Cargando…

Deep brain stimulation of midbrain locomotor circuits in the freely moving pig

BACKGROUND: Deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR) has been studied as a therapeutic target in rodent models of stroke, parkinsonism, and spinal cord injury. Clinical DBS trials have targeted the closely related pedunculopontine nucleus in patients with Parkinson’s...

Descripción completa

Detalles Bibliográficos
Autores principales: Chang, Stephano J., Santamaria, Andrea J., Sanchez, Francisco J., Villamil, Luz M., Pinheiro Saraiva, Pedro, Benavides, Francisco, Nunez-Gomez, Yohjans, Solano, Juan P., Opris, Ioan, Guest, James D., Noga, Brian R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097921/
https://www.ncbi.nlm.nih.gov/pubmed/33652130
http://dx.doi.org/10.1016/j.brs.2021.02.017
_version_ 1784706269709336576
author Chang, Stephano J.
Santamaria, Andrea J.
Sanchez, Francisco J.
Villamil, Luz M.
Pinheiro Saraiva, Pedro
Benavides, Francisco
Nunez-Gomez, Yohjans
Solano, Juan P.
Opris, Ioan
Guest, James D.
Noga, Brian R.
author_facet Chang, Stephano J.
Santamaria, Andrea J.
Sanchez, Francisco J.
Villamil, Luz M.
Pinheiro Saraiva, Pedro
Benavides, Francisco
Nunez-Gomez, Yohjans
Solano, Juan P.
Opris, Ioan
Guest, James D.
Noga, Brian R.
author_sort Chang, Stephano J.
collection PubMed
description BACKGROUND: Deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR) has been studied as a therapeutic target in rodent models of stroke, parkinsonism, and spinal cord injury. Clinical DBS trials have targeted the closely related pedunculopontine nucleus in patients with Parkinson’s disease as a therapy for gait dysfunction, with mixed reported outcomes. Recent studies suggest that optimizing the MLR target could improve its effectiveness. OBJECTIVE: We sought to determine if stereotaxic targeting and DBS in the midbrain of the pig, in a region anatomically similar to that previously identified as the MLR in other species, could initiate and modulate ongoing locomotion, as a step towards generating a large animal neuromodulation model of gait. METHODS: We implanted Medtronic 3389 electrodes into putative MLR structures in Yucatan micropigs to characterize the locomotor effects of acute DBS in this region, using EMG recordings, joint kinematics, and speed measurements on a manual treadmill. RESULTS: MLR DBS initiated and augmented locomotion in freely moving micropigs. Effective locomotor sites centered around the cuneiform nucleus and stimulation frequency controlled locomotor speed and stepping frequency. Off-target stimulation evoked defensive and aversive behaviors that precluded locomotion in the animals. CONCLUSION: Pigs appear to have an MLR and can be used to model neuromodulation of this gait-promoting center. These results indicate that the pig is a useful model to guide future clinical studies for optimizing MLR DBS in cases of gait deficiencies associated with such conditions as Parkinson’s disease, spinal cord injury, or stroke.
format Online
Article
Text
id pubmed-9097921
institution National Center for Biotechnology Information
language English
publishDate 2021
record_format MEDLINE/PubMed
spelling pubmed-90979212022-05-12 Deep brain stimulation of midbrain locomotor circuits in the freely moving pig Chang, Stephano J. Santamaria, Andrea J. Sanchez, Francisco J. Villamil, Luz M. Pinheiro Saraiva, Pedro Benavides, Francisco Nunez-Gomez, Yohjans Solano, Juan P. Opris, Ioan Guest, James D. Noga, Brian R. Brain Stimul Article BACKGROUND: Deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR) has been studied as a therapeutic target in rodent models of stroke, parkinsonism, and spinal cord injury. Clinical DBS trials have targeted the closely related pedunculopontine nucleus in patients with Parkinson’s disease as a therapy for gait dysfunction, with mixed reported outcomes. Recent studies suggest that optimizing the MLR target could improve its effectiveness. OBJECTIVE: We sought to determine if stereotaxic targeting and DBS in the midbrain of the pig, in a region anatomically similar to that previously identified as the MLR in other species, could initiate and modulate ongoing locomotion, as a step towards generating a large animal neuromodulation model of gait. METHODS: We implanted Medtronic 3389 electrodes into putative MLR structures in Yucatan micropigs to characterize the locomotor effects of acute DBS in this region, using EMG recordings, joint kinematics, and speed measurements on a manual treadmill. RESULTS: MLR DBS initiated and augmented locomotion in freely moving micropigs. Effective locomotor sites centered around the cuneiform nucleus and stimulation frequency controlled locomotor speed and stepping frequency. Off-target stimulation evoked defensive and aversive behaviors that precluded locomotion in the animals. CONCLUSION: Pigs appear to have an MLR and can be used to model neuromodulation of this gait-promoting center. These results indicate that the pig is a useful model to guide future clinical studies for optimizing MLR DBS in cases of gait deficiencies associated with such conditions as Parkinson’s disease, spinal cord injury, or stroke. 2021 2021-02-27 /pmc/articles/PMC9097921/ /pubmed/33652130 http://dx.doi.org/10.1016/j.brs.2021.02.017 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Chang, Stephano J.
Santamaria, Andrea J.
Sanchez, Francisco J.
Villamil, Luz M.
Pinheiro Saraiva, Pedro
Benavides, Francisco
Nunez-Gomez, Yohjans
Solano, Juan P.
Opris, Ioan
Guest, James D.
Noga, Brian R.
Deep brain stimulation of midbrain locomotor circuits in the freely moving pig
title Deep brain stimulation of midbrain locomotor circuits in the freely moving pig
title_full Deep brain stimulation of midbrain locomotor circuits in the freely moving pig
title_fullStr Deep brain stimulation of midbrain locomotor circuits in the freely moving pig
title_full_unstemmed Deep brain stimulation of midbrain locomotor circuits in the freely moving pig
title_short Deep brain stimulation of midbrain locomotor circuits in the freely moving pig
title_sort deep brain stimulation of midbrain locomotor circuits in the freely moving pig
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097921/
https://www.ncbi.nlm.nih.gov/pubmed/33652130
http://dx.doi.org/10.1016/j.brs.2021.02.017
work_keys_str_mv AT changstephanoj deepbrainstimulationofmidbrainlocomotorcircuitsinthefreelymovingpig
AT santamariaandreaj deepbrainstimulationofmidbrainlocomotorcircuitsinthefreelymovingpig
AT sanchezfranciscoj deepbrainstimulationofmidbrainlocomotorcircuitsinthefreelymovingpig
AT villamilluzm deepbrainstimulationofmidbrainlocomotorcircuitsinthefreelymovingpig
AT pinheirosaraivapedro deepbrainstimulationofmidbrainlocomotorcircuitsinthefreelymovingpig
AT benavidesfrancisco deepbrainstimulationofmidbrainlocomotorcircuitsinthefreelymovingpig
AT nunezgomezyohjans deepbrainstimulationofmidbrainlocomotorcircuitsinthefreelymovingpig
AT solanojuanp deepbrainstimulationofmidbrainlocomotorcircuitsinthefreelymovingpig
AT oprisioan deepbrainstimulationofmidbrainlocomotorcircuitsinthefreelymovingpig
AT guestjamesd deepbrainstimulationofmidbrainlocomotorcircuitsinthefreelymovingpig
AT nogabrianr deepbrainstimulationofmidbrainlocomotorcircuitsinthefreelymovingpig