{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T08:06:40Z","timestamp":1789718800814,"version":"4.0.1"},"reference-count":47,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Graduate Scholarship from USAID"},{"name":"Veterans Affairs Puget Sound Health Care System ACOS Research Fund"},{"DOI":"10.13039\/100001011","name":"The Joe W. and Dorothy Dorsett Brown Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001011","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Streptozotocin (STZ) is an alkylating agent that has neurotoxic effects when injected into the cerebral ventricles (ICV) and also models many other features of Alzheimer\u2019s disease. However, the mechanisms of STZ neurotoxicity are not well understood. In this study, we hypothesized that some of the neurotoxic effects of STZ could be due to direct activities on brain endothelial cells and astrocytes, which are key in forming and supporting the functions of the blood\u2013brain barrier (BBB), respectively. To test this hypothesis, we characterized the changes induced by STZ either in cultures of human-induced pluripotent stem cell (iPSC)-derived brain endothelial-like cells (iBECs), which form an in vitro BBB model, or in primary human astrocytes. We found that STZ at a dosage of 5 mM caused a delayed reduction in the transendothelial electrical resistance (TEER) of iBECs at 7\u201311 days post-treatment, indicating induction of BBB leakage. Additionally, we observed significant increases in albumin leakage across the monolayer, altered iBEC morphology, and reductions in tight junction proteins, suggesting that STZ causes BBB disruption. We further found that the BBB glucose transporter GLUT-1 was reduced in iBECs, as was the total number of iBECs. In astrocytes, the 5 mM dose of STZ reduced the GFAP signal and total number of cells, suggesting that STZ has anti-proliferative and\/or toxic effects on astrocytes. Together, these data support that STZ\u2019s neurotoxic effects could be due, in part, to its direct toxic activities on brain endothelial cells and astrocytes.<\/jats:p>","DOI":"10.3390\/cells14211745","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T17:51:43Z","timestamp":1762451503000},"page":"1745","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Streptozotocin Causes Blood\u2013Brain Barrier and Astrocytic Dysfunction In Vitro"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8620-2849","authenticated-orcid":false,"given":"Sarah A.","family":"Habib","sequence":"first","affiliation":[{"name":"Biochemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt"},{"name":"Pharmacology and Biochemistry Department, Faculty of Pharmacy, The British University in Egypt, El Sherouk City, Cairo 11837, Egypt"},{"name":"Drug Research and Development Group, Health Research Center of Excellence, The British University in Egypt, El Sherouk City, Cairo 11837, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6004-2590","authenticated-orcid":false,"given":"Mohamed M.","family":"Kamal","sequence":"additional","affiliation":[{"name":"Pharmacology and Biochemistry Department, Faculty of Pharmacy, The British University in Egypt, El Sherouk City, Cairo 11837, Egypt"},{"name":"Drug Research and Development Group, Health Research Center of Excellence, The British University in Egypt, El Sherouk City, Cairo 11837, Egypt"},{"name":"Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4617-4909","authenticated-orcid":false,"given":"Mohamed H.","family":"Aly","sequence":"additional","affiliation":[{"name":"Pharmacology and Biochemistry Department, Faculty of Pharmacy, The British University in Egypt, El Sherouk City, Cairo 11837, Egypt"},{"name":"Drug Research and Development Group, Health Research Center of Excellence, The British University in Egypt, El Sherouk City, Cairo 11837, Egypt"},{"name":"Institute of Physiology, Christian-Albrechts-University of Kiel, 24118 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4765-0353","authenticated-orcid":false,"given":"Heba R.","family":"Ghaiad","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherine M.","family":"Rizk","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0496-3619","authenticated-orcid":false,"given":"William A.","family":"Banks","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington, Harborview Medical Center, 325 9th Avenue, Seattle, WA 98104, USA"},{"name":"Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, 1660 S. Columbian Way, Seattle, WA 98108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2575-1594","authenticated-orcid":false,"given":"Michelle A.","family":"Erickson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington, Harborview Medical Center, 325 9th Avenue, Seattle, WA 98104, USA"},{"name":"Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, 1660 S. Columbian Way, Seattle, WA 98108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1159\/000524988","article-title":"Streptozotocin, 1982\u20132022: Forty Years from the FDA\u2019s Approval to Treat Pancreatic Neuroendocrine Tumors","volume":"112","author":"Capdevila","year":"2022","journal-title":"Neuroendocrinology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Badr, O.I., Kamal, M.M., El-Maraghy, S.A., and Ghaiad, H.R. (2024). The Effect of Diabetes Mellitus on Differentiation of Mesenchymal Stem Cells into Insulin-Producing Cells. Biol. Res., 57.","DOI":"10.1186\/s40659-024-00502-4"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Furman, B.L. (2021). Streptozotocin-Induced Diabetic Models in Mice and Rats. Curr. 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