The Experts below are selected from a list of 198 Experts worldwide ranked by ideXlab platform
J W Langston - One of the best experts on this subject based on the ideXlab platform.
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Investigating levodopa-induced dyskinesias in the Parkinsonian Primate
Annals of Neurology, 2000Co-Authors: J W Langston, Maryka Quik, Giselle M. Petzinger, Michael W. Jakowec, Donato A. Di MonteAbstract:Research into the cause of dyskinesias arising from levodopa treatment has been vexingly limited, partly due to the lack of an inexpensive and widely available animal model. Rodents do not develop levodopa-induced dyskinesias in a clinically recognizable form. However, nonhuman primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism readily develop levodopa-induced dyskinesias that are virtually indistinguishable from those seen in patients with Parkinson's disease. We have developed and validated a five-point Global Primate Dyskinesia Rating Scale to accurately measure these dyskinesias. Monkeys with MPTP-induced Parkinsonism were then investigated to evaluate the relationship between dyskinesias, Parkinsonism and severity of the nigrostriatal lesion. All parkinsonian animals were responsive to levodopa, and developed dyskinesias within 2-3 days of levodopa administration. Monkeys treated with only a single injection of MPTP also developed dyskinesias, even though they were not parkinsonian. It would appear that there is a different threshold of striatal dopamine depletion for Parkinsonism and dyskinesias in the monkey. Finally, three hypotheses, put forward to explain the genesis of dyskinesias, are reviewed, and various experimental approaches suggested for each.
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evidence of active nerve cell degeneration in the substantia nigra of humans years after 1 methyl 4 phenyl 1 2 3 6 tetrahydropyridine exposure
Annals of Neurology, 1999Co-Authors: J W Langston, Lysia S Forno, J Tetrud, Alexander G Reeves, J A Kaplan, D KarlukAbstract:This report provides the first detailed neuropathological study of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism in humans. All 3 subjects self-administered the drug under the impression it was "synthetic heroin" and subsequently developed severe and unremitting Parkinsonism, which was L-dopa responsive, at least in the earlier stages of illness. Survival times ranged from 3 to 16 years. Neuropathological examination revealed moderate to severe depletion of pigmented nerve cells in the substantia nigra in each case. Lewy bodies were not present. In Patients 1 and 2, there was gliosis and clustering of microglia around nerve cells. Patient 3 had a similar picture and also showed large amounts of extraneuronal melanin. These findings are indicative of active, ongoing nerve cell loss, suggesting that a time-limited insult to the nigrostriatal system can set in motion a self-perpetuating process of neurodegeneration. Although the mechanism by which this occurs is far from clear, the precedent set by the cases could have broad implications for human neurodegenerative disease.
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Long latency postural reflexes are under supraspinal dopaminergic control
Movement disorders : official journal of the Movement Disorder Society, 1995Co-Authors: B.r. Bloem, J W Langston, D J Beckley, J G Van Dijk, J.p.p. Van Vugt, M. P. Remler, R A RoosAbstract:Scaling of posturally stabilizing long latency (LL) reflexes in tibialis anterior muscles induced by "toe-up" rotational perturbations is abnormal in standing patients with Parkinson's disease. To investigate the contribution of dopaminergic pathways to abnormal scaling, we studied LL reflexes in 22 patients with selective hypodopaminergic syndromes: 10 psychiatric patients taking chronic neuroleptic medication (7 with mild Parkinsonism), 8 patients with young-onset Parkinson's disease, and 4 patients with MPTP-induced Parkinsonism. Results were compared with those of 10 healthy controls. Stimuli consisted of (a) 10 serial (predictable) perturbations of 4 degrees amplitude, (b) 10 serial (predictable) perturbations of 10 degrees amplitude, and (c) 20 randomly mixed (unpredictable) perturbations of either 4 or 10 degrees amplitude. In normal subjects, LL reflex amplitudes were adapted to match predictable variations in stimulus size, whereas under unpredictable conditions a "default" response emerged that anticipated the 10 degrees perturbation. LL reflex scaling under predictable conditions was intact in patients with neuroleptic-induced Parkinsonism and young-onset Parkinson's disease, but the large default LL response under unpredictable conditions was absent. In patients with MPTP-induced Parkinsonism, LL reflex scaling was absent during both predictable and unpredictable conditions. We conclude that abnormal scaling of posturally stabilizing LL reflexes is related to decreased supraspinal dopaminergic influence.
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Medium latency stretch reflexes in young-onset Parkinson's disease and MPTP-induced Parkinsonism.
Journal of the Neurological Sciences, 1994Co-Authors: B R Bloem, J W Langston, D J Beckley, J G Van Dijk, A H Zwinderman, M P Remler, R A RoosAbstract:Abstract It is still unclear why components of the phasic stretch reflex are increased in Parkinson's disease (PD). To study the role of aging, we assessed medium latency (ML) stretch reflexes in 19 Parkinson patients (8 with young-onset PD, 11 with late-onset PD) and 23 normal subjects (10 young, 13 old). To assess the contribution of supraspinal dopaminergic influences, we also studied 5 young parkinsonian patients with a selective central dopamine deficiency induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). ML responses were recorded from the medial gastrocnemius muscle which was stretched by 4° toe-up rotations of a platform upon which subjects were standing. ML responses were significantly enhanced in late-onset patients compared with older controls. In contrast, ML responses did not differ between young-onset patients and young controls. This observation could be attributed to the significantly different influence of age on ML-amplitudes in patients and controls. Thus, ML-amplitudes declined with age in controls, whereas they increased with age in PD possibly because older patients were more severely affected than younger patients. Thus, the difference between young-onset and late-onset PD seems to be related to the opposite effects of increasing age and disease severity in patients and controls. ML-amplitudes did not differ between patients with MPTP-induced Parkinsonism, patients with young-onset PD and controls, suggesting that supraspinal dopaminergic systems are not critically involved in control of ML responses. This result also indicates that the severity effect in PD may be related to disruption of non-dopaminergic pathways which occurs in late-onset, but not young-onset patients. In conclusion, we postulate that lesions in non-dopaminergic systems in older Parkinson patients contribute to enhancement of ML responses, and possibly other late occurring stretch reflexes as well.
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Medium latency stretch reflexes in young-onset Parkinson's disease and MPTP-induced Parkinsonism.
Journal of the neurological sciences, 1994Co-Authors: B R Bloem, J W Langston, D J Beckley, J G Van Dijk, A H Zwinderman, M P Remler, R A RoosAbstract:It is still unclear why components of the phasic stretch reflex are increased in Parkinson's disease (PD). To study the role of aging, we assessed medium latency (ML) stretch reflexes in 19 Parkinson patients (8 with young-onset PD, 11 with late-onset PD) and 23 normal subjects (10 young, 13 old). To assess the contribution of supraspinal dopaminergic influences, we also studied 5 young parkinsonian patients with a selective central dopamine deficiency induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). ML responses were recorded from the medial gastrocnemius muscle which was stretched by 4 degrees toe-up rotations of a platform upon which subjects were standing. ML responses were significantly enhanced in late-onset patients compared with older controls. In contrast, ML responses did not differ between young-onset patients and young controls. This observation could be attributed to the significantly different influence of age on ML-amplitudes in patients and controls. Thus, ML-amplitudes declined with age in controls, whereas they increased with age in PD possibly because older patients were more severely affected than younger patients. Thus, the difference between young-onset and late-onset PD seems to be related to the opposite effects of increasing age and disease severity in patients and controls. ML-amplitudes did not differ between patients with MPTP-induced Parkinsonism, patients with young-onset PD and controls, suggesting that supraspinal dopaminergic systems are not critically involved in control of ML responses. This result also indicates that the severity effect in PD may be related to disruption of non-dopaminergic pathways which occurs in late-onset, but not young-onset patients.(ABSTRACT TRUNCATED AT 250 WORDS)
R A Roos - One of the best experts on this subject based on the ideXlab platform.
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Long latency postural reflexes are under supraspinal dopaminergic control
Movement disorders : official journal of the Movement Disorder Society, 1995Co-Authors: B.r. Bloem, J W Langston, D J Beckley, J G Van Dijk, J.p.p. Van Vugt, M. P. Remler, R A RoosAbstract:Scaling of posturally stabilizing long latency (LL) reflexes in tibialis anterior muscles induced by "toe-up" rotational perturbations is abnormal in standing patients with Parkinson's disease. To investigate the contribution of dopaminergic pathways to abnormal scaling, we studied LL reflexes in 22 patients with selective hypodopaminergic syndromes: 10 psychiatric patients taking chronic neuroleptic medication (7 with mild Parkinsonism), 8 patients with young-onset Parkinson's disease, and 4 patients with MPTP-induced Parkinsonism. Results were compared with those of 10 healthy controls. Stimuli consisted of (a) 10 serial (predictable) perturbations of 4 degrees amplitude, (b) 10 serial (predictable) perturbations of 10 degrees amplitude, and (c) 20 randomly mixed (unpredictable) perturbations of either 4 or 10 degrees amplitude. In normal subjects, LL reflex amplitudes were adapted to match predictable variations in stimulus size, whereas under unpredictable conditions a "default" response emerged that anticipated the 10 degrees perturbation. LL reflex scaling under predictable conditions was intact in patients with neuroleptic-induced Parkinsonism and young-onset Parkinson's disease, but the large default LL response under unpredictable conditions was absent. In patients with MPTP-induced Parkinsonism, LL reflex scaling was absent during both predictable and unpredictable conditions. We conclude that abnormal scaling of posturally stabilizing LL reflexes is related to decreased supraspinal dopaminergic influence.
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Medium latency stretch reflexes in young-onset Parkinson's disease and MPTP-induced Parkinsonism.
Journal of the Neurological Sciences, 1994Co-Authors: B R Bloem, J W Langston, D J Beckley, J G Van Dijk, A H Zwinderman, M P Remler, R A RoosAbstract:Abstract It is still unclear why components of the phasic stretch reflex are increased in Parkinson's disease (PD). To study the role of aging, we assessed medium latency (ML) stretch reflexes in 19 Parkinson patients (8 with young-onset PD, 11 with late-onset PD) and 23 normal subjects (10 young, 13 old). To assess the contribution of supraspinal dopaminergic influences, we also studied 5 young parkinsonian patients with a selective central dopamine deficiency induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). ML responses were recorded from the medial gastrocnemius muscle which was stretched by 4° toe-up rotations of a platform upon which subjects were standing. ML responses were significantly enhanced in late-onset patients compared with older controls. In contrast, ML responses did not differ between young-onset patients and young controls. This observation could be attributed to the significantly different influence of age on ML-amplitudes in patients and controls. Thus, ML-amplitudes declined with age in controls, whereas they increased with age in PD possibly because older patients were more severely affected than younger patients. Thus, the difference between young-onset and late-onset PD seems to be related to the opposite effects of increasing age and disease severity in patients and controls. ML-amplitudes did not differ between patients with MPTP-induced Parkinsonism, patients with young-onset PD and controls, suggesting that supraspinal dopaminergic systems are not critically involved in control of ML responses. This result also indicates that the severity effect in PD may be related to disruption of non-dopaminergic pathways which occurs in late-onset, but not young-onset patients. In conclusion, we postulate that lesions in non-dopaminergic systems in older Parkinson patients contribute to enhancement of ML responses, and possibly other late occurring stretch reflexes as well.
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Medium latency stretch reflexes in young-onset Parkinson's disease and MPTP-induced Parkinsonism.
Journal of the neurological sciences, 1994Co-Authors: B R Bloem, J W Langston, D J Beckley, J G Van Dijk, A H Zwinderman, M P Remler, R A RoosAbstract:It is still unclear why components of the phasic stretch reflex are increased in Parkinson's disease (PD). To study the role of aging, we assessed medium latency (ML) stretch reflexes in 19 Parkinson patients (8 with young-onset PD, 11 with late-onset PD) and 23 normal subjects (10 young, 13 old). To assess the contribution of supraspinal dopaminergic influences, we also studied 5 young parkinsonian patients with a selective central dopamine deficiency induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). ML responses were recorded from the medial gastrocnemius muscle which was stretched by 4 degrees toe-up rotations of a platform upon which subjects were standing. ML responses were significantly enhanced in late-onset patients compared with older controls. In contrast, ML responses did not differ between young-onset patients and young controls. This observation could be attributed to the significantly different influence of age on ML-amplitudes in patients and controls. Thus, ML-amplitudes declined with age in controls, whereas they increased with age in PD possibly because older patients were more severely affected than younger patients. Thus, the difference between young-onset and late-onset PD seems to be related to the opposite effects of increasing age and disease severity in patients and controls. ML-amplitudes did not differ between patients with MPTP-induced Parkinsonism, patients with young-onset PD and controls, suggesting that supraspinal dopaminergic systems are not critically involved in control of ML responses. This result also indicates that the severity effect in PD may be related to disruption of non-dopaminergic pathways which occurs in late-onset, but not young-onset patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Xiaojiang Sun - One of the best experts on this subject based on the ideXlab platform.
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Therapeutic Effects of Rapamycin on MPTP-induced Parkinsonism in Mice
Neurochemical research, 2012Co-Authors: Kangyong Liu, Nan Shi, Yinyi Sun, Ting Zhang, Xiaojiang SunAbstract:In neurodegenerative disorders such as Parkinson's disease (PD), autophagy is implicated in the process of dopaminergic neuron cell death. The α-synuclein protein is a major component of Lewy bodies and Lewy neurites, and mutations in α-synuclein have been implicated in the etiology of familial PD. The current work investigates the mechanisms underlying the therapeutic effects of the autophagy-stimulating antibiotic rapamycin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Male C57BL/6 mice were treated with intravenous rapamycin or saline control for 7 days following MPTP administration. Immunohistochemistry and western blotting were used to detect alterations in the expression of PD biomarkers, including tyrosine hydroxylase (TH), and the level of autophagy was evaluated by the detection of both microtubule-associated protein light chain 3 (LC3) and α-Synuclein cleavage. In addition, levels of monoamine neurotransmitters were measured in the striatum using high performance liquid chromatography (HPLC). Immunohistochemistry using antibodies against TH indicated that the number of dopaminergic neurons in the substantia nigra following MPTP treatment was significantly higher in rapamycin-treated mice compared with saline-treated controls (p < 0.01). Levels of TH expression in the striatum were similar between the groups. α-synuclein Immunoreactivity was significantly decreased in rapamycin-treated mice compared with controls (p < 0.01). Immunoreactivity for LC3, however, was significantly higher in the rapamycin-treated animals than controls (p < 0.01). The concentrations of both striatal dopamine, and the dopamine metabolite DOPAC, were significantly decreased in both MPTP-treated groups compared with untreated controls. The loss of DOPAC was less severe in rapamycin-treated mice compared with saline-treated mice (p < 0.01) following MPTP treatment. These results demonstrate that treatment with rapamycin is able to prevent the loss of TH-positive neurons and to ameliorate the loss of DOPAC following MPTP treatment, likely via activation of autophagy/lysosome pathways. Thus, further investigation into the effectiveness of rapamycin administration in the treatment of PD is warranted.
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WITHDRAWN: Therapeutic effects of rapamycin on MPTP-induced Parkinsonism in mice
Neurochemistry international, 2011Co-Authors: Kangyong Liu, Ting Zhang, Chun-feng Liu, Liwei Shen, Jijun Shi, Yunjiao Zhou, Ling Zhou, Xiaojiang SunAbstract:This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
B R Bloem - One of the best experts on this subject based on the ideXlab platform.
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Medium latency stretch reflexes in young-onset Parkinson's disease and MPTP-induced Parkinsonism.
Journal of the Neurological Sciences, 1994Co-Authors: B R Bloem, J W Langston, D J Beckley, J G Van Dijk, A H Zwinderman, M P Remler, R A RoosAbstract:Abstract It is still unclear why components of the phasic stretch reflex are increased in Parkinson's disease (PD). To study the role of aging, we assessed medium latency (ML) stretch reflexes in 19 Parkinson patients (8 with young-onset PD, 11 with late-onset PD) and 23 normal subjects (10 young, 13 old). To assess the contribution of supraspinal dopaminergic influences, we also studied 5 young parkinsonian patients with a selective central dopamine deficiency induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). ML responses were recorded from the medial gastrocnemius muscle which was stretched by 4° toe-up rotations of a platform upon which subjects were standing. ML responses were significantly enhanced in late-onset patients compared with older controls. In contrast, ML responses did not differ between young-onset patients and young controls. This observation could be attributed to the significantly different influence of age on ML-amplitudes in patients and controls. Thus, ML-amplitudes declined with age in controls, whereas they increased with age in PD possibly because older patients were more severely affected than younger patients. Thus, the difference between young-onset and late-onset PD seems to be related to the opposite effects of increasing age and disease severity in patients and controls. ML-amplitudes did not differ between patients with MPTP-induced Parkinsonism, patients with young-onset PD and controls, suggesting that supraspinal dopaminergic systems are not critically involved in control of ML responses. This result also indicates that the severity effect in PD may be related to disruption of non-dopaminergic pathways which occurs in late-onset, but not young-onset patients. In conclusion, we postulate that lesions in non-dopaminergic systems in older Parkinson patients contribute to enhancement of ML responses, and possibly other late occurring stretch reflexes as well.
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Medium latency stretch reflexes in young-onset Parkinson's disease and MPTP-induced Parkinsonism.
Journal of the neurological sciences, 1994Co-Authors: B R Bloem, J W Langston, D J Beckley, J G Van Dijk, A H Zwinderman, M P Remler, R A RoosAbstract:It is still unclear why components of the phasic stretch reflex are increased in Parkinson's disease (PD). To study the role of aging, we assessed medium latency (ML) stretch reflexes in 19 Parkinson patients (8 with young-onset PD, 11 with late-onset PD) and 23 normal subjects (10 young, 13 old). To assess the contribution of supraspinal dopaminergic influences, we also studied 5 young parkinsonian patients with a selective central dopamine deficiency induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). ML responses were recorded from the medial gastrocnemius muscle which was stretched by 4 degrees toe-up rotations of a platform upon which subjects were standing. ML responses were significantly enhanced in late-onset patients compared with older controls. In contrast, ML responses did not differ between young-onset patients and young controls. This observation could be attributed to the significantly different influence of age on ML-amplitudes in patients and controls. Thus, ML-amplitudes declined with age in controls, whereas they increased with age in PD possibly because older patients were more severely affected than younger patients. Thus, the difference between young-onset and late-onset PD seems to be related to the opposite effects of increasing age and disease severity in patients and controls. ML-amplitudes did not differ between patients with MPTP-induced Parkinsonism, patients with young-onset PD and controls, suggesting that supraspinal dopaminergic systems are not critically involved in control of ML responses. This result also indicates that the severity effect in PD may be related to disruption of non-dopaminergic pathways which occurs in late-onset, but not young-onset patients.(ABSTRACT TRUNCATED AT 250 WORDS)
M. T. Herrero - One of the best experts on this subject based on the ideXlab platform.
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Evidence of oligodendrogliosis in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism.
Neuropathology and applied neurobiology, 2013Co-Authors: Valentina Annese, Carlos Barcia, Francisco Ros-bernal, A. Gómez, Carmen María Brugarolas Ros, V. De Pablos, Emiliano Fernández-villalba, M. E. De Stefano, M. T. HerreroAbstract:V. Annese, C. Barcia, F. Ros-Bernal, A. Gomez, C. M. Ros, V. De Pablos, E. Fernandez-Villalba, M.-E. De Stefano and M. T. Herrero (2013) Neuropathology and Applied Neurobiology39, 132–143 Evidence of oligodendrogliosis in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism Aims: Mice and nonhuman primates administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) represent elective experimental models of Parkinsonism, in which degeneration of the nigrostriatal dopaminergic pathway is associated with prominent neuroinflammation, characterized by activated microglia and astrocytes in both substantia nigra (SN) and striatum. To date, it is unknown whether oligodendrocytes play a role in these events. Methods: We performed a detailed qualitative and quantitative analysis of oligodendrocyte-associated changes induced by acute and chronic MPTP treatment, in the SN and striatum of mice and macaques respectively. Oligodendrocytes were immunolabelled by cell-specific markers and analysed by confocal microscopy. Results: In both experimental models, MPTP treatment induces an increase in oligodendrocyte cell number and average size, as well as in the total area occupied by this cell type per tissue section, accompanied by evident morphological changes. This multifaceted array of changes, herein referred to as oligodendrogliosis, significantly correlates with the reduction in the level of dopaminergic innervation to the striatum. Conclusions: This event, associated with early damage of the dopaminergic neurone axons and of the complex striatal circuits of which they are part, may result in an important, although neglected, aspect in the onset and progression of Parkinsonism.
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Evidence of oligodendrogliosis in MPTP-induced Parkinsonism.
Neuropathology and Applied Neurobiology, 2012Co-Authors: Valentina Annese, Carlos Barcia, Francisco Ros-bernal, A. Gómez, Carmen María Brugarolas Ros, V. De Pablos, Emiliano Fernández-villalba, M. E. De Stefano, M. T. HerreroAbstract:Aims: Mice and non-human primates administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) represent elective experimental models of Parkinsonism, in which degeneration of the nigro-striatal dopaminergic pathway is associated with prominent neuroinflammation, characterized by activated microglia and astrocytes in both substantia nigra (SN) and striatum. To date, it is unknown whether oligodendrocytes play a role in these events. Methods: We performed a detailed qualitative and quantitative analysis of oligodendrocyte-associated changes induced by acute and chronic MPTP treatment, in the SN and striatum of mice and macaques, respectively. Oligodendrocytes were immunolabeled by cell-specific markers and analyzed by confocal microscopy. Results: In both experimental models, MPTP treatment induces an increase in oligodendrocyte cell number and average size, as well as in the total area occupied by this cell type per tissue section, accompanied by evident morphological changes. This multifaceted array of changes, herein referred to as oligodendrogliosis, significantly correlate with the reduction in the level of dopaminergic innervation to the striatum. Conclusions: This event, associated with early damage of the dopaminergic neuron axons and of the complex striatal circuits of which they are part, may result in an important, although neglected, aspect in the onset and progression of Parkinsonism. © 2012 The Authors. Neuropathology and Applied Neurobiology © 2012 British Neuropathological Society.
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Subthalamotomy improves MPTP-induced Parkinsonism in monkeys.
Stereotactic and functional neurosurgery, 1994Co-Authors: Jorge Guridi, M. T. Herrero, R. Luquin, J. Guillen, J.a. ObesoAbstract:Hyperactivity of the subthalamic nucleus (STN) is major characteristic of Parkinsonism secondary to substantia nigra lesions. Interruption of the STN-internal pallidum (GPi) pathway is a new stereotac