A primate model of Huntington's disease: functional neural transplantation and CT-guided stereotactic procedures.
In this article, we show that 1) computed tomographic (CT)-guided stereotactic infusion of an excitotoxin into the striatum of a nonhuman primate provides a useful neuropathologic and behavioral model for Huntington's disease. 2) High-resolution positron emission tomography (PET) can be used to image the decreased glucose utilization and the preservation of dopaminergic terminals in the lesioned striatum by using 2-fluoro-deoxy-D-glucose (2FDG) and N-(C-11)-methyl-2-beta-carbomethoxy-3-beta-phenyl tropane (CPT) as tracers. 3) Transplantation of cross-species striatal fetal tissue into the lesioned caudate-putamen reduces many of the abnormal motor movements and behavioral changes seen in the Huntington's disease primate model. 4) Graft rejection results in the return of the abnormal signs of the pregrafted state. These results indicate that treatment of the neuronal deficit in Huntington's disease can involve intervention at the local neuronal circuit level. CT-guided stereotactic implantation of cells that might protect or replace this defective circuitry may eventually provide an effective treatment for Huntington's disease.
Department of Neurology, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
J M
JM
Schumacher
P
P
Hantraye
A L
AL
Brownell
D
D
Riche
B K
BK
Madras
P D
PD
Davenport
M
M
Maziere
D R
DR
Elmaleh
G L
GL
Brownell
O
O
Isacson
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D016380:Brain Tissue Transplantation / Q000502:physiology; D002250:Carbon Radioisotopes; D002421:Caudate Nucleus / Q000473:pathology*; D003042:Cocaine / Q000031:analogs & derivatives / Q000378:metabolism; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D016332:Fetal Tissue Transplantation / Q000502:physiology; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006085:Graft Survival; D006816:Huntington Disease / Q000000981:diagnostic imaging / Q000601:surgery*; D007051:Ibotenic Acid; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009498:Neurotoxins; D010215:Papio; D011699:Putamen / Q000473:pathology*; D017378:Quinolinic Acid; D051381:Rats; D013238:Stereotaxic Techniques; D014055:Tomography, Emission-Computed; D014057:Tomography, X-Ray Computed; D014183:Transplantation, Heterologous
D002250:Carbon Radioisotopes; D009498:Neurotoxins; D019788:Fluorodeoxyglucose F18; D007051:Ibotenic Acid; C021278:troparil; D003847:Deoxyglucose; D017378:Quinolinic Acid; D003042:Cocaine; D005947:Glucose; D001058:Apomorphine