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This study aimed to evaluate whether photobiomodulation can enhance regeneration of crushed facial nerves and attempt to investigate the possible underlying mechanism of neuroprotective function and therapeutic target. Various parameters of photobiomodulation were assigned to the facial nerves and Schwann cells (SCs) separately during crushed injury in rats. Axonal regeneration, functional outcomes, and SC apoptosis, proliferation, and underlying mechanisms of action were evaluated by morphological, histopathological, and functional assessments, flow cytometry, western blotting, real-time PCR, and IncuCyte. The results showed that photobiomodulation improved axonal regeneration and functional recovery, and also promoted proliferation, and inhibited apoptosis of SCs, both of these were considered as the most effective parameters in 250mW group. In addition, the neuroprotective effects of photobiomodulation (500mW) were likely associated with oxidative stress\u2013induced SC apoptosis via activation of the PI3K\/Akt signaling pathway. Our results revealed that photobiomodulation significantly promoted axonal regeneration, functional recovery, and regeneration of the facial nucleus, and its mechanism was related to the up-regulation of the PI3K\/Akt signaling pathway. These findings provide clear experimental evidence of photobiomodulation as an alternative therapeutic strategy for peripheral nerve damage.<\/jats:p>","DOI":"10.1007\/s10103-021-03344-8","type":"journal-article","created":{"date-parts":[[2021,7,24]],"date-time":"2021-07-24T05:03:00Z","timestamp":1627102980000},"page":"993-1006","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Photobiomodulation enhances facial nerve regeneration via activation of PI3K\/Akt signaling pathway\u2013mediated antioxidant response"],"prefix":"10.1007","volume":"37","author":[{"given":"Bohan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,24]]},"reference":[{"key":"3344_CR1","doi-asserted-by":"crossref","unstructured":"Andraus RAC, Maia LP, de Souza Lino AD, Fernandes KBP, de Matos Gomes MV, de Jesus Guirro RR, Barbieri CH (2017) LLLT actives MMP-2 and increases muscle mechanical resistance after nerve sciatic rat regeneration. 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