Double-target magnetic stimulation attenuates oligodendrocyte apoptosis and oxidative stress impairment after spinal cord injury via GAP43.

Background context: Spinal cord injury (SCI) causes neural circuit interruption and permanent functional damage. Magnetic stimulation in humans with SCI aims to engage residual neural networks to improve neurological functional, but the detailed mechanism remains unknown.

Purpose: This study evaluates functional recovery and neural circuitry improvements in rodent with double-target (brain and spinal cord) magnetic stimulation (DTMS) treatment and explores the effect of DTMS on the modulation of glial cells in vivo and in vitro.

Study design: In vivo animal study.

Methods: SCI model rats at T10 level were induced via a weight-drop method and underwent long-time DTMS treatment. A series of behavioral assessments and tissue staining were used to evaluate neurological function and neural circuitry improvements. More importantly, single-cell RNA sequencing was conducted to identify the most significant glial cells after DTMS treatment. Furthermore, transmission electron microscopy, western blotting, immunofluorescence staining, TUNEL staining, Annexin V-FITC apoptosis kit and Lipid ROS kit were used to explore the mechanism underlying the observed changes. Study funding sources: National Natural Science Foundation of China (Grant number: U22A20297; Dollar amount: 62500); Key Research and Development Program of Guangzhou (Grant number: 202206060003; Dollar amount: 63750). There are no conflicts of interest or disclosures to report.

Results: DTMS promoted the improvements of motor and sensory neural circuitry by modulating remyelination and neuronal survival, while silencing growth-associated protein 43 (GAP43) in oligodendrocytes suppressed these effects of DTMS in vivo. Mechanically, GAP43 played a crucial part to promote the branching and mature of oligodendrocytes and axonal regeneration via anti-apoptotic and anti-oxidative stress effects. Furthermore, oligodendrocytes subjected to magnetic stimulation exerted neuroprotective effects on neurons by secreting exosomes containing GAP43.

Conclusions: Our study revealed the neuroprotection of DTMS on SCI. The GAP43 in oligodendrocytes were associated with this relationship between magnetic stimulation and myelin and neuronal regeneration after SCI.

Clinical significance: The current study demonstrated the beneficial effects of DTMS on SCI based on functional, electrophysiological, cellular and histological evidence. According to these findings, we expect DTMS to make a positive and significant difference for SCI therapeutic screening.