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Lipid droplet (LD) accumulation in microglia results in a dysfunctional and pro\u2010inflammatory state in the aged brain and worsens the outcome of neuroinflammatory and neurodegenerative diseases. However, the role of LD\u2010rich microglia (LDRM) under stroke conditions is unknown. Using in vitro and in vivo stroke models, herein accumulation patterns of microglial LD and their corresponding microglial inflammatory signaling cascades are studied. Interactions between temporal and spatial dynamics of lipid profiles and microglial phenotypes in different post\u2010stroke brain regions are found. Hence, microglia display enhanced levels of LD accumulation and elevated perilipin 2 (PLIN2) expression patterns when exposed to hypoxia or stroke. Such LDRM exhibit high levels of TNF\u2010\u03b1, IL\u20106, and IL\u20101\u03b2 as well as a pro\u2010inflammatory phenotype and differentially expressed lipid metabolism\u2010related genes. These post\u2010ischemic alterations result in distinct lipid profiles with spatial and temporal dynamics, especially with regard to cholesteryl ester and triacylglycerol levels, further exacerbating post\u2010ischemic inflammation. The present study sheds new light on the dynamic changes of brain lipid profiles and aggregation patterns of LD in microglia exposed to ischemia, demonstrating a mutual mechanism between microglial phenotype and function, which contributes to progression of brain injury.<\/jats:p>","DOI":"10.1002\/advs.202306863","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T01:41:11Z","timestamp":1725932471000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Dynamic Brain Lipid Profiles Modulate Microglial Lipid Droplet Accumulation and Inflammation Under Ischemic Conditions in Mice"],"prefix":"10.1002","volume":"11","author":[{"given":"Wei","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Neurology University Medicine G\u00f6ttingen (UMG) University of G\u00f6ttingen 37075 G\u00f6ttingen Germany"},{"name":"Department of Neurology The Affiliated Hospital of Southwest Jiaotong University &amp; 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