Evidence map›Paper›PMID 41204337›Full record

ArticleJournal of neuroinflammation2025

Fatty acid-binding protein 4 drives microglia-mediated neuroinflammation through promoting S100A9 expression and lipid droplet accumulation after intracerebral hemorrhage.

Jiaqing He, Zijuan Qin, Haixiao Liu, Yaning Cai, Hao Wu, Tinghao Wang, Qing Hu, Yanni Xu, Pan Yang, Xun Wu and 2 more

Abstract read
In one paragraph

Article in Journal of neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. IL7R depletion mitigates neuroinflammation and ischemic stroke via AKT dephosphorylation dependent LCP1 suppression in mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Jiaqing He *Department of Neurosurgery, Xi'an Medical University, Xi'an, Shaanxi, 710021, China.
Zijuan Qin *School of Medicine, Northwest University, 229 Taibai North Road, Xi'an, 710069, China.
Haixiao Liu *Department of Neurosurgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Yaning CaiDepartment of Neurosurgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Hao WuDepartment of Orthopedics, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Tinghao WangDepartment of Neurosurgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Qing HuDepartment of Neurosurgery, First Affiliated Hospital of Gannan Medical University, Ganzhou City, 341000, China.
Yanni XuDepartment of Emergency, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Pan YangDepartment of Neurosurgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Xun WuDepartment of Neurosurgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. 2645302700@qq.com.
Yan QuDepartment of Neurosurgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. yanqu0123@fmmu.edu.cn.
Wei GuoDepartment of Neurosurgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. 18729985168@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAs primary immune sentinels of the central nervous system (CNS), microglia respond rapidly to acute brain injury and engage in dynamic crosstalk with infiltrating peripheral immune cells. This interplay critically shapes the neuroinflammatory microenvironment-a key determinant of secondary brain injury (SBI) following intracerebral hemorrhage (ICH). Fatty acid-binding protein 4 (FABP4), an adipokine associated with metabolic disorders, is recognized as a pivotal modulator of inflammatory responses; however, its role in ICH-induced SBI remains undefined.

objectivesTo investigate the pathogenic functions of FABP4 in microglia after ICH, elucidate its molecular mechanisms, and develop targeted therapeutic strategies.

methodsBlood and brain tissue samples from ICH patients were analyzed to evaluate the relationships between FABP4 expression and prognosis. Behavioral tests, Nissl staining, and Golgi-Cox staining were used to quantify neuronal damage. Immunofluorescence and flow cytometry were used to assess microglial activation and immune cell infiltration. Transcriptomic, proteomic, co-immunoprecipitation, western blotting, and ChIP‒qPCR analyses were used to examine the FABP4 regulatory network. Brain-targeted nanoparticles were engineered to deliver FABP4-specific siRNA.

resultsClinical analyses revealed microglia-specific FABP4 upregulation in ICH patients, correlating with poor neurological outcomes. Microglial Fabp4 knockout in mice attenuated neuronal loss, ameliorated cerebral edema, and enhanced functional recovery after ICH. Mechanistically, FABP4 promoted lipid droplet accumulation and inhibited the ubiquitin-proteasome-mediated degradation of S100A9 in microglia, synergistically amplifying neuroinflammation. Moreover, the activity of FABP4 in microglia facilitated neutrophil transendothelial migration into the brain parenchyma, exacerbating injury via the release of neutrophil extracellular traps (NETs). Finally, pharmacological FABP4 inhibition using brain-targeted nanoparticles conferred significant neuroprotective effects in ICH models.

conclusionThis study establishes that FABP4 acts as a novel orchestrator of post-ICH neuroinflammation through dual enzymatic and nonenzymatic pathways. We also demonstrate a targeted nanotherapeutic strategy to suppress FABP4 and improve neurological outcomes.

Indexed as

Calgranulin BCerebral HemorrhageFatty Acid-Binding ProteinsLipid DropletsMicrogliaNeuroinflammatory DiseasesAnimalsFemaleHumansMaleMiceMice, Inbred C57BLMice, KnockoutCalgranulin BFABP4 protein, humanFabp4 protein, mouseFatty Acid-Binding ProteinsS100A9 protein, humanS100A9 protein, mouseFABP4Intracerebral hemorrhageLipid dropletMicrogliaNeutrophilS100A9

Identifiers

PMID41204337
PMCPMC12595865

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.