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Background: Non-invasive photobiomodulation therapy (PBMT), employing specific infrared light wavelengths to stimulate biological tissues, has recently gained attention for its application to treat neurological disorders. Here, we aimed to uncover the cellular targets of PBMT and assess its potential as a therapeutic intervention for multiple sclerosis (MS)., Methods: We applied daily dorsoventral PBMT in an experimental autoimmune encephalomyelitis (EAE) mouse model, which recapitulates key features of MS, and revealed a strong positive impact of PBMT on the sensorimotor deficits. To understand the cellular mechanisms underlying these striking effects, we used state-of-the-art tools and methods ranging from two-photon longitudinal imaging of triple fluorescent reporter mice to histological investigations and patch-clamp electrophysiological recordings., Results: We found that PBMT induced anti-inflammatory and neuroprotective effects in the dorsal spinal cord. PBMT prevented peripheral immune cell infiltration, glial reactivity, as well as the EAE-induced hyperexcitability of spinal interneurons, both in dorsal and ventral areas, which likely underlies the behavioral effects of the treatment. Thus, aside from confirming the safety of PBMT in healthy mice, our preclinical investigation suggests that PBMT exerts a systemic and beneficial effect on the physiopathology of EAE, primarily resulting in the modulation of the inflammatory processes., Conclusion: PBMT may therefore represent a new valuable therapeutic option to treat MS symptoms., Competing Interests: Declarations. Ethics approval and consent to participate: All experimental procedures were performed in accordance with the French legislation and in compliance with the European Community Council Directive of November 24, 1986 (86/609/EEC), for the care and use of laboratory animals. The research was authorized by the Direction Départementale des Services Vétérinaires des Bouches-du-Rhône (license D-13-055-21) and approved by the National Committee for Ethics in Animal Experimentation and the local ethics committee (Comité d’Ethique en Neurosciences INT-Marseille, CE71 Nb A1301404 [project authorization APAFIS#31909 and CE14 project authorization APAFIS#30760]). Competing interests: G. B. is a member of the company REGEnLIFE and owns equity. J. T. is a consultant for REGEnLIFE. V.E., D. R., G. R., R. B., and F.D. are members of AMU and declare that they have no financial interests that could be perceived as being a conflict of interest or to influence the work reported in this paper., (© 2024. The Author(s).)

Poor functional recovery after spinal cord injury (SCI) drives the development of novel strategies to manage this devastating condition. We recently showed promising immunomodulatory and pro-regenerative actions of bio-functionalized carbon microfibres (MFs) implanted in a rodent model of SCI. In order to maximize tissue repair while easing MF implantation, we produced a composite implant based on the embedding of several MFs within a fibrin hydrogel. We used intravital imaging of fluorescent reporter mice at the early stages and spinal sections of the same animals 3 months later to characterize the neuroinflammatory response to the implant and its impact on axonal regeneration. Whereas fibrin alone was inert in the first week, its enzymatic degradation drove the chronic activation of microglial cells and axonal degeneration within 3 months. However, the presence of MFs inside the fibrin hydrogel slowed down fibrin degradation and boosted the early recruitment of immune cells. Noteworthy, there was an enhanced contribution of monocyte-derived dendritic cells (moDCs), preceding a faster transition toward an anti-inflammatory environment with increased axonal regeneration over 3 months. The inclusion of MF here ensured the long-term biocompatibility of fibrin hydrogels, which would otherwise preclude successful spinal cord regeneration.