Dual motor cortex and spinal cord neuromodulation improves rehabilitation efficacy and restores skilled locomotor function in a rat cervical contusion injury model.
Animals
Cervical Cord
/ injuries
Contusions
/ physiopathology
Electrodes, Implanted
Female
Locomotion
/ physiology
Motor Cortex
/ physiology
Neurological Rehabilitation
/ methods
Neuronal Plasticity
/ physiology
Rats
Rats, Sprague-Dawley
Recovery of Function
/ physiology
Spinal Cord
/ physiology
Spinal Cord Injuries
/ physiopathology
Spinal Cord Stimulation
/ methods
Transcranial Direct Current Stimulation
/ methods
Treatment Outcome
Axon sprouting
Corticospinal tract
Electrical stimulation
Motor cortex stimulation
Proprioceptive afferents
Trans-spinal direct current stimulation
Journal
Experimental neurology
ISSN: 1090-2430
Titre abrégé: Exp Neurol
Pays: United States
ID NLM: 0370712
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
27
11
2020
revised:
14
03
2021
accepted:
31
03
2021
pubmed:
6
4
2021
medline:
5
10
2021
entrez:
5
4
2021
Statut:
ppublish
Résumé
Motor recovery after spinal cord injury is limited due to sparse descending pathway axons caudal to the injury. Rehabilitation is the primary treatment for paralysis in humans with SCI, but only produces modest functional recovery. Here, we determined if dual epidural motor cortex (M1) intermittent theta burst stimulation (iTBS) and cathodal transcutaneous spinal direct stimulation (tsDCS) enhances the efficacy of rehabilitation in improving motor function after cervical SCI. iTBS produces CST axon sprouting and tsDCS enhances M1-evoked spinal activity and muscle contractions after SCI. Rats were trained to perform the horizontal ladder task. Animals received a moderate midline C4 contusion, producing bilateral forelimb impairments. After 2 weeks, animals either received 10 days of iTBS+tsDCS or no stimulation; subsequently, all animals received 6 weeks of daily rehabilitation on the horizontal ladder task. Lesion size was not different in the two animal groups. Rehabilitation alone improved performance by a 22% reduction in skilled locomotion error rate, whereas stimulation+rehabilitation was markedly more effective (52%), and restored error rate to pre-injury levels. Stimulation+rehabilitation significantly increased CST axon length caudal to the injury and the amount of ventral horn label was positively correlated with functional improvement. The stimulation+rehabilitation group had significantly less proprioceptive afferent terminal labelling in the intermediate zone and fewer synapses on motoneurons . Afferent fiber terminal labeling was negatively correlated with motor recovery. Thus, the dual neuromodulation protocol promotes adaptive plasticity in corticospinal and proprioceptive afferents networks after contusion SCI, leading to enhanced rehabilitation efficacy and recovery of skilled locomotion.
Identifiants
pubmed: 33819448
pii: S0014-4886(21)00121-7
doi: 10.1016/j.expneurol.2021.113715
pmc: PMC10150584
mid: NIHMS1694699
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
113715Subventions
Organisme : NINDS NIH HHS
ID : R01 NS064004
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Références
Nat Neurosci. 2018 Apr;21(4):457-458
pubmed: 29556026
Restor Neurol Neurosci. 2011;29(2):91-103
pubmed: 21701061
Cell Rep. 2019 Apr 2;27(1):71-85.e3
pubmed: 30943416
J Neurosci Methods. 2002 Apr 15;115(2):169-79
pubmed: 11992668
J Neurosci. 2012 Sep 12;32(37):12896-908
pubmed: 22973013
J Neurosci. 2004 Jan 21;24(3):605-14
pubmed: 14736845
Neurosurg Clin N Am. 2017 Jan;28(1):63-71
pubmed: 27886883
Exp Neurol. 2016 Mar;277:46-57
pubmed: 26708732
J Neurocytol. 2000 Jul;29(7):499-507
pubmed: 11279365
Spinal Cord. 2012 Mar;50(3):220-6
pubmed: 21912402
Front Integr Neurosci. 2014 Jun 18;8:51
pubmed: 24994971
J Neurotrauma. 2004 Oct;21(10):1371-83
pubmed: 15672628
Elife. 2016 Oct 19;5:
pubmed: 27759565
J Neurosci. 2011 Jun 22;31(25):9332-44
pubmed: 21697383
Neurosci Biobehav Rev. 2007;31(8):1125-35
pubmed: 17599407
Brain. 2018 Jul 1;141(7):1946-1962
pubmed: 29860396
J Neurosci. 2004 May 26;24(21):4952-61
pubmed: 15163687
PLoS One. 2015 Jul 24;10(7):e0133998
pubmed: 26207623
J Neurophysiol. 2015 Apr 1;113(7):2801-11
pubmed: 25673738
Front Integr Neurosci. 2014 May 12;8:36
pubmed: 24860447
J Neurosci. 2008 Jul 16;28(29):7426-34
pubmed: 18632946
Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2448-53
pubmed: 17287343
NeuroRehabilitation. 2016 Jul 15;39(3):401-11
pubmed: 27589510
J Neurophysiol. 1998 Jul;80(1):83-91
pubmed: 9658030
Lancet. 2011 Jun 4;377(9781):1938-47
pubmed: 21601270
Front Syst Neurosci. 2020 Jun 30;14:35
pubmed: 32714156
J Neurosci. 2017 Nov 8;37(45):10983-10997
pubmed: 29025926
J Neurophysiol. 2005 May;93(5):2822-31
pubmed: 15574795
J Neurotrauma. 2017 May 1;34(9):1787-1802
pubmed: 27566051
J Neurosci. 2018 Sep 26;38(39):8329-8344
pubmed: 30049887
Exp Brain Res. 2004 Aug;157(3):377-82
pubmed: 15221178
J Neurosci. 2007 Dec 12;27(50):13793-801
pubmed: 18077691
J Neurosci. 2016 Apr 06;36(14):4080-92
pubmed: 27053214
Behav Brain Res. 2010 Dec 25;214(2):323-31
pubmed: 20573587
Exp Neurol. 2011 May;229(1):120-31
pubmed: 20633558
Exp Neurol. 2013 Sep;247:605-14
pubmed: 23470552
Exp Neurol. 2020 Feb;324:113136
pubmed: 31786212
J Neurosci. 2007 Oct 10;27(41):11083-90
pubmed: 17928450
J Neurophysiol. 2005 Jul;94(1):255-64
pubmed: 15985696
J Comp Neurol. 2004 May 3;472(3):257-80
pubmed: 15065123
Neuron. 2005 Jan 20;45(2):201-6
pubmed: 15664172
Brain. 2007 Nov;130(Pt 11):2993-3003
pubmed: 17928316
Exp Neurol. 2019 Nov;321:113015
pubmed: 31326353
J Neurosci. 2014 Jan 8;34(2):462-6
pubmed: 24403146
Spinal Cord. 2020 Jun;58(6):635-646
pubmed: 32066873
PLoS One. 2013 Sep 18;8(9):e74454
pubmed: 24058570
Exp Neurol. 2018 Sep;307:133-144
pubmed: 29729248
J Neurosci. 2016 Jan 06;36(1):193-203
pubmed: 26740661
Exp Neurol. 2017 Jun;292:135-144
pubmed: 28341461
Neuroscientist. 2005 Apr;11(2):161-73
pubmed: 15746384
Exp Neurol. 2009 Nov;220(1):9-22
pubmed: 19559699
Cell Rep. 2018 May 1;23(5):1286-1300.e7
pubmed: 29719245
J Neurosci. 2010 Aug 11;30(32):10918-26
pubmed: 20702720
Exp Neurol. 2019 Oct;320:112962
pubmed: 31125548
J Neurotrauma. 2000 Jan;17(1):1-17
pubmed: 10674754
Annu Rev Neurosci. 2008;31:195-218
pubmed: 18558853
Spinal Cord. 2009 Mar;47(3):184-95
pubmed: 18725889
Exp Neurol. 2021 May;339:113543
pubmed: 33290776
N Engl J Med. 2018 Sep 27;379(13):1244-1250
pubmed: 30247091
Exerc Sport Sci Rev. 2015 Apr;43(2):100-6
pubmed: 25607282
Exp Neurol. 2014 Feb;252:47-56
pubmed: 24291254
Nat Neurosci. 2018 Dec;21(12):1728-1741
pubmed: 30382196
Neuron. 2012 Jun 7;74(5):777-91
pubmed: 22681683
J Neurosci. 2004 Mar 3;24(9):2122-32
pubmed: 14999063
Ann Phys Rehabil Med. 2020 May;63(3):230-240
pubmed: 31233828
Neuron. 2009 Dec 10;64(5):645-62
pubmed: 20005822
Science. 2014 Jun 13;344(6189):1250-5
pubmed: 24926013
Sci Rep. 2017 Oct 26;7(1):13476
pubmed: 29074997
J Neuroeng Rehabil. 2017 Mar 21;14(1):22
pubmed: 28327161
Exp Neurol. 2017 Nov;297:179-189
pubmed: 28803750