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However, the capability of PBM for ischemic stroke needs to be further explored and its mechanisms of action remain currently unclear. The aim of the present research was to identify a treatment protocol capable of inducing neuroprotection and to investigate the molecular mechanisms activated by a dual-wavelength near infrared (NIR) laser source in an organotypic hippocampal slice model of hypoxia\/ischemia. Hippocampal slices were exposed to oxygen and glucose deprivation (OGD) for 30\u00a0min followed by NIR laser light (fluence 3.71, 7.42, or 14.84\u00a0J\/cm<jats:sup>2<\/jats:sup>; wavelengths 808\u00a0nm and 905\u00a0nm) delivered immediately or 30\u00a0min or 60\u00a0min after OGD, in order to establish a therapeutic window. Neuronal injury was assessed by propidium iodide fluorescence 24\u00a0h later. Our results show that NIR laser irradiation attenuates OGD neurotoxicity once applied immediately or 30\u00a0min after OGD. Western blot analysis of proteins involved in neuroinflammation (iNOS, COX-2, NFkB subunit p65, and Bcl-2) and in glutamatergic-mediated synaptic activity (vGluT1, EAAT2, GluN1, and PSD95) showed that the protein modifications induced by OGD were reverted by NIR laser application. Moreover, CA1 confocal microscopy revealed that the profound morphological changes induced by OGD were reverted by NIR laser radiation. In conclusion, NIR laser radiation attenuates OGD neurotoxicity in organotypic hippocampal slices through attenuation of inflammatory mechanisms. These findings shed light on molecular definition of NIR neuroprotective mechanisms, thus underlining the potential benefit of this technique for the treatment of cerebral ischemia.<\/jats:p>","DOI":"10.1007\/s12035-021-02496-6","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T06:02:51Z","timestamp":1627452171000},"page":"5383-5395","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["NIR Laser Photobiomodulation Induces Neuroprotection in an In Vitro Model of Cerebral Hypoxia\/Ischemia"],"prefix":"10.1007","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8448-6092","authenticated-orcid":false,"given":"Elisabetta","family":"Gerace","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Cialdai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elettra","family":"Sereni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Lana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Nosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Giovannini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Monici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Mannaioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,28]]},"reference":[{"key":"2496_CR1","unstructured":"The top 10 causes of death. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/the-top-10-causes-of-death. 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The experimental protocols were approved by the Animal Care Committee of the Department of Neuroscience, Psychology, Drug Research and Child Health (NeuroFarBa) (ETS no. 176) and the European Communities Council Directive of 24 November 1986 (86\/609\/EEC). The authors further attest that all efforts were made to minimize the number of animals used and their suffering.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}