Evidence map›Paper›PMID 37957728›Full record

ArticleJournal of neuroinflammation2023

Spatial transcriptomics and neurofilament light chain reveal changes in lesion patterns in murine autoimmune neuroinflammation.

Tobias Brummer, Miriam Schillner, Falk Steffen, Flores Kneilmann, Beatrice Wasser, Timo Uphaus, Frauke Zipp, Stefan Bittner

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

6 citing papers in PubMed, 8 citations in OpenAlex.

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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

8 authors at 2 institutions in 1 country.

Tobias BrummerDepartment of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (Rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
Miriam SchillnerDepartment of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (Rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
Falk SteffenDepartment of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (Rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
Flores KneilmannDepartment of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (Rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
Beatrice WasserDepartment of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (Rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
Timo UphausDepartment of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (Rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
Frauke ZippDepartment of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (Rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
Stefan BittnerDepartment of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (Rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany. bittner@uni-mainz.de.
Johannes Gutenberg University Mainz · DEUniversity Medical Center of the Johannes Gutenberg University Mainz · DE

Funding

Deutsche Forschungsgemeinschaft CRC-TR-128
6 · The paper itself

Abstract

objectiveOngoing neuroaxonal damage is a major contributor to disease progression and long-term disability in multiple sclerosis. However, spatio-temporal distribution and pathophysiological mechanisms of neuroaxonal damage during acute relapses and later chronic disease stages remain poorly understood.

methodsHere, we applied immunohistochemistry, single-molecule array, spatial transcriptomics, and microglia/axon co-cultures to gain insight into spatio-temporal neuroaxonal damage in experimental autoimmune encephalomyelitis (EAE).

resultsAssociation of spinal cord white matter lesions and blood-based neurofilament light (sNfL) levels revealed a distinct, stage-dependent anatomical pattern of neuroaxonal damage: in chronic EAE, sNfL levels were predominately associated with anterolateral lumbar lesions, whereas in early EAE sNfL showed no correlation with lesions in any anatomical location. Furthermore, neuroaxonal damage in late EAE was largely confined to white matter lesions but showed a widespread distribution in early EAE. Following this pattern of neuroaxonal damage, spatial transcriptomics revealed a widespread cyto- and chemokine response at early disease stages, whereas late EAE was characterized by a prominent glial cell accumulation in white matter lesions. These findings were corroborated by immunohistochemistry and microglia/axon co-cultures, which further revealed a strong association between CNS myeloid cell activation and neuroaxonal damage both in vivo and in vitro.

interpretationOur findings indicate that CNS myeloid cells may play a crucial role in driving neuroaxonal damage in EAE. Moreover, neuroaxonal damage can progress in a stage-dependent centripetal manner, transitioning from normal-appearing white matter to focal white matter lesions. These insights may contribute to a better understanding of neurodegeneration and elevated sNfL levels observed in multiple sclerosis patients at different disease stages.

Indexed as

Encephalomyelitis, Autoimmune, ExperimentalMultiple SclerosisAnimalsHumansIntermediate FilamentsMiceNeuroinflammatory DiseasesTranscriptomeExperimental autoimmune encephalomyelitisMicrogliaMultiple sclerosisSerum neurofilamentSpatial transcriptomics

Identifiers

PMID37957728
PMCPMC10644497
OpenAlexW4388630388

What OpenQuestion holds

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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 OpenQuestion graph.