Stimulation of the cuneiform nucleus enables training and boosts recovery after spinal cord injury.


Journal

Brain : a journal of neurology
ISSN: 1460-2156
Titre abrégé: Brain
Pays: England
ID NLM: 0372537

Informations de publication

Date de publication:
21 10 2022
Historique:
received: 01 01 2022
revised: 07 04 2022
accepted: 04 05 2022
pubmed: 19 5 2022
medline: 26 10 2022
entrez: 18 5 2022
Statut: ppublish

Résumé

Severe spinal cord injuries result in permanent paraparesis in spite of the frequent sparing of small portions of white matter. Spared fibre tracts are often incapable of maintaining and modulating the activity of lower spinal motor centres. Effects of rehabilitative training thus remain limited. Here, we activated spared descending brainstem fibres by electrical deep brain stimulation of the cuneiform nucleus of the mesencephalic locomotor region, the main control centre for locomotion in the brainstem, in adult female Lewis rats. We show that deep brain stimulation of the cuneiform nucleus enhances the weak remaining motor drive in highly paraparetic rats with severe, incomplete spinal cord injuries and enables high-intensity locomotor training. Stimulation of the cuneiform nucleus during rehabilitative aquatraining after subchronic (n = 8 stimulated versus n = 7 unstimulated versus n = 7 untrained rats) and chronic (n = 14 stimulated versus n = 9 unstimulated versus n = 9 untrained rats) spinal cord injury re-established substantial locomotion and improved long-term recovery of motor function. We additionally identified a safety window of stimulation parameters ensuring context-specific locomotor control in intact rats (n = 18) and illustrate the importance of timing of treatment initiation after spinal cord injury (n = 14). This study highlights stimulation of the cuneiform nucleus as a highly promising therapeutic strategy to enhance motor recovery after subchronic and chronic incomplete spinal cord injury with direct clinical applicability.

Identifiants

pubmed: 35583160
pii: 6587425
doi: 10.1093/brain/awac184
pmc: PMC9586551
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3681-3697

Informations de copyright

© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.

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Auteurs

Anna-Sophie Hofer (AS)

Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
Institute for Regenerative Medicine, University of Zurich, 8952 Schlieren, Switzerland.
Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland.

Myriam I Scheuber (MI)

Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
Institute for Regenerative Medicine, University of Zurich, 8952 Schlieren, Switzerland.
Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland.

Andrea M Sartori (AM)

Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
Institute for Regenerative Medicine, University of Zurich, 8952 Schlieren, Switzerland.
Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland.

Nicolas Good (N)

Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
Institute for Regenerative Medicine, University of Zurich, 8952 Schlieren, Switzerland.
Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland.

Stephanie A Stalder (SA)

Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland.

Nicole Hammer (N)

Institute for Regenerative Medicine, University of Zurich, 8952 Schlieren, Switzerland.
Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland.

Kai Fricke (K)

Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland.

Sina M Schalbetter (SM)

Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
Institute for Regenerative Medicine, University of Zurich, 8952 Schlieren, Switzerland.
Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland.

Anne K Engmann (AK)

Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland.

Rebecca Z Weber (RZ)

Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
Institute for Regenerative Medicine, University of Zurich, 8952 Schlieren, Switzerland.
Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland.

Ruslan Rust (R)

Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
Institute for Regenerative Medicine, University of Zurich, 8952 Schlieren, Switzerland.
Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland.

Marc P Schneider (MP)

Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland.

Natalie Russi (N)

Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland.

Giacomin Favre (G)

Department of Economics, University of Zurich, 8032 Zurich, Switzerland.

Martin E Schwab (ME)

Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
Institute for Regenerative Medicine, University of Zurich, 8952 Schlieren, Switzerland.
Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland.

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