Intraventricular infusion of basic fibroblast growth factor (bFGF) in the MPTP-treated common marmoset.
Basic fibroblast growth factor (bFGF) prevents damage to the nigrostriatal system in rodents. We now report the effects of bFGF administered by intraventricular infusion to adult common marmosets (Callithrix jacchus) previously rendered parkinsonian by the administration of 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Infusion commenced 10 weeks after MPTP treatment and the animals received bFGF in low (1.8 micrograms/l), medium (18 micrograms/l), or high (180 micrograms/l) doses over a 28-day period. At weekly intervals, automated activity measurements, behavioral disability scoring, and videotape analyses were made. There was no improvement in the motor deficits exhibited by MPTP-treated common marmosets receiving bFGF infusion compared to vehicle-treated controls. Three of five high dose animals showed neurological impairment prior to the end of the study. No significant differences were found between control and bFGF-infused MPTP-treated common marmosets with respect to nigral tyrosine hydroxylase immunoreactive cell counts and striatal [3H]mazindol binding. All high dose animals showed hydrocephalus which was also observed in four other animals receiving bFGF. Histological examination revealed proliferation of the choroid plexus and ependyma which was most marked in the high dose animals. Adverse effects, in the form of hydrocephalus and neurological deterioration, were presumably secondary to an ependymal and choroid plexus reaction induced by bFGF.
Pearce
R K
RK
Neurodegenerative Diseases Research Centre, King's College, London, UK.
Collins
P
P
Jenner
P
P
Emmett
C
C
Marsden
C D
CD
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology; D001923:Brain Chemistry / Q000187:drug effects; D002144:Callithrix; D002452:Cell Count; D015259:Dopamine Agents / Q000494:pharmacology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006849:Hydrocephalus / Q000139:chemically induced / Q000473:pathology; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015259:Dopamine Agents; D005904:Glial Fibrillary Acidic Protein; D016222:Fibroblast Growth Factor 2; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase