Evidence map›Paper›PMID 33931805›Full record

ArticleMolecular neurobiology2021

The Cytoskeletal Elements MAP2 and NF-L Show Substantial Alterations in Different Stroke Models While Elevated Serum Levels Highlight Especially MAP2 as a Sensitive Biomarker in Stroke Patients.

Bianca Mages, Thomas Fuhs, Susanne Aleithe, Alexandra Blietz, Constance Hobusch, Wolfgang Härtig, Stefan Schob, Martin Krueger, Dominik Michalski

Open access · hybridAbstract read
In one paragraph

Article in Molecular neurobiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 10% 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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

  1. Pooled it
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  6. BML-281 promotes neuronal differentiation by modulating Wnt/CaMolecular and cellular biochemistry · 2024
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  8. The role of serum/glucocorticoid-regulated kinase 1 in brain function following cerebral ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024
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  16. Neural cortical organoids from self-assembling human iPSC as a model to investigate neurotoxicity in brain ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023
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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

9 authors at 2 institutions in 1 country.

Bianca MagesInstitute of Anatomy, Leipzig University, Leipzig, Germany. bianca.mages@medizin.uni-leipzig.de.ORCID http://orcid.org/0000-0002-4761-2608
Thomas FuhsSection of Soft Matter Physics, Faculty of Physics and Geosciences, Leipzig University, Leipzig, Germany.
Susanne AleitheDepartment of Neurology, Leipzig University, Leipzig, Germany.
Alexandra BlietzDepartment of Neurology, Leipzig University, Leipzig, Germany.
Constance HobuschInstitute of Anatomy, Leipzig University, Leipzig, Germany.
Wolfgang HärtigPaul Flechsig Institute of Brain Research, Leipzig University, Leipzig, Germany.
Stefan SchobDepartment of Neuroradiology, Leipzig University, Leipzig, Germany.
Martin KruegerInstitute of Anatomy, Leipzig University, Leipzig, Germany.
Dominik MichalskiDepartment of Neurology, Leipzig University, Leipzig, Germany. dominik.michalski@medizin.uni-leipzig.de.
Leipzig University · DELeipzig University of Applied Sciences · DE

Funding

European Research Council Advanced Grant 741350European Social Funds (ESF) 100270131
6 · The paper itself

Abstract

In the setting of ischemic stroke, the neurofilament subunit NF-L and the microtubule-associated protein MAP2 have proven to be exceptionally ischemia-sensitive elements of the neuronal cytoskeleton. Since alterations of the cytoskeleton have been linked to the transition from reversible to irreversible tissue damage, the present study investigates underlying time- and region-specific alterations of NF-L and MAP2 in different animal models of focal cerebral ischemia. Although NF-L is increasingly established as a clinical stroke biomarker, MAP2 serum measurements after stroke are still lacking. Therefore, the present study further compares serum levels of MAP2 with NF-L in stroke patients. In the applied animal models, MAP2-related immunofluorescence intensities were decreased in ischemic areas, whereas the abundance of NF-L degradation products accounted for an increase of NF-L-related immunofluorescence intensity. Accordingly, Western blot analyses of ischemic areas revealed decreased protein levels of both MAP2 and NF-L. The cytoskeletal alterations are further reflected at an ultrastructural level as indicated by a significant reduction of detectable neurofilaments in cortical axons of ischemia-affected areas. Moreover, atomic force microscopy measurements confirmed altered mechanical properties as indicated by a decreased elastic strength in ischemia-affected tissue. In addition to the results from the animal models, stroke patients exhibited significantly elevated serum levels of MAP2, which increased with infarct size, whereas serum levels of NF-L did not differ significantly. Thus, MAP2 appears to be a more sensitive stroke biomarker than NF-L, especially for early neuronal damage. This perspective is strengthened by the results from the animal models, showing MAP2-related alterations at earlier time points compared to NF-L. The profound ischemia-induced alterations further qualify both cytoskeletal elements as promising targets for neuroprotective therapies.

Indexed as

Disease Models, AnimalAgedAged, 80 and overAnimalsBiomarkersBrain IschemiaFemaleHumansMaleMiceMice, Inbred C57BLMicrotubule-Associated ProteinsMiddle AgedNeurofilament ProteinsProspective StudiesRatsBiomarkersMAP2 protein, humanMicrotubule-Associated Proteinsneurofilament protein LNeurofilament ProteinsAtomic force microscopyBiomarkerCerebral ischemiaMAP2NF-LStroke

Identifiers

PMID33931805
PMCPMC8280005
OpenAlexW3159512995

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Registered trials

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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.