Pharmacological MRI (phMRI) monitoring of treatment in hemiparkinsonian rhesus monkeys.
There is a great need for the development of noninvasive, highly sensitive, and widely available imaging methods that can potentially be used to longitudinally monitor treatment of Parkinson's disease (PD). Here we report the monitoring of GDNF-induced functional changes of the basal ganglia in hemiparkinsonian monkeys via pharmacological MRI measuring the blood oxygenation level-dependent (BOLD) response to a direct dopamine agonist (apomorphine, APO). After testing BOLD responsiveness to APO in their normal state, two additional scans were taken with the same dose of APO stimulation after induced parkinsonism. Then all animals were chronically treated with GDNF for 18 weeks by a programmable pump and catheter system. The catheter was surgically implanted into the right putamen and connected to the pump via flexible polyurethane tubing, phMRI scans were taken at both 6 and 18 weeks while they received 22.5 microg of GDNF per day. In addition, behavioral changes were monitored throughout the entire study. The primary finding of this study was that APO-evoked activations in the DA denervated putamen were attenuated by the chronic intraputamenal infusion of GDNF accompanied by improvements of parkinsonian features, movement speed, and APO-induced rotation compared to data collected before the chronic GDNF treatment. The results suggest that phMRI methods in combination with administration of a selective DA agonist may be useful for monitoring neurorestorative therapies in PD patients in the future.
Department of Anatomy & Neurobiology, College of Medicine, University of Kentucky, Lexington, KY 40536-0098, USA.
Liming
L
Luan
Feng
F
Ding
Yi
Y
Ai
Anders
A
Andersen
Peter
P
Hardy
Eric
E
Forman
Greg A
GA
Gerhardt
Don M
DM
Gash
Richard
R
Grondin
Zhiming
Z
Zhang
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001058:Apomorphine / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging / Q000379:methods; D009498:Neurotoxins / Q000494:pharmacology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology
D000978:Antiparkinson Agents; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009498:Neurotoxins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D001058:Apomorphine