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Due to the presence of a basal stem cell niche, the adult mammalian OE is a dynamic tissue capable of replacing neurons following their loss. Nonetheless, certain conditions, such as blunt head trauma, can result in persistent olfactory loss, thought to be due to shearing of olfactory nerve filaments at the skull base, degeneration, and failures in proper regeneration\/reinnervation. The identification of new treatment strategies aimed at preventing degeneration of olfactory neurons is, therefore, needed. In considering potential therapies, we have focused on N\u2010acetylcysteine (NAC), a glutathione substrate shown to be neuroprotective, with a record of safe clinical use. Here, we have tested the use of NAC in an animal model of olfactory degeneration. Administered acutely, we found that NAC (100\u2009mg\/kg, twice daily) resulted in a reduction of olfactory neuronal loss from the OE of the nose following surgical ablation of the olfactory bulb. At 1\u2009week postlesion, we identified 54\u2009\u00b1\u20098.1 mature neurons per 0.5 mm epithelium in NAC\u2010treated animals vs. 28\u2009\u00b1\u20094.2 in vehicle\u2010treated controls (<jats:italic>P<\/jats:italic>\u2009=\u20090.02). Furthermore, in an olfactory cell culture model, we have identified significant alterations in the expression of several genes involved in oxidative stress pathways following NAC exposure. Our results provide evidence supporting the potential therapeutic utility for NAC acutely following head trauma\u2010induced olfactory loss. Anat Rec, 303:626\u2013633, 2020. \u00a9 2019 American Association for Anatomy<\/jats:p>","DOI":"10.1002\/ar.24066","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T07:35:10Z","timestamp":1547192110000},"page":"626-633","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Acute N\u2010Acetylcysteine Administration Ameliorates Loss of Olfactory Neurons Following Experimental Injury <i>In Vivo<\/i>"],"prefix":"10.1002","volume":"303","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3330-0918","authenticated-orcid":false,"given":"Stefania","family":"Goncalves","sequence":"first","affiliation":[{"name":"Department of Otolaryngology University of Miami Miller School of Medicine  Miami FL 33136 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9612-1696","authenticated-orcid":false,"given":"Bradley 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