{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:58:53Z","timestamp":1792205933389,"version":"4.4.0"},"reference-count":37,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,10]],"date-time":"2023-12-10T00:00:00Z","timestamp":1702166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China Scholarship Council","award":["202006940016"],"award-info":[{"award-number":["202006940016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypoxia triggers reactive microglial inflammation and lipid droplet (LD) accumulation under stroke conditions, although the mutual interactions between these two processes are insufficiently understood. Hence, the involvement of transforming growth factor (TGF)-\u03b21 in inflammation and LD accumulation in cultured microglia exposed to hypoxia were analyzed herein. Primary microglia were exposed to oxygen-glucose deprivation (OGD) injury and lipopolysaccharide (LPS) stimulation. For analyzing the role of TGF-\u03b21 patterns under such conditions, a TGF-\u03b21 siRNA and an exogenous recombinant TGF-\u03b21 protein were employed. Further studies applied Triacsin C, an inhibitor of LD formation, in order to directly assess the impact of LD formation on the modulation of inflammation. To assess mutual microglia-to-neuron interactions, a co-culture model of these cells was established. Upon OGD exposure, microglial TGF-\u03b21 levels were significantly increased, whereas LPS stimulation yielded decreased levels. Elevating TGF-\u03b21 expression proved highly effective in suppressing inflammation and reducing LD accumulation in microglia exposed to LPS. Conversely, inhibition of TGF-\u03b21 led to the promotion of microglial cell inflammation and an increase in LD accumulation in microglia exposed to OGD. Employing the LD formation inhibitor Triacsin C, in turn, polarized microglia towards an anti-inflammatory phenotype. Such modulation of both microglial TGF-\u03b21 and LD levels significantly affected the resistance of co-cultured neurons. This study provides novel insights by demonstrating that TGF-\u03b21 plays a protective role against microglia-mediated neuroinflammation through the suppression of LD accumulation. These findings offer a fresh perspective on stroke treatment, suggesting the potential of targeting this pathway for therapeutic interventions.<\/jats:p>","DOI":"10.3390\/ijms242417329","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T03:25:31Z","timestamp":1702265131000},"page":"17329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["TGF-\u03b21 Decreases Microglia-Mediated Neuroinflammation and Lipid Droplet Accumulation in an In Vitro Stroke Model"],"prefix":"10.3390","volume":"24","author":[{"given":"Wenqiang","family":"Xin","sequence":"first","affiliation":[{"name":"Department of Neurology, University of G\u00f6ttingen Medical School, 37075 Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongli","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of G\u00f6ttingen Medical School, 37075 Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of G\u00f6ttingen Medical School, 37075 Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6020-8290","authenticated-orcid":false,"given":"Stefan T.","family":"Gerner","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Giessen Medical School, 35392 Giessen, Germany"},{"name":"Center for Mind, Brain and Behavior (CMBB), University of Marburg and Justus Liebig University, 35032 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Huber","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Giessen Medical School, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8905-3138","authenticated-orcid":false,"given":"Martin","family":"Juenemann","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Giessen Medical School, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9088-5695","authenticated-orcid":false,"given":"Marius","family":"Butz","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Giessen Medical School, 35392 Giessen, Germany"},{"name":"Heart and Brain Research Group, Kerckhoff Heart and Thorax Center, 61231 Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"B\u00e4hr","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of G\u00f6ttingen Medical School, 37075 Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagen B.","family":"Huttner","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Giessen Medical School, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten R.","family":"Doeppner","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of G\u00f6ttingen Medical School, 37075 Goettingen, Germany"},{"name":"Department of Neurology, University of Giessen Medical School, 35392 Giessen, Germany"},{"name":"Center for Mind, Brain and Behavior (CMBB), University of Marburg and Justus Liebig University, 35032 Giessen, Germany"},{"name":"Department of Anatomy and Cell Biology, Medical University of Varna, 9238 Varna, Bulgaria"},{"name":"Research Institute for Health Sciences and Technologies (SABITA), Medipol University, 100098 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.4252\/wjsc.v13.i8.1030","article-title":"Modulating poststroke inflammatory mechanisms: Novel aspects of mesenchymal stem cells, extracellular vesicles and microglia","volume":"13","author":"Xin","year":"2021","journal-title":"World J. 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