{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:30:00Z","timestamp":1786681800811,"version":"build-2736575974"},"reference-count":85,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["25-25-00294"],"award-info":[{"award-number":["25-25-00294"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"award":["25-25-00294"],"award-info":[{"award-number":["25-25-00294"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>In rats with transient global ischemia of forebrain, the intranasal administration of 0.6 \u00b5g of IGF-1 or 0.6 IU (equal to 24 \u00b5g) of insulin 1 h before or 2 h after (but not 30 min after) the ischemic episode and then daily during 7 days of reperfusion diminished the death of neurons in CA1 region of hippocampus to the levels observed in this region of sham-operated rats. The intracerebroventricular administration of autophagy and apoptosis inhibitors (3-MA and Z-VAD-FMK, respectively) markedly increased the viability of neurons in hippocampal CA1 region, providing evidence that autophagic and apoptotic deaths of neurons predominate in this brain region of rats subjected to forebrain ischemia and reperfusion, while intranasal administration of IGF-1 and insulin are able to diminish or prevent autophagic and apoptotic death of neurons. To confirm such conclusion, we showed that intranasal administration of insulin or IGF-1 prevented the increase in the level of such autophagy markers as LCB3-II and pULK-1(Ser555) in the hippocampus of ischemic and reperfused brain; other data confirming the ability of IGF-1 and insulin to inhibit autophagic processes and caspase-3 activity were also obtained. IGF-1 and insulin were shown to prevent the activation of microglia and astroglia and neuroinflammation in hippocampus of ischemic and reperfused forebrain. The similarity of IGF-1 and insulin effects suggests that insulin in much higher doses than IGF-1 is able to interact not only with insulin receptors, but also with IGF-1 receptors. As oncogenic effects are characteristic of IGF-1, insulin appears to be a better candidate for use in clinics.<\/jats:p>","DOI":"10.3390\/ijms27167183","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T13:46:16Z","timestamp":1786455976000},"page":"7183","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intranasal Administration of Insulin and IGF-1 Protects Hippocampal CA1 Neurons Against Transient Global Forebrain Ischemia by Inhibiting Autophagy, Apoptosis and Neuroinflammation: A Comparative Study"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8857-7012","authenticated-orcid":false,"given":"Irina O.","family":"Zakharova","sequence":"first","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Thorez av. 44, 194223 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5543-8657","authenticated-orcid":false,"given":"Liubov V.","family":"Bayunova","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Thorez av. 44, 194223 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7390-888X","authenticated-orcid":false,"given":"Daria K.","family":"Avrova","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Thorez av. 44, 194223 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3337-1441","authenticated-orcid":false,"given":"Natalia F.","family":"Avrova","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Thorez av. 44, 194223 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","unstructured":"(2020). 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