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However, their use remains controversial. Our previous study indicated that although dexamethasone (DEX) exerted anti\u2010inflammatory effects and protected the blood\u2013brain barrier (BBB) by activating the glucocorticoid receptor (GR) after TBI, it also impeded tissue repair processes due to excessive anti\u2010inflammation. Conversely, fludrocortisone, acting as a specific mineralocorticoid receptor (MR) agonist, has shown potential in controlling neuroinflammation and promoting neurorepair, but the underlying mechanisms need further exploration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to explore the impact of the MR agonist fludrocortisone on microglia polarization, angiogenesis, functional rehabilitation, and associated mechanisms after TBI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We established a mice controlled cortical impact model, and then immunofluorescence staining, western blot, rt\u2010PCR, and MRI were performed to investigate microglia polarization, angiogenesis, and brain edema in the ipsilateral hemisphere after TBI and fludrocortisone treatment. Subsequently, functional tests including morris water maze, sucrose preference test, and forced swimming test were conducted to evaluate the effects of fludrocortisone treatment on neurofunction after TBI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results revealed that fludrocortisone suppressed neuroinflammation, enhanced angiogenesis and neuronal survival, and promoted functional rehabilitation by inducing a shift in microglia phenotype from M1 to M2 via the JAK\/STAT6\/PPAR\u03b3 pathway. Additionally, the PI3K\/Akt\/HIF\u20101\u03b1 pathway was involved in VEGF expression and in the process of angiogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Fludrocortisone, the specific MR agonist, exerted anti\u2010neuroinflammatory and neuroprotective effects by regulating phenotypic switching of microglia from M1 to M2 rather than suppressing all types of microglia. Our study provided a theoretical basis for the therapeutic strategy of GCs targeting neuroinflammation after TBI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70404","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T08:06:28Z","timestamp":1745568388000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Balancing Anti\u2010Inflammation and Neurorepair: The Role of Mineralocorticoid Receptor in Regulating Microglial Phenotype Switching After Traumatic Brain Injury"],"prefix":"10.1111","volume":"31","author":[{"given":"Bin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, Beijing Tiantan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Hospital of 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