gms | German Medical Science

55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

Enhanced survival, reinnervation and functional recovery of intrastriatal dopamine grafts co-transplanted with Schwann cells over-expressing high molecular weight FGF-2 in a rat model of Parkinson´s disease

Die Ko-Transplantation von embryonalen dopaminergen Neuronen mit FGF-2-überexprimierenden Schwann-Zellen zeigt eine Verbesserung des Überlebens, der Reinnervation und der funktionellen Erholung im Tiermodell der Parkinsonschen Erkrankung

Meeting Abstract

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  • corresponding author Marco Timmer - Department of Stereotactic and Functional Neurosurgery, Laboratory of Molecular Neurosurgery, Neurocenter, University Hospital, Freiburg; Department of Neuroanatomy, Center of Anatomy, OE 4140, Hannover Medical School, Hannover
  • C. Grothe - Department of Neuroanatomy, Center of Anatomy, OE 4140, Hannover Medical School, Hannover
  • G. Nikkhah - Department of Stereotactic and Functional Neurosurgery, Laboratory of Molecular Neurosurgery, Neurocenter, University Hospital, Freiburg

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocDI.04.11

The electronic version of this article is the complete one and can be found online at:

Published: April 23, 2004

© 2004 Timmer et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.




Transplantation of embryonic ventral mesencephalic (VM) neurons for Parkinson´s disease (PD) is limited by poor survival of grafted dopaminergic (DA) cells. Most of the neurons (up to 90%) die during the grafting procedure or within 6 days following the implantation. The aim of our study was to evaluate different experimental conditions in order to promote DA graft survival and functional reinnervation. We recently demonstrated, that the higher molecular weight (HMW) FGF-2 stimulates the survival of DA neurons in co-cultures. Therefore, we grafted VM dopaminergic neurons together with Schwann cells (SC) over-expressing different FGF-2 isoforms into the striatum of 6-hydroxydopamine lesioned rats.


In a first attempt immortalized SC over-expressing the HMW FGF-2 were co-implanted with DA neurons in a mixed cell suspension and compared with the corresponding control vector. In a second approach we co-grafted physiological SC in a similar way and in the third experiment physiological SC were transplanted side-by-side with DA grafts. Each experiment comprised 6 groups (unilaterally 6-OHDA lesioned rats, n=9 per group): immortalized respectively physiological SC transfected with 18 kD FGF-2 / HMW FGF-2 / control vector and the control group with embryonic dopaminergic cells only. Two different transplantation protocols were used: a mixture of VM cells and SC was grafted in the mixed design, whereas in the side-by-side approach DA and SC were transplanted spatially and temporally separated. Behavioural performance including drug-induced rotation postlesion, 2, 4 and 8 weeks postgrafting, and finally, TH-, ED1, p75 and GFAP immunohistochemistry, HE and cresyl violett staining and BrdU-labeling were performed.


DA neurons co-grafted with HMW FGF-2 over-expressing immortalized SC displayed a two-fold better survival (541 ± 79 TH+ cells) than those co-transplanted with control vector transfected SC (232 ± 41). Transplantation of a mixed suspension containing DA cells and physiological SC showed significant higher number of surviving DA cells in the SC HMW group (1392 ± 106) compared to the remaining groups (984 -147 cells). In amphetamine induced rotation, the SC HMW group compensated first, already 4 weeks after transplantation (from 11.8 ± 0.9 tpm to -1.9 ± 0.4 tpm), showing the fastest recovery. With regard to the reinnervation of the lesioned striatum DA cells co-transplanted with SC HMW revealed a fiber density of 92.0 ± 1.3%, whereas the fiber density of the corresponding control group was only 63.0 ± 5.2%. FGF-2-mediated effects are more pronounced after co-transplantation with SC/DA cells mixed in one suspension at the same implantation side than in the side-by-side approach with a spatially and temporally separated transplantation of SC (day1) and DA-cells (day3).


In the present study a model of co-transplantation with genetically modified cells was established in the rat model of PD which might become a useful tool to further elucidate the close interactions between the different FGF-2 isoforms and DA neurons. Furthermore, the first demonstration of the presence of the 21kD/23kD FGF-2 isoforms in the nigrostriatal system and their potent neurotrophic in vivo activities, as shown in the present study, suggest (I) a physiological role of these proteins for dopaminergic neurons and (II) a restorative potential under normal as well as regenerative processes. We propose that administration of 21kD/23kD FGF-2 may be used to improve function in the rat Parkinson´s disease model. This may also help to further optimize current transplantation strategies to restore the DA system in patients with PD.