Additive effect of glial cell line-derived neurotrophic factor and neurotrophin-4/5 on rat fetal nigral explant cultures
Section snippets
Preparation of cultures
Under deep pentobarbital anesthesia, embryos (embryonic day (E) 14) were removed by Cesarean section from pregnant Sprague–Dawley rats (BRL Biological Research, Füllinsdorf, Switzerland) and killed by decapitation (all efforts were made to minimize both the suffering and number of animals used). From the isolated brains the ventral mesencephali were dissected out according to standard techniques (Dunnett and Björklund, 1992), and grown as FFRT cultures (Spenger et al., 1994). In brief, each
Effect of growth factor treatment on culture volume and protein content
Cultures from all experimental groups showed a steady increase in volume during the culture period as observed by routine inspection. At day 4, the cultured mesencephalic tissue had formed small spheres, and at day 8 the culture diameter ranged between 0.9 and 1.5 mm. At that time-point, cultures treated with NT-4/5 or GDNF+NT-4/5 were significantly larger than controls [59% (P<0.05) and 101% (P<0.01), respectively], whereas GDNF-treated cultures were not different from controls (P>0.05; Table 1
Discussion
Intracerebral transplantation into severely diseased parkinsonian patients has provided promising results in several clinical trials, but suboptimal survival or differentiation of grafted dopaminergic neurons as well as ethical concerns and the limited availability of embryonic human donor tissue prevent a more widespread application as described in several papers (Lindvall et al., 1990, Freed et al., 1992, Freeman et al., 1995, Olanow et al., 1996, Kordower et al., 1998, Tabbal et al., 1998,
Acknowledgements
The expert technical assistance of Sandra Krebs, Tanja Bosnjak, and Inge Holst is gratefully acknowledged. We also wish to express our gratitude to Dr. Christian Spenger, Stockholm, Sweden for help with the HPLC analysis, Dr. Lars Korsholm, Odense, Denmark for statistical advice, and Dr. Anthony Castro, Marywood, USA for critical comments on the manuscript. This research was supported by the Swiss National Science Foundation (Grant No. 31-52947.97), Desirée and Niels Ydes Foundation, the Danish
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