Evidence map›Paper›PMID 42501052›Full record

ArticleAnnals of clinical and translational neurology2026

Intracerebral Hemorrhage Induces Monocyte TNF Signaling in Patients That Is Suppressed by BAF312.

Jonathan Howard DeLong, Sebastian Díaz-Pérez, Kevin Navin Sheth, Jang-Ho Cha, C J Malanga, Patricia G M Wagner, Nicole Pezous, Aurelie Hanin, Kyle B Walsh, H E Hinson and 1 more

Abstract read
In one paragraph

Article in Annals of clinical and translational neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Jonathan Howard DeLongDepartment of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA.ORCID https://orcid.org/0000-0002-2032-8228
Sebastian Díaz-PérezDepartment of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
Kevin Navin ShethDepartment of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA.ORCID https://orcid.org/0000-0003-2003-5473
Jang-Ho ChaNovartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA.ORCID https://orcid.org/0000-0002-0458-3931
C J MalangaNovartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA.
Patricia G M WagnerNovartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA.
Nicole PezousNovartis Pharma AG, Basel, Switzerland.
Aurelie HaninDepartment of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA.
Kyle B WalshDepartment of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
H E HinsonZuckerberg San Francisco General Hospital, University of California, San Francisco, California, USA.
Lauren Hachmann SansingDepartment of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA.ORCID https://orcid.org/0000-0002-6898-1680

Funding

Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI Eric P. Winer · 1985 to 2026
$85.0M
Vascular Training GrantT32HL007950 · NHLBI · YALE UNIVERSITY · PI JEFFREY R. BENDER, Daniel Greif · 2000 to 2026
$9.6M
High Performance Computing Instrumentation for the Yale Center for Genome AnalysisS10OD030363 · OD · YALE UNIVERSITY · PI MANE, SHRIKANT M · 2022 to 2022
$1.2M
American Heart Association 19EIA34770133American Heart Association 830877NCI NIH HHS P30 CA016359NHLBI NIH HHS T32 HL007950NIH HHS 1S10OD030363-01A1NIH HHS P30 CA016359NIH HHS S10 OD030363NIH HHS T32HL007950
6 · The paper itself

Abstract

objectiveIntracerebral hemorrhage (ICH) causes high morbidity and mortality, with neurotoxic inflammation driven by infiltrating monocytes. This study is an in-depth longitudinal examination of the immune response during the first week of ICH in the presence and absence of the immunomodulatory drug BAF312 (Siponimod).

methodsWe performed single-cell RNA sequencing on peripheral blood samples taken 1, 3, and 7 days post-ICH in patients treated with BAF312 (5 patients) or placebo (2 patients). The correlation of gene expression with time, drug treatment, measures of ICH severity, and clinical outcome was examined. Results were validated by comparison with previous studies and measurement of plasma cytokine concentration.

resultsA broad peripheral inflammatory response involving both lymphoid and myeloid cells peaked at day 3 post ICH. BAF312 markedly reduced peripheral blood T and B lymphocyte numbers by day 3. BAF312 also impacted the myeloid response, suppressing TNF signaling in classical and nonclassical monocytes. Multiple cytokine signaling pathways were decreased, though BAF312 did not impact plasma cytokine or chemokine concentrations. Surprisingly, increased monocyte TNF signaling was associated with better 90-day clinical outcome.

interpretationThese findings demonstrate broad peripheral leukocyte activation after ICH and suggest that during ICH, BAF312 suppresses both lymphoid and myeloid responses. The positive association of monocyte TNF signaling with better outcome points to the positive role of monocytes during the subacute stage of ICH and supports a complex role of monocytes in this disease. Larger studies will determine the extent to which these findings apply beyond the small cohort examined here.

Indexed as

BAF312intracerebral hemorrhagemonocytesiponimodstrokeTNF

Identifiers

PMID42501052
PMCPMC13401412

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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 OpenQuestion graph.