed a significantly higher cell number in the group of 5 days as compared to the groups 7 days (+111%) and 9 days (+97%) as well as compared to the standard transplantation protocol (+77%). The graft-volume in the group 5 days is significantly higher than in the group 7 days (+130%) and also shows a strong tendency to be higher than the group 9 days (+66%).

Conclusions

Recent publications have shown that the neonatal brain exhibits a higher plasticity, survival and functional integration of grafts compared to the adult brain. In principle, our first graft should simulate the embryonal microenvironment within the lesioned striatum for a better integration of the second graft. Taken together, the double-grafting strategy offers an interesting model to promote graft survival and integration as wells as graft-host-interactions in Parkinson’s disease.