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Int. J. Mol. Sci. 2018, 19(6), 1701; https://doi.org/10.3390/ijms19061701

Activity-Based Physical Rehabilitation with Adjuvant Testosterone to Promote Neuromuscular Recovery after Spinal Cord Injury

1
Brain Rehabilitation Research Center, Malcom Randall Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL 32608, USA
2
Research Service, Malcom Randall Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL 32608, USA
3
Department of Applied Physiology, Kinesiology and University of Florida College of Health and Human Performance, Gainesville, FL 32603, USA
4
Division of Endocrinology, Diabetes and Metabolism, University of Florida College of Medicine, Gainesville, FL 32610, USA
*
Author to whom correspondence should be addressed.
Received: 21 April 2018 / Revised: 31 May 2018 / Accepted: 1 June 2018 / Published: 7 June 2018
(This article belongs to the Special Issue Therapeutic Strategies to Spinal Cord Injury)
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Abstract

Neuromuscular impairment and reduced musculoskeletal integrity are hallmarks of spinal cord injury (SCI) that hinder locomotor recovery. These impairments are precipitated by the neurological insult and resulting disuse, which has stimulated interest in activity-based physical rehabilitation therapies (ABTs) that promote neuromuscular plasticity after SCI. However, ABT efficacy declines as SCI severity increases. Additionally, many men with SCI exhibit low testosterone, which may exacerbate neuromusculoskeletal impairment. Incorporating testosterone adjuvant to ABTs may improve musculoskeletal recovery and neuroplasticity because androgens attenuate muscle loss and the slow-to-fast muscle fiber-type transition after SCI, in a manner independent from mechanical strain, and promote motoneuron survival. These neuromusculoskeletal benefits are promising, although testosterone alone produces only limited functional improvement in rodent SCI models. In this review, we discuss the (1) molecular deficits underlying muscle loss after SCI; (2) independent influences of testosterone and locomotor training on neuromuscular function and musculoskeletal integrity post-SCI; (3) hormonal and molecular mechanisms underlying the therapeutic efficacy of these strategies; and (4) evidence supporting a multimodal strategy involving ABT with adjuvant testosterone, as a potential means to promote more comprehensive neuromusculoskeletal recovery than either strategy alone. View Full-Text
Keywords: neuroplasticity; bodyweight-supported treadmill training; estradiol; estrogen; muscle; PI3K; IGF-1; motor neuron; BDNF; FOXO; PGC-1 alpha; PGC-1 beta neuroplasticity; bodyweight-supported treadmill training; estradiol; estrogen; muscle; PI3K; IGF-1; motor neuron; BDNF; FOXO; PGC-1 alpha; PGC-1 beta
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Otzel, D.M.; Lee, J.; Ye, F.; Borst, S.E.; Yarrow, J.F. Activity-Based Physical Rehabilitation with Adjuvant Testosterone to Promote Neuromuscular Recovery after Spinal Cord Injury. Int. J. Mol. Sci. 2018, 19, 1701.

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