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We use microglial state programs as an organizing axis for WM injury-to-repair logic, while emphasizing that WM outcomes are multicellular and involve oligodendrocyte-lineage cells, astrocytes, axons\/neurons, and vascular factors. Microglia span an injury\u2013repair continuum, from inflammatory programs that increase oxidative stress and debris burden to repair-competent programs that support debris handling, remyelination, and axonal integrity. Near-infrared photobiomodulation (PBM; ~800\u20131100\u00a0nm) is most consistently associated with modulation of mitochondrial redox\/bioenergetic pathways and inflammatory tone. CCO-centered mechanistic framing is best established near ~\u2009800\u2013850\u00a0nm, whereas longer wavelengths (e.g., ~\u20091064\u20131070\u00a0nm) may involve additional initiating mechanisms with downstream convergence on shared redox\/bioenergetic and inflammatory pathways. Across demyelination and spinal cord injury models, appropriately dosed PBM has been reported to reduce inflammatory glial readouts and to associate with improved myelin\/axon-related endpoints and functional measures, although mechanistic certainty varies across models. Human evidence remains early but broadly supports safety; a randomized trial in moderate traumatic brain injury reported treatment-related changes in diffusion-MRI WM metrics, while small dementia and chronic-injury studies report heterogeneous cognitive and physiological signals. Given dose dependence and depth-limited transcranial delivery, we synthesize mechanism-informed, dose-aware reporting guidance and WM-anchored outcome frameworks that pair diffusion MRI\/DTI with interpretable biomarkers (e.g., NfL, GFAP, sTREM2) and thermally controlled sham designs. We also note potential indirect\/systemic contributions that could help reconcile depth\u2013dose constraints with deeper WM effects.<\/jats:p>","DOI":"10.1007\/s12017-026-08924-x","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T12:12:45Z","timestamp":1782821565000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Near\u2011Infrared Photobiomodulation in White\u2011Matter Disease: From Microglial States to Measurable Endpoints"],"prefix":"10.1007","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1017-1826","authenticated-orcid":false,"given":"Jiahao","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanguang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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