Basic fibroblast growth factor promotes the survival of embryonic ventral mesencephalic dopaminergic neurons--II. Effects on nigral transplants in vivo.
The clinical potential of transplants of fetal dopaminergic neurons is limited by the fact that the percentage of cells surviving in such grafts is in general quite low. This report investigates the use of basic fibroblast growth factor administration (given either as a pretreatment or by repeated intrastriatal infusions) to promote the survival and behavioural efficacy of embryonic dopamine-rich nigral transplants in rats. Pretreatment of the graft tissue by brief incubation with basic fibroblast growth factor increased the survival of tyrosine hydroxylase-immunoreactive (presumed dopaminergic) neurons in the grafts in comparison to control grafts, and accelerated the recovery in the transplanted animals in tests of drug-induced rotational asymmetry. However, the clear advantage seen in the rotation test conducted three weeks after transplantation had disappeared by nine weeks. The moderate effects of pretreatment were markedly enhanced by repeated intrastriatal infusion of basic fibroblast growth factor into the host animals over 20 days following transplantation. This resulted in > 100% increase in the number of dopaminergic neurons surviving in the grafts, and was accompanied by a significantly greater recovery of the rats' rotational asymmetries which persisted over the full nine weeks of testing. However, the repeated intracerebral infusions induced an inflammatory reaction in the striatum, and the associated trauma both complicates the interpretation of the mechanism of observed recovery and compromises the utility of this route of basic fibroblast growth factor administration for promoting graft survival.
Mayer
E
E
MRC Cambridge Centre for Brain Repair, University of Cambridge, U.K.
Fawcett
J W
JW
Dunnett
S B
SB
D000818:Animals; D016380:Brain Tissue Transplantation; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D016332:Fetal Tissue Transplantation; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008636:Mesencephalon / Q000187:drug effects* / Q000196:embryology; D016627:Oxidopamine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000637:transplantation*
D016222:Fibroblast Growth Factor 2; D016627:Oxidopamine; D004298:Dopamine