Evidence mapPaperPMID 36898766Full record

ArticleAnnals of the rheumatic diseases2023

Microglia activation in the presence of intact blood-brain barrier and disruption of hippocampal neurogenesis via IL-6 and IL-18 mediate early diffuse neuropsychiatric lupus.

Dionysis Nikolopoulos, Theodora Manolakou, Alexia Polissidis, Anastasia Filia, George Bertsias, Yassemi Koutmani, Dimitrios T Boumpas

Open access · hybridAbstract read
In one paragraph

Article in Annals of the rheumatic diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
12.8field-weighted citation impact, top 1% of its field
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

70 citing papers in PubMed, 104 citations in OpenAlex.

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  8. Metabolic Reprogramming of Microglia in Neuroinflammation and Depression.International journal of molecular sciences · 2026
    Review
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  12. The spleen-brain axis in Alzheimer's disease and related dementias: Integrating immune and metabolic regulation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
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10 more citing papers are in PubMed but not listed here.

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

7 authors at 4 institutions in 2 countries.

Dionysis NikolopoulosCenter of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece dsnikolopoulos@gmail.com boumpasd@uoc.gr.ORCID 0000-0002-9894-6966
Theodora ManolakouCenter of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.ORCID 0000-0001-5284-6655
Alexia PolissidisBiomedical Research Foundation of the Academy, Athens, Greece.
Anastasia FiliaCenter of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
George BertsiasLaboratory of Autoimmunity-Inflammation, Institute of Molecular Biology and Biotechnology, Heraklion, Greece.
Yassemi KoutmaniBiomedical Research Foundation of the Academy, Athens, Greece.
Dimitrios T BoumpasCenter of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece dsnikolopoulos@gmail.com boumpasd@uoc.gr.ORCID 0000-0002-9812-4671
National and Kapodistrian University of Athens · GRBiomedical Research Foundation of the Academy of Athens · GRAcademy of Athens · GRUniversity of Crete · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionInflammatory mediators are detected in the cerebrospinal fluid of systemic lupus erythematosus patients with central nervous system involvement (NPSLE), yet the underlying cellular and molecular mechanisms leading to neuropsychiatric disease remain elusive.

methodsWe performed a comprehensive phenotyping of NZB/W-F1 lupus-prone mice including tests for depression, anxiety and cognition. Immunofluorescence, flow cytometry, RNA-sequencing, qPCR, cytokine quantification and blood-brain barrier (BBB) permeability assays were applied in hippocampal tissue obtained in both prenephritic (3-month-old) and nephritic (6-month-old) lupus mice and matched control strains. Healthy adult hippocampal neural stem cells (hiNSCs) were exposed

resultsAt the prenephritic stage, BBB is intact yet mice exhibit hippocampus-related behavioural deficits recapitulating the human diffuse neuropsychiatric disease. This phenotype is accounted by disrupted hippocampal neurogenesis with hiNSCs exhibiting increased proliferation combined with decreased differentiation and increased apoptosis in combination with microglia activation and increased secretion of proinflammatory cytokines and chemokines. Among these cytokines, IL-6 and IL-18 directly induce apoptosis of adult hiNSCs ex vivo. During the nephritic stage, BBB becomes disrupted which facilitates immune components of peripheral blood, particularly B-cells, to penetrate into the hippocampus further augmenting inflammation with locally increased levels of IL-6, IL-12, IL-18 and IL-23. Of note, an interferon gene signature was observed only at nephritic-stage.

conclusionAn intact BBB with microglial activation disrupting the formation of new neurons within the hippocampus represent early events in NPSLE. Disturbances of the BBB and interferon signature are evident later in the course of the disease.

Indexed as

Lupus Erythematosus, SystemicLupus Vasculitis, Central Nervous SystemAdultAnimalsBlood-Brain BarrierCytokinesHippocampusHumansInfantInterferonsInterleukin-18Interleukin-6MiceMicrogliaNeurogenesisCytokinesInterferonsInterleukin-18Interleukin-6AutoimmunityCytokinesLupus Erythematosus, Systemic

Identifiers

PMID36898766
PMCPMC10176423
OpenAlexW4323832150

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.