Evidence mapPaperPMID 40277259Full record

ArticleCNS neuroscience & therapeutics2025

Balancing Anti-Inflammation and Neurorepair: The Role of Mineralocorticoid Receptor in Regulating Microglial Phenotype Switching After Traumatic Brain Injury.

Bin Zhang, Miao Bai, Mengshi Yang, Yumei Wang, Xueling Zhang, Xiyu Chen, Min Gao, Baiyun Liu, Guangzhi Shi

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Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Bin ZhangDepartment of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Miao BaiDepartment of Neurology, The First Hospital of Tsinghua University, Beijing, China.
Mengshi YangDepartment of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Yumei WangDepartment of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Xueling ZhangDepartment of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Xiyu ChenDepartment of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Min GaoDepartment of Animal Laboratory, Beijing Neurosurgical Institute, Beijing, China.
Baiyun LiuDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Guangzhi ShiDepartment of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.ORCID 0000-0003-4189-5800

Funding

Beijing Science and Technology Planning Project Z201100005520039Natural Science Foundation of Capital Medical University PYZ23123
6 · The paper itself

Abstract

backgroundAs potent anti-inflammatory agents, glucocorticoids (GCs) have been widely used in the treatment of traumatic brain injury (TBI). However, their use remains controversial. Our previous study indicated that although dexamethasone (DEX) exerted anti-inflammatory effects and protected the blood-brain barrier (BBB) by activating the glucocorticoid receptor (GR) after TBI, it also impeded tissue repair processes due to excessive anti-inflammation. 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.

objectiveThis study aimed to explore the impact of the MR agonist fludrocortisone on microglia polarization, angiogenesis, functional rehabilitation, and associated mechanisms after TBI.

methodsWe established a mice controlled cortical impact model, and then immunofluorescence staining, western blot, rt-PCR, 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.

resultsOur 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/PPARγ pathway. Additionally, the PI3K/Akt/HIF-1α pathway was involved in VEGF expression and in the process of angiogenesis.

conclusionFludrocortisone, the specific MR agonist, exerted anti-neuroinflammatory 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.

Indexed as

Anti-Inflammatory AgentsBrain Injuries, TraumaticFludrocortisoneMicrogliaReceptors, MineralocorticoidAnimalsMaleMiceMice, Inbred C57BLNeuroinflammatory DiseasesPhenotypeAnti-Inflammatory AgentsFludrocortisoneReceptors, Mineralocorticoidfludrocortisonemineralocorticoid receptor microglia polarizationneuroinflammationtraumatic brain injury

Identifiers

PMID40277259
PMCPMC12023002

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.