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Moncomble, L.

Publications and source records attributed to Moncomble, L..

3 recordsLinked to original sources

Pattern-dependent low-intensity repetitive magnetic stimulation enhances spinal cord repair through modulation of neuroinflammation

Spinal cord injuries (SCI) are traumatic lesions of the spinal cord that commonly result from physical trauma. They can lead to severe and permanent impairments in motor, sensory, and/or autonomic functions, often resulting in paraplegia or tetraplegia. Despite advances in this field, effective restorative treatments for SCI remain limited. Over the past few years, several therapeutic strategies have been investigated to promote functional recovery after SCI, including neuromodulation approaches. Repetitive magnetic stimulation has emerged as a promising non-invasive strategy, with encouraging results when the stimulation is applied directly over the spinal cord. However, most studies have focused on high-intensity stimulation, while the key parameters underlying its therapeutic efficacy remain poorly understood. In this study, we investigated the effects of low-intensity repetitive trans-spinal magnetic stimulation (LI-rTSMS) following SCI in mice, using BMS, histological and RNA sequencing approaches. We aimed to determine the optimal protocol by comparing three stimulation patterns (10 Hz, iTBS and BHFS) and two coil sizes. Our results show that LI-rTSMS modulates the injured spinal cord in a pattern- and coil size-dependent manner, with distinct effects on fibrotic, neural, and inflammatory responses. Notably, the BHFS pattern produced the most marked tissue-remodeling effects, reducing fibrosis, reactive astrogliosis, and phagocytosis of myelin debris. This reduction in phagocytosis was also observed with a smaller coil, supporting an effect of LI-rTSMS on this process. We also identified distinct inflammatory signatures depending on the stimulation pattern and time after injury. Transcriptomic analyses revealed a common early inflammatory response to LI-rTSMS, whereas each stimulation pattern subsequently led to distinct molecular signatures after 2 weeks stimualtion. In addition, ependymal cells are known to retain endogenous regenerative potential following SCI. We found that LI-rTSMS increased ependymal cell proliferation and migration toward the lesion site, without detectable changes in their differentiation. Finally, we assessed c-Fos expression as a marker of early transcriptional changes in neurons. LI-rTSMS did not result in significant changes, suggesting that the observed effects were unlikely to be mediated by early, widespread neuronal activation. Altogether, this study provides mechanistic insights into the pattern-dependent effects of LI-rTSMS and highlights its potential role for future clinical translation.

neuroscience↗

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 such as transverse myelitis (TM), are characterized by severe neuroinflammation, demyelination, and long-term disabilities. Current treatments remain limited, highlighting the need for novel non-invasive therapeutic approaches. Repetitive magnetic stimulation (RMS) has emerged as a promising strategy, but its mechanisms and efficacy in inflammatory contexts remain poorly described. Here, we investigated the effects of RMS applied as trans-spinal RMS (rTSMS) in a mouse model of focal spinal cord demyelination induced by lysophosphatidylcholine (LPC). When applied one day after LPC injection, rTSMS reduced inflammation, demyelination, and fibroglial scar formation, while promoting early locomotor recovery in both sexes. In contrast, when treatment was initiated three days after LPC injection, corresponding to the peak of motor deficits, rTSMS conferred tissue protection and functional benefits only in female mice. RNA sequencing analyses revealed sex-dependent immune modulation: in females, rTSMS primarily regulated adaptive T cell-related pathways, whereas in males, it mainly targeted innate immune responses such as neutrophil activity and phagocytosis. Complementary in vitro experiments using microglial and macrophage cultures further demonstrated that RMS modulates transcriptomic responses differently depending on cell type and inflammatory state. Specifically, RMS attenuated IL-1-induced pro-inflammatory signaling in macrophages and completely abolished these effects in microglia. Altogether, our findings establish rTSMS as a non-invasive therapy capable of reducing neuroinflammation and demyelination in inflammatory SCI, with pronounced sex-dependent effects. By uncovering distinct immune pathways engaged in male and female mice, this study provides mechanistic insights into rTSMS action and opens perspectives for its translational use in neuroinflammatory diseases.

neuroscience↗

Spinal cord injury: What are the lesion effects on transplanted cells in an autograft model?

AbstractSpinal cord injury (SCI) is a serious pathology of the central nervous system that results in loss of motor, sensory and autonomic functions below the level of the lesion and for which, unfortunately, there is currently no cure. In addition to the loss of function, SCI induces a systemic inflammation that is not confined to the spinal cord and whose effects are increasingly well characterized. In particular, SCI causes cerebral inflammation, which is responsible for the impairment of hippocampal and bulbar neurogenesis. Many therapies have been tested as potential treatments for SCI. In animal models, cell therapies have shown interesting effects such as spinal scar reduction, anti-inflammatory properties, axonal regrowth or neuronal survival, allowing better functional recovery. However, in human studies, their therapeutic capacities are less significant. Beyond obvious differences in pathophysiology and cell culture procedures, a key paradigm of cell transplantation differs between humans and animals. In animal models, transplanted cells are systematically taken from healthy individuals, whereas in humans the immune incompatibility leads to the realization of autologous transplantation. Therefore, we were interested in the lesion effects on the neuro-repairing potential of olfactory ensheathing cells (OECs) harvested from olfactory bulbs. Using functional sensory-motor studies, histological and gene expression analyses, we were able to demonstrate for the first time that the lesion negatively affects the therapeutic properties of cells used to treat SCI. These innovative results shed new light on the future use of cell transplantation in autologous transplantation after SCI.

neuroscience↗