Fetal nondopaminergic neural implants in parkinsonian primates. Histochemical and behavioral studies.
Implantation of fetal dopamine-containing tissue into preformed cavities in the caudate nucleus of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian monkeys leads to behavioral recovery. Recovery may be related to two sources of dopamine: the grafted cells and/or the sprouted fibers from host dopaminergic neurons. The authors undertook this study to determine whether behavioral recovery requires release of dopamine by the implanted tissue, and to establish if nondopaminergic fetal central nervous system implants can induce sprouting of dopamine fibers in the primate brain and cause behavioral recovery. Rhesus monkeys with MPTP-induced hemiparkinsonism or full parkinsonism and a stable neurological deficit were used for this study. Cavities were created in the caudate nuclei anterior to the foramen of Monro via an open microsurgical approach. Fetal cerebellum or spinal cord was implanted into the preformed cavities of three monkeys. Control parkinsonian monkeys showed no recovery. However, implant-induced improvement was stable for up to 6 months after implantation. Sprouted dopaminergic fibers oriented from the ventral striatum and nucleus accumbens were found in the area of the tissue implant in the animals that received fetal grafts but were not present in the control monkeys. It is concluded that brain implants do not need to contain dopamine to induce functional recovery in MPTP-induced parkinsonian primates. Implant-induced and trophic factor-mediated dopaminergic sprouting by the host brain plays a role in the behavioral recovery and may well be responsible for the clinical improvement seen in parkinsonian patients after brain implants.
Bankiewicz
K S
KS
Laboratory of Central Nervous System Implantation, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
Plunkett
R J
RJ
Jacobowitz
D M
DM
Kopin
I J
IJ
Oldfield
E H
EH
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D016380:Brain Tissue Transplantation; D002421:Caudate Nucleus / Q000378:metabolism / Q000601:surgery*; D002531:Cerebellum / Q000378:metabolism / Q000637:transplantation*; D004298:Dopamine / Q000494:pharmacology*; D016332:Fetal Tissue Transplantation; D007150:Immunohistochemistry; D008253:Macaca mulatta; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology / Q000601:surgery*; D013116:Spinal Cord / Q000378:metabolism / Q000637:transplantation*; D014446:Tyrosine 3-Monooxygenase
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine