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The present work evaluated the preventative effect of photobiomodulation (PBM) preconditioning, and its underlying mechanism of action on brain damage in an HI model in neonatal rats. According to the optimal time response of ATP levels in brain samples removed from normal rats, a PBM preconditioning (PBM\u2010P) regimen (808\u2009nm CW laser, 1\u2009cm<jats:sup>2<\/jats:sup> spot, 100\u2009mW\/cm<jats:sup>2<\/jats:sup>, 12\u2009J\/cm<jats:sup>2<\/jats:sup>) was delivered to the scalp 6\u2009hours before HI. PBM\u2010P significantly attenuated cognitive impairment, volume shrinkage in the brain, neuron loss, dendritic and synaptic injury after HI. Further mechanistic investigation found that PBM\u2010P could restore HI\u2010induced mitochondrial dynamics and inhibit mitochondrial fragmentation, followed by a robust suppression of cytochrome c release, and prevention of neuronal apoptosis by inhibition of caspase activation. Our work suggests that PBM\u2010P can attenuate HI\u2010induced brain injury by maintaining mitochondrial dynamics and inhibiting the mitochondrial apoptotic pathway.<\/jats:p><jats:p><jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/jbio201800359-gra-0001.png\" xlink:title=\"image\"\/><\/jats:p>","DOI":"10.1002\/jbio.201800359","type":"journal-article","created":{"date-parts":[[2019,1,17]],"date-time":"2019-01-17T04:46:30Z","timestamp":1547700390000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Photobiomodulation preconditioning prevents cognitive impairment in a neonatal rat model of hypoxia\u2010ischemia"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5671-3750","authenticated-orcid":false,"given":"Luodan","family":"Yang","sequence":"first","affiliation":[{"name":"Laboratory of Laser Sports Medicine, College of Physical Education and Sports Science South China Normal University  Guangzhou China"},{"name":"Department of Neuroscience &amp; Regenerative Medicine Medical College of Georgia, Augusta University  Augusta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Neuroscience &amp; Regenerative Medicine Medical College of Georgia, Augusta University  Augusta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongyun","family":"Wu","sequence":"additional","affiliation":[{"name":"Laboratory of Laser Sports Medicine, College of Physical Education and Sports Science South China Normal University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neuroscience &amp; Regenerative Medicine Medical College of Georgia, Augusta University  Augusta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichen","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience &amp; Regenerative Medicine Medical College of Georgia, Augusta University  Augusta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baocheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience &amp; Regenerative Medicine Medical College of Georgia, Augusta University  Augusta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Zong","sequence":"additional","affiliation":[{"name":"Department of Neuroscience &amp; Regenerative Medicine Medical College of Georgia, Augusta University  Augusta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Hamblin","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital  Boston Massachusetts"},{"name":"Department of Dermatology Harvard Medical School  Boston Massachusetts"},{"name":"Harvard\u2010MIT Division of Health Sciences and Technology  Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timon C.\u2010Y.","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Laser Sports Medicine, College of Physical Education and Sports Science South China Normal University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6499-7952","authenticated-orcid":false,"given":"Quanguang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Laser Sports Medicine, College of Physical Education and Sports Science South China Normal University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.93"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2003.11.002"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2013.09.004"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61835-8"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/jp.2010.91"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-007-0437-8"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2013.07.001"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3604"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18020265"},{"key":"e_1_2_7_11_1","first-page":"1","volume":"2","author":"Lu Y.","year":"2015","journal-title":"J. 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