Evidence map›Paper›PMID 41689206›Full record

ArticleCNS neuroscience & therapeutics2026

KCC2 Dysfunction Mediated by Microglial BDNF/TrkB Signaling Exacerbates Early Post-Stroke Seizure Susceptibility.

Jing Zhou, Benjamin H Wang, Jiangning Yu, Guoxiang Wang, Jingyi Cai, Mohan Yu, Kehua Chen, Li Wan, Xu Liu, Zhigang Yang and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
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.

Jing ZhouDepartment of Neurosurgery and Neurology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Biological Science, Zhongshan Hospital, Fudan University, Shanghai, China.ORCID https://orcid.org/0000-0001-7838-4831
Benjamin H WangDepartment of Neurosurgery and Neurology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Biological Science, Zhongshan Hospital, Fudan University, Shanghai, China.
Jiangning YuDepartment of Neurosurgery and Neurology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Biological Science, Zhongshan Hospital, Fudan University, Shanghai, China.
Guoxiang WangDepartment of Neurosurgery and Neurology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Biological Science, Zhongshan Hospital, Fudan University, Shanghai, China.
Jingyi CaiDepartment of Neurosurgery and Neurology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Biological Science, Zhongshan Hospital, Fudan University, Shanghai, China.ORCID https://orcid.org/0009-0007-6123-7553
Mohan YuDepartment of Neurosurgery and Neurology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Biological Science, Zhongshan Hospital, Fudan University, Shanghai, China.
Kehua ChenDepartment of Neurosurgery and Neurology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Biological Science, Zhongshan Hospital, Fudan University, Shanghai, China.
Li WanDepartment of Neurosurgery and Neurology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Biological Science, Zhongshan Hospital, Fudan University, Shanghai, China.
Xu LiuDepartment of Neurosurgery and Neurology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Biological Science, Zhongshan Hospital, Fudan University, Shanghai, China.
Zhigang YangDepartment of Neurosurgery and Neurology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Biological Science, Zhongshan Hospital, Fudan University, Shanghai, China.
Yulong WangDepartment of Rehabilitation, the First Affiliated Hospital of Shenzhen University/Shenzhen Second People's Hospital, Shenzhen, China.
Yun WangDepartment of Neurosurgery and Neurology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Biological Science, Zhongshan Hospital, Fudan University, Shanghai, China.

Funding

National Natural Science Foundation of China 31771188National Natural Science Foundation of China 32111530119National Natural Science Foundation of China 81971204Sanming Project of Medicine in Shenzen Municipality SZSM202111010Science, Technology and Innovation Commission of Shenzhen Municipality JCYJ20210324103409023Shanghai Municipal Science and Technology Major project 2018SHZDZX01Shenzhen Key Medical Discipline Construction Fund SZXK048Xiyuan Project of the Fudan University Undergraduate Research Opportunities Program 2021-2022Xiyuan Project of the Fudan University Undergraduate Research Opportunities Program FDUROP
6 · The paper itself

Abstract

backgroundPost-stroke seizures are a common and debilitating complication with limited therapeutic options, underscoring the need to identify novel molecular targets. Disruption of chloride homeostasis via impaired potassium chloride cotransporter 2 (KCC2) activity is a key driver of neuronal hyperexcitability. While microglia are a predominant source of brain-derived neurotrophic factor (BDNF) in the acute phase after brain injury, the role of microglial BDNF and its signaling in KCC2 dysregulation and early post-stroke seizure susceptibility remain poorly defined.

methodsUsing a middle cerebral artery occlusion-reperfusion (MCAO-R) mouse model and oxygen-glucose deprivation/reoxygenation (OGD/R) in hippocampal neurons, we assessed KCC2 function, neuronal excitability, and seizure susceptibility. Pharmacological tools, including the microglial inhibitor minocycline, the TrkB antagonist K252a, the loop diuretic furosemide (FUR), repurposed here as a KCC2-stabilizing agent, and the KCC2 activator CLP290, were employed. Techniques included immunofluorescence, Western blotting, patch-clamp electrophysiology, electroencephalography (EEG), and behavioral seizure assessment.

resultsMCAO-R and OGD/R significantly reduced membrane KCC2 expression, leading to a depolarizing shift in the GABA equilibrium potentials (E

conclusionOur findings identify microglia-derived BDNF/TrkB signaling as a critical upstream pathway mediating KCC2 dysfunction in early post-stroke seizure. Targeting this axis by inhibiting microglial activation, blocking TrkB, or directly enhancing KCC2 function with activators like CLP290 represents a promising therapeutic strategy for stroke-related epilepsy.

Indexed as

Brain-Derived Neurotrophic FactorMembrane GlycoproteinsMicrogliaReceptor, trkBSeizuresStrokeSymportersAnimalsCarbazolesCarboxylic AcidsFurosemideGlucoseHippocampusIndenesIndole AlkaloidsInfarction, Middle Cerebral ArteryBdnf protein, mouseBrain-Derived Neurotrophic FactorCarbazolesCarboxylic Acids((dihydroindenyl)oxy)alkanoic acidFurosemideGlucoseIndenesIndole AlkaloidsK Cl- CotransportersMembrane GlycoproteinsMinocyclineNtrk2 protein, mouseProtein-Tyrosine KinasesReceptor, trkBstaurosporine aglyconeSymportersBDNFchloride homeostasisischemic strokemicrogliapotassium‐chloride cotransporter 2seizuresTrkB

Identifiers

PMID41689206
PMCPMC12905008

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.