Pharmacological MRI (phMRI) Monitoring of Treatment in Hemiparkinsonian Rhesus Monkeys

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Abstract:

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 g 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.

Keywords: Apomorphine; Catheter; GDNF; MPTP; Parkinson's disease; Pump; Putamen; Rhesus monkey; phMRI

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096368908784423319

Affiliations: 1: Department of Anatomy & Neurobiology, College of Medicine, University of Kentucky, Lexington, KY, USA, Department of Neurosurgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, PR China 2: Department of Anatomy & Neurobiology, College of Medicine, University of Kentucky, Lexington, KY, USA, †Department of Neurosurgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, PR China 3: Department of Anatomy & Neurobiology, College of Medicine, University of Kentucky, Lexington, KY, USA, Morris K. Udall Parkinson's Disease Research Center of Excellence, College of Medicine, University of Kentucky, Lexington, KY, USA 4: Magnetic Resonance Imaging and Spectroscopy Center, College of Medicine, University of Kentucky, Lexington, KY, USA 5: Department of Anatomy & Neurobiology, College of Medicine, University of Kentucky, Lexington, KY, USA

Publication date: April 1, 2008

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