Evidence map›Paper›PMID 33645550›Full record

ArticleThe Journal of clinical investigation2021

Blood-brain barrier resealing in neuromyelitis optica occurs independently of astrocyte regeneration.

Anne Winkler, Claudia Wrzos, Michael Haberl, Marie-Theres Weil, Ming Gao, Wiebke Möbius, Francesca Odoardi, Dietmar R Thal, Mayland Chang, Ghislain Opdenakker and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

34 citing papers in PubMed, 51 citations in OpenAlex.

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  12. MOGJournal of neuroinflammation · 2025
    Review
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  19. CNS autoimmune response in the MAM/pilocarpine rat model of epileptogenic cortical malformation.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  20. 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

13 authors at 7 institutions in 4 countries.

Anne WinklerInstitute of Neuropathology and.
Claudia WrzosInstitute of Neuropathology and.
Michael HaberlInstitute for Multiple Sclerosis Research and Neuroimmunology, University Medical Center Göttingen, Göttingen, Germany.
Marie-Theres WeilElectron Microscopy Core Unit, Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany.
Ming GaoDepartment of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.
Wiebke MöbiusElectron Microscopy Core Unit, Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany.
Francesca OdoardiInstitute for Multiple Sclerosis Research and Neuroimmunology, University Medical Center Göttingen, Göttingen, Germany.
Dietmar R ThalDepartment of Imaging and Pathology, KU Leuven, and Department of Pathology, UZ Leuven, Leuven, Belgium.
Mayland ChangDepartment of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.
Ghislain OpdenakkerLaboratory of Immunobiology, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
Jeffrey L BennettDepartments of Neurology and Ophthalmology, Program in Neuroscience, University of Colorado at Anschutz Medical Campus, Aurora, Colorado, USA.
Stefan NesslerInstitute of Neuropathology and.
Christine StadelmannInstitute of Neuropathology and.
Institute of Neuroimmunology of the Slovak Academy of Sciences · SKNanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103 · DEUniversitätsmedizin Göttingen · DEUniversity of Notre Dame · USRega Institute for Medical Research · BEUniversität Ulm · DEUniversity of Colorado Anschutz Medical Campus · US

Funding

Humoral Immunity, Astrocyte Injury, and Demyelination in Neuromyelitis OpticaR01EY022936 · NEI · UNIVERSITY OF COLORADO DENVER · PI BENNETT, JEFFREY L · 2013 to 2022
$3.8M
NEI NIH HHS R01 EY022936
6 · The paper itself

Abstract

Approximately 80% of neuromyelitis optica spectrum disorder (NMOSD) patients harbor serum anti-aquaporin-4 autoantibodies targeting astrocytes in the CNS. Crucial for NMOSD lesion initiation is disruption of the blood-brain barrier (BBB), which allows the entrance of Abs and serum complement into the CNS and which is a target for new NMOSD therapies. Astrocytes have important functions in BBB maintenance; however, the influence of their loss and the role of immune cell infiltration on BBB permeability in NMOSD have not yet been investigated. Using an experimental model of targeted NMOSD lesions in rats, we demonstrate that astrocyte destruction coincides with a transient disruption of the BBB and a selective loss of occludin from tight junctions. It is noteworthy that BBB integrity is reestablished before astrocytes repopulate. Rather than persistent astrocyte loss, polymorphonuclear leukocytes (PMNs) are the main mediators of BBB disruption, and their depletion preserves BBB integrity and prevents astrocyte loss. Inhibition of PMN chemoattraction, activation, and proteolytic function reduces lesion size. In summary, our data support a crucial role for PMNs in BBB disruption and NMOSD lesion development, rendering their recruitment and activation promising therapeutic targets.

Indexed as

AnimalsAstrocytesBlood-Brain BarrierDisease Models, AnimalFemaleHumansLeukocytes, MononuclearNeuromyelitis OpticaRatsRats, Inbred LewDemyelinating disordersNeuroscienceNeutrophilsTight junctions

Identifiers

PMID33645550
PMCPMC7919716
OpenAlexW3135800658

What OpenQuestion holds

Textmetadata
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.