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Diet\u2010induced obesity leads to insulin resistance and subsequently, brain insulin deficiency. The purpose of this study was to investigate the potential impact of brain insulin deficiency on post\u2010stroke outcomes. To accomplish this, brain insulin levels were assessed in male C57BL\/6J (B6) mice placed on either a standard diet or 54% kcal high\u2010fat diet, a known model of insulin resistance. Mice were subjected to either a sham surgery (control) or 30\u2010min middle cerebral artery occlusion to induce an ischemic stroke and administered either intranasal saline (0.9%) or intranasal insulin (1.75\u2009U) twice daily for 5\u2009days beginning on day 1 post\u2010stroke. High\u2010fat diet\u2010induced brain insulin deficiency was associated with increased mortality, neurological and cognitive deficits. On the other hand, increasing brain insulin levels via intranasal insulin improved survival, neurological and cognitive function in high\u2010fat diet mice. Our data suggests that brain insulin deficiency correlates with worse post\u2010stroke outcomes in a diet\u2010induced mouse model of insulin resistance and increasing brain insulin levels may be a therapeutic target to improve stroke recovery.<\/jats:p>","DOI":"10.1002\/jnr.25237","type":"journal-article","created":{"date-parts":[[2023,8,12]],"date-time":"2023-08-12T01:26:19Z","timestamp":1691803579000},"page":"1757-1769","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Intranasal insulin helps overcome brain insulin deficiency and improves survival and post\u2010stroke cognitive impairment in male mice"],"prefix":"10.1002","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8518-3680","authenticated-orcid":false,"given":"Crystal J.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Neurology Medical University of South Carolina  Charleston South Carolina USA"},{"name":"Department of Neurosciences Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8886-1638","authenticated-orcid":false,"given":"Serena\u2010Kaye","family":"Sims","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of South Carolina  Charleston South Carolina USA"},{"name":"Department of Biology College of Charleston  Charleston South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacy","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4463-2443","authenticated-orcid":false,"given":"Alexus","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taylor","family":"McLeod","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of South Carolina  Charleston South Carolina USA"},{"name":"Department of Public Health Sciences Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4776-5839","authenticated-orcid":false,"given":"Catrina","family":"Sims\u2010Robinson","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of South Carolina  Charleston South Carolina USA"},{"name":"Department of Neurosciences Medical University of South Carolina  Charleston South Carolina USA"},{"name":"Ralph H. 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