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

Autor: Chang SJ; Neuroscience Graduate Program, University of Miami Miller School of Medicine, Miami, FL, USA; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA; Division of Neurosurgery, Department of Surgery, University of British Columbia, Vancouver, BC, Canada., Santamaria AJ; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA., Sanchez FJ; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA., Villamil LM; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA., Saraiva PP; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA., Benavides F; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA., Nunez-Gomez Y; Department of Pediatric Critical Care, University of Miami Miller School of Medicine, Miami, FL, USA., Solano JP; Department of Pediatric Critical Care, University of Miami Miller School of Medicine, Miami, FL, USA., Opris I; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA., Guest JD; Neuroscience Graduate Program, University of Miami Miller School of Medicine, Miami, FL, USA; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA., Noga BR; Neuroscience Graduate Program, University of Miami Miller School of Medicine, Miami, FL, USA; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: bnoga@miami.edu.
Jazyk: angličtina
Zdroj: Brain stimulation [Brain Stimul] 2021 May-Jun; Vol. 14 (3), pp. 467-476. Date of Electronic Publication: 2021 Feb 27.
DOI: 10.1016/j.brs.2021.02.017
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare no conflicts of interest.
(Copyright © 2021. Published by Elsevier Inc.)
Databáze: MEDLINE
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