Stimulation of the rat subthalamic nucleus is neuroprotective following significant nigral dopamine neuron loss

A. L. Spieles-Engemann; M. M. Behbehani; T. J. Collier; S. L. Wohlgenant; K. Steece-Collier; K. Paumier; B. F. Daley; S. Gombash; L. Madhavan; G. T. Mandybur; J. W. Lipton; B. T. Terpstra; C. E. Sortwell

doi:10.1016/j.nbd.2010.03.009

Stimulation of the rat subthalamic nucleus is neuroprotective following significant nigral dopamine neuron loss

A. L. Spieles-Engemann, M. M. Behbehani, T. J. Collier, S. L. Wohlgenant, K. Steece-Collier, K. Paumier, B. F. Daley, S. Gombash, L. Madhavan, G. T. Mandybur, J. W. Lipton, B. T. Terpstra, C. E. Sortwell

Research output: Contribution to journal › Article › peer-review

116 Scopus citations

Abstract

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is efficacious in treating the motor symptoms of Parkinson's disease (PD). However, the impact of STN-DBS on the progression of PD is unknown. Previous preclinical studies have demonstrated that STN-DBS can attenuate the degeneration of a relatively intact nigrostriatal system from dopamine (DA)-depleting neurotoxins. The present study examined whether STN-DBS can provide neuroprotection in the face of prior significant nigral DA neuron loss similar to PD patients at the time of diagnosis. STN-DBS between 2 and 4. weeks after intrastriatal 6-hydroxydopamine (6-OHDA) provided significant sparing of DA neurons in the SN of rats. This effect was not due to inadvertent lesioning of the STN and was dependent upon proper electrode placement. Since STN-DBS appears to have significant neuroprotective properties, initiation of STN-DBS earlier in the course of PD may provide added neuroprotective benefits in addition to its ability to provide symptomatic relief.

Original language	English (US)
Pages (from-to)	105-115
Number of pages	11
Journal	Neurobiology of Disease
Volume	39
Issue number	1
DOIs	https://doi.org/10.1016/j.nbd.2010.03.009
State	Published - Jul 2010
Externally published	Yes

Keywords

6-hydroxydopamine
Deep brain stimulation
Neuroprotection
Parkinson's disease
Stereology
Subthalamic nucleus

ASJC Scopus subject areas

Neurology

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Spieles-Engemann, A. L., Behbehani, M. M., Collier, T. J., Wohlgenant, S. L., Steece-Collier, K., Paumier, K., Daley, B. F., Gombash, S., Madhavan, L., Mandybur, G. T., Lipton, J. W., Terpstra, B. T., & Sortwell, C. E. (2010). Stimulation of the rat subthalamic nucleus is neuroprotective following significant nigral dopamine neuron loss. Neurobiology of Disease, 39(1), 105-115. https://doi.org/10.1016/j.nbd.2010.03.009

Spieles-Engemann, AL, Behbehani, MM, Collier, TJ, Wohlgenant, SL, Steece-Collier, K, Paumier, K, Daley, BF, Gombash, S, Madhavan, L, Mandybur, GT, Lipton, JW, Terpstra, BT & Sortwell, CE 2010, 'Stimulation of the rat subthalamic nucleus is neuroprotective following significant nigral dopamine neuron loss', Neurobiology of Disease, vol. 39, no. 1, pp. 105-115. https://doi.org/10.1016/j.nbd.2010.03.009

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title = "Stimulation of the rat subthalamic nucleus is neuroprotective following significant nigral dopamine neuron loss",

abstract = "Deep brain stimulation of the subthalamic nucleus (STN-DBS) is efficacious in treating the motor symptoms of Parkinson's disease (PD). However, the impact of STN-DBS on the progression of PD is unknown. Previous preclinical studies have demonstrated that STN-DBS can attenuate the degeneration of a relatively intact nigrostriatal system from dopamine (DA)-depleting neurotoxins. The present study examined whether STN-DBS can provide neuroprotection in the face of prior significant nigral DA neuron loss similar to PD patients at the time of diagnosis. STN-DBS between 2 and 4. weeks after intrastriatal 6-hydroxydopamine (6-OHDA) provided significant sparing of DA neurons in the SN of rats. This effect was not due to inadvertent lesioning of the STN and was dependent upon proper electrode placement. Since STN-DBS appears to have significant neuroprotective properties, initiation of STN-DBS earlier in the course of PD may provide added neuroprotective benefits in addition to its ability to provide symptomatic relief.",

keywords = "6-hydroxydopamine, Deep brain stimulation, Neuroprotection, Parkinson's disease, Stereology, Subthalamic nucleus",

author = "Spieles-Engemann, {A. L.} and Behbehani, {M. M.} and Collier, {T. J.} and Wohlgenant, {S. L.} and K. Steece-Collier and K. Paumier and Daley, {B. F.} and S. Gombash and L. Madhavan and Mandybur, {G. T.} and Lipton, {J. W.} and Terpstra, {B. T.} and Sortwell, {C. E.}",

note = "Funding Information: We are thankful for the excellent technical assistance of Mr. James Lee in the execution of this project. We are also grateful for the input and insight of Dr. P. David Charles and Dr. Helen Bronte-Stewart. This work was supported by the University of Cincinnati , the Davis Phinney Foundation for Parkinson's Research , NS064696 (ASE), and the Udall Parkinson's Disease Research Center of Excellence at the University of Cincinnati NS058830 (TJC).",

year = "2010",

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doi = "10.1016/j.nbd.2010.03.009",

language = "English (US)",

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AU - Behbehani, M. M.

AU - Collier, T. J.

AU - Wohlgenant, S. L.

AU - Steece-Collier, K.

AU - Paumier, K.

AU - Daley, B. F.

AU - Gombash, S.

AU - Madhavan, L.

AU - Mandybur, G. T.

AU - Lipton, J. W.

AU - Terpstra, B. T.

AU - Sortwell, C. E.

N1 - Funding Information: We are thankful for the excellent technical assistance of Mr. James Lee in the execution of this project. We are also grateful for the input and insight of Dr. P. David Charles and Dr. Helen Bronte-Stewart. This work was supported by the University of Cincinnati , the Davis Phinney Foundation for Parkinson's Research , NS064696 (ASE), and the Udall Parkinson's Disease Research Center of Excellence at the University of Cincinnati NS058830 (TJC).

PY - 2010/7

Y1 - 2010/7

N2 - Deep brain stimulation of the subthalamic nucleus (STN-DBS) is efficacious in treating the motor symptoms of Parkinson's disease (PD). However, the impact of STN-DBS on the progression of PD is unknown. Previous preclinical studies have demonstrated that STN-DBS can attenuate the degeneration of a relatively intact nigrostriatal system from dopamine (DA)-depleting neurotoxins. The present study examined whether STN-DBS can provide neuroprotection in the face of prior significant nigral DA neuron loss similar to PD patients at the time of diagnosis. STN-DBS between 2 and 4. weeks after intrastriatal 6-hydroxydopamine (6-OHDA) provided significant sparing of DA neurons in the SN of rats. This effect was not due to inadvertent lesioning of the STN and was dependent upon proper electrode placement. Since STN-DBS appears to have significant neuroprotective properties, initiation of STN-DBS earlier in the course of PD may provide added neuroprotective benefits in addition to its ability to provide symptomatic relief.

AB - Deep brain stimulation of the subthalamic nucleus (STN-DBS) is efficacious in treating the motor symptoms of Parkinson's disease (PD). However, the impact of STN-DBS on the progression of PD is unknown. Previous preclinical studies have demonstrated that STN-DBS can attenuate the degeneration of a relatively intact nigrostriatal system from dopamine (DA)-depleting neurotoxins. The present study examined whether STN-DBS can provide neuroprotection in the face of prior significant nigral DA neuron loss similar to PD patients at the time of diagnosis. STN-DBS between 2 and 4. weeks after intrastriatal 6-hydroxydopamine (6-OHDA) provided significant sparing of DA neurons in the SN of rats. This effect was not due to inadvertent lesioning of the STN and was dependent upon proper electrode placement. Since STN-DBS appears to have significant neuroprotective properties, initiation of STN-DBS earlier in the course of PD may provide added neuroprotective benefits in addition to its ability to provide symptomatic relief.

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Stimulation of the rat subthalamic nucleus is neuroprotective following significant nigral dopamine neuron loss

Abstract

Keywords

ASJC Scopus subject areas

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