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We previously showed that photobiomodulation (PBM) significantly reduced the number of apoptotic cells in adult rat hippocampal organotypic slice cultures. In this study, we first optimized PBM delivery parameters for use in mTBI, conducting cadaveric studies to calibrate 660 and 810\u2009nm lasers for transcutaneous delivery of PBM to the cortical surface. We then used an in vivo weight drop mTBI model in adult rats and delivered daily optimized doses of 660, 810\u2009nm, or combined 660\/810\u2009nm PBM. Functional recovery was assessed using novel object recognition (NOR) and beam balance tests, whilst histology and immunohistochemistry were used to assess the mTBI neuropathology. We found that PBM at 810, 660\u2009nm, or 810\/660\u2009nm all significantly improved both NOR and beam balance performance, with 810\u2009nm PBM having the greatest effects. Histology demonstrated no overt structural damage in the brain after mTBI, however, immunohistochemistry using brain sections showed significantly reduced activation of both CD11b<jats:sup>+<\/jats:sup> microglia and glial fibrillary acidic protein (GFAP)<jats:sup>+<\/jats:sup> astrocytes at 3\u2009days post\u2010injury. Significantly reduced cortical localization of the apoptosis marker, cleaved caspase\u20103, and modest reductions in extracellular matrix deposition after PBM treatment, limited to choroid plexus and periventricular areas were also observed. Our results demonstrate that 810\u2009nm PBM optimally improved functional outcomes after mTBI, reduced markers associated with apoptosis and astrocyte\/microglial activation, and thus may be useful as a potential regenerative therapy.<\/jats:p>","DOI":"10.1002\/btm2.10727","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T07:20:26Z","timestamp":1728631226000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Photobiomodulation improves functional recovery after mild traumatic brain injury"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3222-133X","authenticated-orcid":false,"given":"Andrew R.","family":"Stevens","sequence":"first","affiliation":[{"name":"Neuroscience and Ophthalmology, Department of Inflammation and Ageing School of Infection, Inflammation and Immunology, University of Birmingham  Edgbaston Birmingham UK"},{"name":"NIHR 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