Journal
NEUROBIOLOGY OF DISEASE
Volume 23, Issue 2, Pages 281-289Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2006.03.010
Keywords
MPTP; nonhuman primates; globus pallidus; striatum; necrosis; aging; stroke; Parkinson's disease; gene therapy
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Funding
- NCRR NIH HHS [5P51RR000167] Funding Source: Medline
- NINDS NIH HHS [R01-NS40578] Funding Source: Medline
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In monkeys, intracarotid infusion of a single low dose of MPTP reliably induces a hemiparkinsonian syndrome that is stable over time. This model has been widely used to assess novel anti-parkinsonian therapies. Here, we report the exceptional finding of severe necrotic lesions that were observed in the basal ganglia (but not in the substantia nigra) of monkeys that received a single intracarotid injection of MPTP followed by gene therapy treatments. Although extensive unilateral dopaminergic nigrostriatal loss was found in all the animals, partial behavioral recovery was observed in the subjects that presented pallidal necrotic lesions. This report discusses possible causes and effects of the necrotic lesions and their locations and the value of the intracarotid MPTP model. Testing novel therapies in monkey models has become an essential step before clinical trials. These results indicate that evaluation of any treatment should consider possible confounding factors that may affect the results. (c) 2006 Elsevier Inc. All rights reserved.
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