Glial Cell Line-Derived Neurotrophic Factor Improves Survival of Dopaminergic Neurons in Transplants of Fetal Ventral Mesencephalic Tissue

1998 ◽  
Vol 153 (2) ◽  
pp. 195-202 ◽  
Author(s):  
David M. Yurek
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Ventral Mesencephalic

Glial cell line-derived neurotrophic factor reverses toxin-induced injury to midbrain dopaminergic neurons in vivo

1994 ◽  
Vol 182 (1) ◽  
pp. 107-111 ◽  
Author(s):  
Barry J. Hoffer ◽  
Alex Hoffman ◽  
Kate Bowenkamp ◽  
Peter Huettl ◽  
John Hudson ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Midbrain Dopaminergic Neurons

Early transplantation of an encapsulated glial cell line—derived neurotrophic factor—producing cell demonstrating strong neuroprotective effects in a rat model of Parkinson disease

2005 ◽  
Vol 102 (1) ◽  
pp. 80-89 ◽  
Author(s):  
Takao Yasuhara ◽  
Tetsuro Shingo ◽  
Kenichiro Muraoka ◽  
Kazuki Kobayashi ◽  
Akira Takeuchi ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Cell Line ◽  
Glial Cell ◽  
Rat Model ◽  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Neuroprotective Effects ◽  
Content Type ◽  
Glial Proliferation ◽  
Fine Print

Object. Glial cell line—derived neurotrophic factor (GDNF) has been shown to confer neuroprotective effects on dopaminergic neurons. The authors investigated the effects of GDNF on 6-hydroxydopamine (6-OHDA)—treated dopaminergic neurons in vitro and in vivo. Methods. First, the authors examined how 1, 10, or 100 ng/ml of GDNF, administered to cells 24 hours before, simultaneously with, or 2 or 4 hours after 6-OHDA was added, affected dopaminergic neurons. In a primary culture of E14 murine ventral mesencephalic neurons, earlier treatment with the higher dosage of GDNF suppressed 6-OHDA—induced loss of dopaminergic neurons better than later treatment. Next, the authors examined whether continuous infusion of GDNF at earlier time points would demonstrate a greater neuroprotective effect in a rat model of Parkinson disease (PD). They established a human GDNF-secreting cell line, called BHK-GDNF, and encapsulated the cells into hollow fibers. The encapsulated cells were unilaterally implanted into the striatum of adult rats 1 week before; simultaneously with; or 1, 2, or 4 weeks after 6-OHDA was given to induce lesions of the same striatum. With the earlier transplantation of a BHK-GDNF capsule, there was a significant reduction in the number of amphetamine-induced rotations displayed by the animals. Rats that had received earlier implantation of BHK-GDNF capsules displayed more tyrosine hydroxylase—positive neurons in the substantia nigra pars compacta and a tendency for glial proliferation in the striatum. Conclusions. These neuroprotective effects may be related to glial proliferation and signaling via the GDNF receptor α1. The results of this study support a role for this grafting technique in the treatment of PD.

Grafting of Nigral Tissue Hibernated with Tirilazad Mesylate and Glial Cell Line-Derived Neurotrophic Factor

2000 ◽  
Vol 9 (5) ◽  
pp. 577-584 ◽  
Author(s):  
Åsa Petersén ◽  
Oskar Hansson ◽  
Mia Emgård ◽  
Patrik Brundin
Keyword(s):  
Cell Suspension ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Limiting Factor ◽  
Tissue Storage ◽  
Significant Difference ◽  
Tirilazad Mesylate ◽  
Clinical Transplantation

Transplantation of embryonic ventral mesencephalon is a potential therapy for patients with Parkinson's disease. As only around 5–10% of embryonic dopaminergic neurons survive grafting into the adult striatum, it is considered necessary to use multiple donor embryos. To increase the survival of the grafted dopaminergic neurons, the clinical transplantation program in Lund currently employs the lipid peroxidation inhibitor, tirilazad mesylate, in all solutions used during tissue storage, preparation, and transplantation. However, the difficulty in obtaining a sufficient number of donor embryos still remains an important limiting factor for the clinical application of neural transplantation. In many clinical transplantation programs, it would be a great advantage if human nigral donor tissue could be stored for at least 1 week. This study was performed in order to investigate whether storage of embryonic tissue at 4°C for 8 days can be applied clinically without creating a need to increase the number of donors. We compared the survival of freshly grafted rat nigral tissue, prepared according to the clinical protocol, with tissue transplanted after hibernation. Thus, in all groups tirilazad mesylate was omnipresent. One group of rats was implanted with fresh tissue and three groups with hibernated tissue with or without addition of glial cell line-derived neurotrophic factor (GDNF) in the hibernation medium and/or the final cell suspension. Earlier studies have suggested that GDNF improves the survival of hibernated nigral transplants. We found no statistically significant difference between the groups regarding graft survival after 3 weeks. However, there was a nonsignificant trend for fewer surviving dopaminergic neurons in grafts from hibernated tissue compared to fresh controls. Furthermore, we show that the addition of GDNF to the hibernation medium and/or to the final cell suspension does not significantly increase the survival of the dopaminergic neurons.

scholarly journals Glial Cell Line-Derived Neurotrophic Factor Family Members Reduce Microglial Activation via Inhibiting p38MAPKs-Mediated Inflammatory Responses

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Uta Rickert ◽  
Steffen Grampp ◽  
Henrik Wilms ◽  
Jessica Spreu ◽  
Friederike Knerlich-Lukoschus ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Microglial Activation ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Target Cells ◽  
Receptor System

Previous studies have shown that glial cell line-derived neurotrophic factor (GDNF) family ligands (GFL) are potent survival factors for dopaminergic neurons and motoneurons with therapeutic potential for Parkinson’s disease. However, little is known about direct influences of the GFL on microglia function, which are known to express part of the GDNF receptor system. Using RT-PCR and immunohistochemistrym we investigated the expression of the GDNF family receptor alpha 1 (GFR alpha) and the coreceptor transmembrane receptor tyrosine kinase (RET) in rat microglia in vitro as well as the effect of GFL on the expression of proinflammatory molecules in LPS activated microglia. We could show that GFL are able to regulate microglia functions and suggest that part of the well known neuroprotective action may be related to the suppression of microglial activation. We further elucidated the functional significance and pathophysiological implications of these findings and demonstrate that microglia are target cells of members of the GFL (GDNF and the structurally related neurotrophic factors neurturin (NRTN), artemin (ARTN), and persephin (PSPN)).

scholarly journals Glial cell line-derived neurotrophic factor protects midbrain dopaminergic neurons against lipopolysaccharide neurotoxicity

2010 ◽  
Vol 225 (1-2) ◽  
pp. 43-51 ◽  
Author(s):  
Bin Xing ◽  
Tao Xin ◽  
Lingling Zhao ◽  
Randy L. Hunter ◽  
Yan Chen ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Midbrain Dopaminergic Neurons
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