Basal ganglia lesions after MPTP administration in rhesus monkeys
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...
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| Published in | Neurobiology of disease Vol. 23; no. 2; pp. 281 - 289 |
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| Main Authors | , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.08.2006
Elsevier |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0969-9961 1095-953X |
| DOI | 10.1016/j.nbd.2006.03.010 |
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| Abstract | 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. |
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| AbstractList | 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. 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.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. |
| Author | Roitberg, B. Emborg, M.E. Ma, Y. Ambarish, P. Leestma, J.E. Eidelberg, D. Konecny, T. Kordower, J.H. Moirano, J. Schafernak, K.T. Moirano, M. Evans, M. Mangubat, E. Holden, J. |
| Author_xml | – sequence: 1 givenname: M.E. surname: Emborg fullname: Emborg, M.E. email: emborg@primate.wisc.edu organization: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA – sequence: 2 givenname: J. surname: Moirano fullname: Moirano, J. organization: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA – sequence: 3 givenname: K.T. surname: Schafernak fullname: Schafernak, K.T. organization: Department of Pathology, Northwestern University, Chicago, IL 60611, USA – sequence: 4 givenname: M. surname: Moirano fullname: Moirano, M. organization: Department of Neurological Sciences, Rush University, Chicago, IL 60612, USA – sequence: 5 givenname: M. surname: Evans fullname: Evans, M. organization: Department of Neurological Sciences, Rush University, Chicago, IL 60612, USA – sequence: 6 givenname: T. surname: Konecny fullname: Konecny, T. organization: Department of Neurosurgery, University of Illinois at Chicago, Chicago, IL 60612, USA – sequence: 7 givenname: B. surname: Roitberg fullname: Roitberg, B. organization: Department of Neurosurgery, University of Illinois at Chicago, Chicago, IL 60612, USA – sequence: 8 givenname: P. surname: Ambarish fullname: Ambarish, P. organization: Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60612, USA – sequence: 9 givenname: E. surname: Mangubat fullname: Mangubat, E. organization: Department of Neurosurgery, University of Illinois at Chicago, Chicago, IL 60612, USA – sequence: 10 givenname: Y. surname: Ma fullname: Ma, Y. organization: Center for Neurosciences, Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY 11030, USA – sequence: 11 givenname: D. surname: Eidelberg fullname: Eidelberg, D. organization: Center for Neurosciences, Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY 11030, USA – sequence: 12 givenname: J. surname: Holden fullname: Holden, J. organization: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA – sequence: 13 givenname: J.H. surname: Kordower fullname: Kordower, J.H. organization: Department of Neurological Sciences, Rush University, Chicago, IL 60612, USA – sequence: 14 givenname: J.E. surname: Leestma fullname: Leestma, J.E. organization: Department of Pathology, Children's Memorial Hospital, Chicago, IL 60611, USA |
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| Keywords | Striatum Stroke Parkinson's disease Nonhuman primates Globus pallidus Aging MPTP Gene therapy Necrosis |
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| Title | Basal ganglia lesions after MPTP administration in rhesus monkeys |
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