Publikation:

Improvement of embryonic dopaminergic neurone survival in culture and after grafting into the striatum of hemiparkinsonian rats by CEP-1347

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2004

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Boll, Jette Bisgaard
Geist, Marie Aavang
Kaminski Schierle, Gabriele S.
Petersen, Karina
Vaudano, Elisabetta

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http://nbn-resolving.de/urn:nbn:de:bsz:352-2--u5uuz6uskiy0
DOI (zitierfähiger Link)
https://doi.org/10.1046/j.1471-4159.2003.02198.x
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Open Access Green

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Biologie: Publikationen
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Journal of Neurochemistry. 2004, 88(3), pp. 698-707. ISSN 0022-3042. eISSN 1471-4159. Available under: doi: 10.1046/j.1471-4159.2003.02198.x

Zusammenfassung

Transplantation of embryonic nigral tissue ameliorates functional deficiencies in Parkinson's disease (PD). A main constraint of neural grafting is the poor survival of dopaminergic neurones grafted into patients. Studies in rats indicated that many grafted neurones die by apoptosis. CEP-1347 is a mixed-lineage-kinase (MLK) inhibitor with neuroprotective action in several in vitro and in vivo models of neuronal apoptosis. We studied the effect of CEP-1347 on the survival of embryonic rat dopaminergic neurones in culture, and after transplantation in hemiparkinsonian rats. CEP-1347 and the alternative MLK inhibitor CEP-11004 significantly increased the survival of dopaminergic neurones in primary cultures from rat ventral mesencephalon and in Mn2+-exposed PC12 cells, a surrogate model of dopaminergic lethal stress. Moreover, combined treatment of the grafting cell suspension and the host animal with CEP-1347 significantly improved the long-term survival of rat dopaminergic neurones transplanted into the striatum of hemiparkinsonian rats. Also, the protective effect of CEP-1347 resulted in an increase in total graft size and in enhanced fibre outgrowth. Thus, treatment with CEP-1347 improved dopaminergic cell survival under severe stress and might be useful to improve the positive outcome of transplantation therapy in PD and reduce the amount of human tissue required.

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570 Biowissenschaften, Biologie

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ISO 690BOLL, Jette Bisgaard, Marie Aavang GEIST, Gabriele S. KAMINSKI SCHIERLE, Karina PETERSEN, Marcel LEIST, Elisabetta VAUDANO, 2004. Improvement of embryonic dopaminergic neurone survival in culture and after grafting into the striatum of hemiparkinsonian rats by CEP-1347. In: Journal of Neurochemistry. 2004, 88(3), pp. 698-707. ISSN 0022-3042. eISSN 1471-4159. Available under: doi: 10.1046/j.1471-4159.2003.02198.x
BibTex
@article{Boll2004-02Impro-40637,
  year={2004},
  doi={10.1046/j.1471-4159.2003.02198.x},
  title={Improvement of embryonic dopaminergic neurone survival in culture and after grafting into the striatum of hemiparkinsonian rats by CEP-1347},
  number={3},
  volume={88},
  issn={0022-3042},
  journal={Journal of Neurochemistry},
  pages={698--707},
  author={Boll, Jette Bisgaard and Geist, Marie Aavang and Kaminski Schierle, Gabriele S. and Petersen, Karina and Leist, Marcel and Vaudano, Elisabetta}
}
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