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59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

01. - 04.06.2008, Würzburg

Micro-transplantation in a quinolinic acid induced rodent model of Huntington's disease

Mikrotransplantation in ein Quinolinsäure-induziertes Ratten-Modell der Huntington Erkrankung

Meeting Abstract

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  • corresponding author W. Jiang - Labor Molekulare Neurochirurgie, Abteilung Stereotaktische und Funktionelle Neurochirurgie, Universitätsklinikum Freiburg
  • J. Garcia - Labor Molekulare Neurochirurgie, Abteilung Stereotaktische und Funktionelle Neurochirurgie, Universitätsklinikum Freiburg
  • A. Papazoglou - Labor Molekulare Neurochirurgie, Abteilung Stereotaktische und Funktionelle Neurochirurgie, Universitätsklinikum Freiburg
  • G. Nikkhah - Labor Molekulare Neurochirurgie, Abteilung Stereotaktische und Funktionelle Neurochirurgie, Universitätsklinikum Freiburg

Deutsche Gesellschaft für Neurochirurgie. Società Italiana di Neurochirurgia. 59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch). Würzburg, 01.-04.06.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocP 028

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2008/08dgnc296.shtml

Veröffentlicht: 30. Mai 2008

© 2008 Jiang 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: Neural transplantation has been demonstrated to be an optional treatment for Huntington's disease (HD), but problems still remain in the availability of suitable donor tissues and defining optimal conditions for reliable survival of implanted cells. In this study, we investigated the different neuroanatomical and behavioural effects between single- (ST) and multi-tracts (MT) transplants performed in a HD rodent model.

Methods: 34 Sprague Dawley rats received unilateral quinolinic acid injections into the left striatum. 10 days after the quinolinic acid lesion the animals were transplanted with a single cell suspension rich in GABAergic progenitor derived from the striatum of E15 rat embryos. Animals were grafted by ST (1 tract/2 deposits) or MT (9 tracts/18 deposits) using a micro pump and a 2µl Hamilton’s syringe with capillary. Both groups were injected with 480,000 cells in total. Animals were trained prior to lesion and 4, 8, 12 weeks post transplantation in spontaneous behaviour and skilled forelimb use. Lesion and graft evaluation was performed by apomorphine-induced rotation 7 days after lesion and 4, 8, and 12 weeks after transplantation. MRI scan was used to detect the survival, migration, and integration of the intrastriatal grafted cells. After perfusion, the brains was processed for immunohistochemistry. Graft volume and cell survival was accessed by stereology.

Results: Two months after transplantation, MT group improved by 15% compared to the ST group in the side stepping test. In addition, the MT as well as the ST group improved by 40% and 30% respectively in the side stepping test compared to the sham group. However, all groups show similar behaviour with no significance difference (p<0.05) in the stair case test and rotation test. MRI scans presented clearly the lesion effect of quinolinic acid in the left striatum of the animals; an effect that can be correlated to the behaviour performance of the animals. Darpp32 immunostaining revealed the degeneration of GABAergic cells in the striatum and graft survival and integration.

Conclusions: Stepping test can be used as a sensitive method to check the quinonilic acid induced lesion and the recovery after transplantation of E15 striatal cells. MT graft compared to ST has a beneficial outcome. MRI provides a noninvasive tool useful for in vivo visualization of the anatomic changes produced by excitotoxic lesions in animals and also for monitoring in vivo graft survival and development. Taken together, the micro transplantation approach may offer significant advantages for HD as was shown for Parkinson's disease.