REPETITIVE TRANS-SPINAL MAGNETIC STIMULATION PROMOTES REPAIR IN INFLAMMATORY SPINAL CORD INJURY THROUGH SEX-DEPENDENT IMMUNE MODULATION

Spinal cord injuries (SCI), whether traumatic or inflammatory in origin, are characterized by neuroinflammation, demyelination, and functional disabilities. Current therapeutic options remain limited, underscoring the urgent need for novel, non-invasive treatment strategies. Repetitive magnetic stimulation (RMS) has recently emerged as a promising neuromodulatory approach; however, its mechanisms of action and therapeutic efficacy in inflammatory contexts remain poorly understood.
In this study, we investigated the effects of RMS applied as repetitive trans-spinal magnetic stimulation (rTSMS) in a mouse model of focal spinal cord demyelination induced by lysophosphatidylcholine (LPC). Our results demonstrate that when rTSMS is initiated one day after LPC injection, it significantly attenuates neuroinflammation, reduces demyelination, and limits fibroglial scar formation. These effects are associated with recovery of locomotor function in both sexes. In contrast, when rTSMS treatment is initiated three days after LPC injection—corresponding to the peak of motor deficits—the therapy confers significant tissue protection and functional improvement exclusively in female mice. To further elucidate the biological mechanisms underlying these sex-dependent effects, we performed RNA sequencing analyses. These analyses revealed distinct patterns of immune modulation: in female mice, rTSMS predominantly regulated adaptive immune pathways, whereas in male mice, it primarily modulated innate immune processes.
Altogether, our findings establish rTSMS as an effective non-invasive therapeutic approach capable of mitigating neuroinflammation and demyelination in inflammatory SCI, with marked sex-dependent outcomes. By identifying distinct immune mechanisms engaged in male and female mice, this study provides novel mechanistic insights into rTSMS action and supports its potential translational application in neuroinflammatory diseases.