TY - JOUR
T1 - Treadmill Training for Common Marmoset to Strengthen Corticospinal Connections After Thoracic Contusion Spinal Cord Injury
AU - Kondo, Takahiro
AU - Saito, Risa
AU - Sato, Yuta
AU - Sato, Kenta
AU - Uchida, Akito
AU - Yoshino-Saito, Kimika
AU - Shinozaki, Munehisa
AU - Tashiro, Syoichi
AU - Nagoshi, Narihito
AU - Nakamura, Masaya
AU - Ushiba, Junichi
AU - Okano, Hideyuki
N1 - Funding Information:
This research was supported by General Insurance Association of Japan Medical Research Grants 2021 and by AMED under grant nos. JP21bm0204001h, JSPS KAKENHI, JP19H03983, and JP20H05480.
Funding Information:
JU is the founder and Representative Director of the University Startup Company, Connect, Inc., for the research, development, and sale of rehabilitation devices, including the brain–computer interface. He received a salary from Connect, Inc., and held shares in Connect, Inc. This company has no relationship with the present study. HO is a compensated scientific consultant of San Bio Co., Ltd., and K Pharma, Inc., and has received research funding from Dainippon Sumitomo Pharmaceutical Co., Ltd. MN is a compensated scientific consultant at K Pharma, Inc. YS and TK are founders of ALAN, Inc., and hold shares in ALAN, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher Copyright:
Copyright © 2022 Kondo, Saito, Sato, Sato, Uchida, Yoshino-Saito, Shinozaki, Tashiro, Nagoshi, Nakamura, Ushiba and Okano.
PY - 2022/4/22
Y1 - 2022/4/22
N2 - Spinal cord injury (SCI) leads to locomotor dysfunction. Locomotor rehabilitation promotes the recovery of stepping ability in lower mammals, but it has limited efficacy in humans with a severe SCI. To explain this discrepancy between different species, a nonhuman primate rehabilitation model with a severe SCI would be useful. In this study, we developed a rehabilitation model of paraplegia caused by a severe traumatic SCI in a nonhuman primate, common marmoset (Callithrix jacchus). The locomotor rating scale for marmosets was developed to accurately assess the recovery of locomotor functions in marmosets. All animals showed flaccid paralysis of the hindlimb after a thoracic contusive SCI, but the trained group showed significant locomotor recovery. Kinematic analysis revealed significantly improved hindlimb stepping patterns in trained marmosets. Furthermore, intracortical microstimulation (ICMS) of the motor cortex evoked the hindlimb muscles in the trained group, suggesting the reconnection between supraspinal input and the lumbosacral network. Because rehabilitation may be combined with regenerative interventions such as medicine or cell therapy, this primate model can be used as a preclinical test of therapies that can be used in human clinical trials.
AB - Spinal cord injury (SCI) leads to locomotor dysfunction. Locomotor rehabilitation promotes the recovery of stepping ability in lower mammals, but it has limited efficacy in humans with a severe SCI. To explain this discrepancy between different species, a nonhuman primate rehabilitation model with a severe SCI would be useful. In this study, we developed a rehabilitation model of paraplegia caused by a severe traumatic SCI in a nonhuman primate, common marmoset (Callithrix jacchus). The locomotor rating scale for marmosets was developed to accurately assess the recovery of locomotor functions in marmosets. All animals showed flaccid paralysis of the hindlimb after a thoracic contusive SCI, but the trained group showed significant locomotor recovery. Kinematic analysis revealed significantly improved hindlimb stepping patterns in trained marmosets. Furthermore, intracortical microstimulation (ICMS) of the motor cortex evoked the hindlimb muscles in the trained group, suggesting the reconnection between supraspinal input and the lumbosacral network. Because rehabilitation may be combined with regenerative interventions such as medicine or cell therapy, this primate model can be used as a preclinical test of therapies that can be used in human clinical trials.
KW - kinematics
KW - locomotion
KW - marmoset
KW - rehabilitation
KW - spinal cord injury
KW - treadmill training
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U2 - 10.3389/fncel.2022.858562
DO - 10.3389/fncel.2022.858562
M3 - Article
AN - SCOPUS:85129747810
SN - 1662-5102
VL - 16
JO - Frontiers in Cellular Neuroscience
JF - Frontiers in Cellular Neuroscience
M1 - 858562
ER -