Effects of biologically delivered NGF, BDNF and bFGF on striatal excitotoxic lesions.
Immortalized rat fibroblasts, genetically altered to secrete NGF, BDNF, and bFGF, were implanted in rat brain near the striatum 7 days before striatal infusion of excitotoxic quantities of an NMDA-receptor agonist. Analysis of striatal damage 7 days after lesioning revealed that implantation of NGF-secreting cells reduced the size of the excitotoxic lesions by more than 80% when compared with control cells, while implanting of bFGF-secreting cells caused a 30% decrease in excitotoxic lesion size. BDNF-secreting fibroblasts caused no protective sparing in the striatum in this lesion model. This finding shows that biological delivery of NGF and bFGF by grafting of genetically altered cells protects against glutamate toxicity in the adult striatum while grafting of BDNF-producing cells does not. Such observations begin to define a spectrum of neurotrophic agents able to mitigate the cell loss seen in neurodegeneration.
Frim
D M
DM
Neuroregeneration Laboratory, McLean Hospital, Belmont, MA.
Uhler
T A
TA
Short
M P
MP
Ezzedine
Z D
ZD
Klagsbrun
M
M
Breakefield
X O
XO
Isacson
O
O
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D002460:Cell Line; D003342:Corpus Striatum / Q000187:drug effects*; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology*; D005347:Fibroblasts / Q000637:transplantation; D009410:Nerve Degeneration / Q000187:drug effects*; D009412:Nerve Fibers / Q000737:chemistry; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016222:Fibroblast Growth Factor 2; D014446:Tyrosine 3-Monooxygenase; D000109:Acetylcholine