gms | German Medical Science

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

Transplantation of embryonic stem cells dramatically improves the neurological outcome after traumatic brain injury, possibly mediated by release of neurotrophic factors

Stammmzell-induzierte Verbesserung der neurologischen Funktionen nach experimentellen Schädel-Hirn-Trauma scheint auf die Sekretion neurotropher Faktoren zurückzuführen zu sein

Meeting Abstract

  • corresponding author M. Molcanyi - Zentrum für Neurochirurgie, Universitätsklinikum Köln
  • P. Riess - Lehrstuhl für Unfallchirurgie und Orthopädie in Köln-Merheim, Universität Witten-Herdecke
  • J. Hescheler - Neurophysiologisches Institut, Universität zu Köln
  • R. I. Ernestus - Zentrum für Neurochirurgie, Universitätsklinikum Köln
  • E. Neugebauer - Institut für Forschung in der Operativen Medizin (IFOM) in Köln-Merheim, Universität Witten-Herdecke
  • U. Schäfer - Institut für Forschung in der Operativen Medizin (IFOM) in Köln-Merheim, Universität Witten-Herdecke

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. DocDI.04.09

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2008/08dgnc175.shtml

Veröffentlicht: 30. Mai 2008

© 2008 Molcanyi 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

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Objective: To improve the outcome of traumatic brain injury, we transplanted undifferentiated murine embryonic stem cells (ES cells), having potential to replace all types of lost brain cells (neurons, astrocytes, oligodendrocytes).

Methods: Male Sprague-Dawley rats were subjected to a lateral fluid-percussion injury. 72 hrs. After TBI 1x105 eGFP-transfected ES cells (D3-line) were implanted into ipsi/contralateral cortex (n=20). Control animals received 1,0 ul PBS after TBI (n=13), shams got neither TBI nor PBS (n=13). Immunosuppression was carried out with daily doses of cyclosporine A (10 mg/ KG body weight) for a period of 2 weeks. Animals were sacrificed 5 days and 7 weeks postimplantation. Conventional, fluorescent and confocal histological analysis was performed on paraformaldehyde fixed brain sections using specific antibodies against ES-cells, neural differentiation markers and macrophages. Neurological outcome was measured by Rotarod, Composit Neuroscore and Barnes Circular Maze tests. ELISA was used to evaluate the production of neurotrophic factors in ES cell cultures stimulated by brain supernatant in vitro.

Results: 5 days postimplantation, the clusters of injected ES cells resided at the implantation site and showed the first sings of early neural differentiation. However, 7 weeks postimplantation only few cells have been found. This was due to extensive phagocytosis of the implanted cells. Functional integration of the remaining cells was not observed. Despite the cell loss, statistically significant neurological improvement of sensimotor function was observed in Rotarod and Composite Neuroscore tests over the period of 7 weeks in the group of animals receiving the ES cell transplantation. A significant improvement of cognitive function could not be shown using Barnes Circular Maze test, although a constant rising trend of improvement has been observed. ES-cell cultures stimulated by brain supernatant in-vitro produced statistically significant amount of neurotrophic factors (NGF, BDNF).

Conclusions: We observed a significant improvement of neurological function of the injured brain after receiving ES cell implantation. This could not be due to formation of new neuronal networks based on the implanted ES cells. The improvement was probably mediated by a release of neurotrophic factors from implanted cells, as shown in-vitro.