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Its disruption due to unbalanced blood glucose levels (hyper- and hypoglycemia) occurring in metabolic disorders, such as type 2 diabetes, can lead to neuroinflammation, and increase the risk of developing neurodegenerative diseases. One of the most studied natural anti-diabetic, anti-inflammatory, and neuroprotective compounds is resveratrol (RSV). It activates sirtuin 1 (SIRT1), a key metabolism regulator dependent on cell energy status. The aim of this study was to assess the astrocyte SIRT1 response to neuroinflammation and subsequent RSV treatment, depending on systemic glycemia. For this purpose, we used an optimized in vitro model of the BBB consisting of endothelial cells and astrocytes, representing microvascular and brain compartments (MC and BC), in different glycemic backgrounds. Astrocyte-secreted SIRT1 reached the highest concentration in hypo-, the lowest in normo-, and the lowest in hyperglycemic backgrounds. Lipopolysaccharide (LPS)-induced neuroinflammation caused a substantial decrease in SIRT1 in all glycemic backgrounds, as observed earliest in hyperglycemia. RSV partially counterbalanced the effect of LPS on SIRT1 secretion, most remarkably in normoglycemia. Our results suggest that abnormal glycemic states have a worse prognosis for RSV-therapy effectiveness compared to normoglycemia.<\/jats:p>","DOI":"10.3390\/ijms241411640","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T21:20:14Z","timestamp":1689801614000},"page":"11640","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Interplay between Systemic Glycemia and Neuroprotective Activity of Resveratrol in Modulating Astrocyte SIRT1 Response to Neuroinflammation"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1633-6345","authenticated-orcid":false,"given":"Anna D.","family":"Grabowska","sequence":"first","affiliation":[{"name":"Laboratory of the Blood-Brain Barrier, Department of Biophysics, Physiology and Pathophysiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"W\u0105troba","sequence":"additional","affiliation":[{"name":"Laboratory of the Blood-Brain Barrier, Department of Biophysics, Physiology and Pathophysiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Witkowska","sequence":"additional","affiliation":[{"name":"Laboratory of the Blood-Brain Barrier, Department of Biophysics, Physiology and Pathophysiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Mikulska","sequence":"additional","affiliation":[{"name":"Laboratory of the Blood-Brain Barrier, Department of Biophysics, Physiology and Pathophysiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8542-1706","authenticated-orcid":false,"given":"Nuno","family":"Sep\u00falveda","sequence":"additional","affiliation":[{"name":"Faculty of Mathematics and Information Science, Warsaw University of Technology, Koszykowa 75, 00-662 Warsaw, Poland"},{"name":"CEAUL\u2014Centro de Estat\u00edstica e Aplica\u00e7\u00f5es da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0124-060X","authenticated-orcid":false,"given":"Dariusz","family":"Szukiewicz","sequence":"additional","affiliation":[{"name":"Laboratory of the Blood-Brain Barrier, Department of Biophysics, Physiology and Pathophysiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"key":"ref_1","unstructured":"Nag, S., and Begley, D. 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