Electrical stimulation promotes functional recovery after spinal cord injury by activating endogenous spinal cord-derived neural stem/progenitor cell: an in vitro and in vivo study

Woo-Seok Bang; Inbo Han; Seul-Ah Mun; Jong-Moon Hwang; Sung Hyun Noh; Wonsoo Son; Dae-Chul Cho; Byoung-Joon Kim; Chi Heon Kim; Hyuk Choi; Kyoung-Tae Kim

doi:10.1016/j.spinee.2023.10.004

Electrical stimulation promotes functional recovery after spinal cord injury by activating endogenous spinal cord-derived neural stem/progenitor cell: an in vitro and in vivo study

Spine J. 2024 Mar;24(3):534-553. doi: 10.1016/j.spinee.2023.10.004. Epub 2023 Oct 21.

Authors

Woo-Seok Bang¹, Inbo Han², Seul-Ah Mun³, Jong-Moon Hwang⁴, Sung Hyun Noh⁵, Wonsoo Son⁶, Dae-Chul Cho⁷, Byoung-Joon Kim⁸, Chi Heon Kim⁹, Hyuk Choi¹⁰, Kyoung-Tae Kim¹¹

Affiliations

¹ Department of Neurosurgery, Topspine Hospital, Daegu, Republic of Korea. Electronic address: woosugi14@naver.com.
² Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea. Electronic address: hanib@cha.ac.kr.
³ Department. of Neurosurgery, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea. Electronic address: dp3942@naver.com.
⁴ Department of Rehabilitation Medicine, Daegu Fatima Hospital, Daegu, Republic of Korea. Electronic address: hti82@hanmail.net.
⁵ Department of Neurosurgery, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address: juwuman12@gmail.com.
⁶ Department. of Neurosurgery, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea. Electronic address: wsson22@hanmail.net.
⁷ Department. of Neurosurgery, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea. Electronic address: dccho@knu.ac.kr.
⁸ Department. of Neurosurgery, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea. Electronic address: bjkimknuh@gmail.com.
⁹ Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: chiheon1@snu.ac.kr.
¹⁰ Department of Medical Sciences, Graduate School of Medicine, Korea University, Seoul, Republic of Korea. Electronic address: hyuk76@korea.ac.kr.
¹¹ Department. of Neurosurgery, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea. Electronic address: nskimkt7@gmail.com.

PMID: 37871660
DOI: 10.1016/j.spinee.2023.10.004

Abstract

Background context: Electrical stimulation is a noninvasive treatment method that has gained popularity in the treatment of spinal cord injury (SCI). Activation of spinal cord-derived neural stem/progenitor cell (SC-NSPC) proliferation and differentiation in the injured spinal cord may elicit considerable neural regenerative effects.

Purpose: This study aimed to explore the effect of electrical stimulation on the neurogenesis of SC-NSPCs.

Study design: This study analyzed the effects of electrical stimulation on neurogenesis in rodent SC-NSPCs in vitro and in vivo and evaluated functional recovery and neural circuitry improvements with electrical stimulation using a rodent SCI model.

Methods: Rats (20 rats/group) were assigned to sham (Group 1), SCI only (Group 2), SCI + electrode implant without stimulation (Group 3), and SCI + electrode with stimulation (Group 4) groups to count total SC-NSPCs and differentiated neurons and to evaluate morphological changes in differentiated neurons. Furthermore, the Basso, Beattie, and Bresnahan scores were analyzed, and the motor- and somatosensory-evoked potentials in all rats were monitored.

Results: Biphasic electrical currents enhanced SC-NSPC proliferation differentiation and caused qualitative morphological changes in differentiated neurons in vitro. Electrical stimulation promoted SC-NSPC proliferation and neuronal differentiation and improved functional outcomes and neural circuitry in SCI models. Increased Wnt3, Wnt7, and β-catenin protein levels were also observed after electrical stimulation.

Conclusions: Our study proved the beneficial effects of electrical stimulation on SCI. The Wnt/β-catenin pathway activation may be associated with this relationship between electrical stimulation and neuronal regeneration after SCI.

Clinical significance: The study confirmed the benefits of electrical stimulation on SCI based on cellular, functional, electrophysiological, and histological evidence. Based on these findings, we expect electrical stimulation to make a positive and significant difference in SCI treatment strategies.

Keywords: Biphasic electrical current; Neural stem/progenitor cells; Spinal cord injury; Wnt signaling.

MeSH terms

Animals
Cell Differentiation
Neural Stem Cells* / metabolism
Neural Stem Cells* / transplantation
Rats
Recovery of Function
Spinal Cord / metabolism
Spinal Cord Injuries* / pathology
Wnt Signaling Pathway