Evidence map›Paper›PMID 40964705›Full record

ArticleStroke2025

Experimental Ischemic Stroke-Induced Alpha-Synuclein Pathology Enhances Endothelial Inflammatory Response and Impairs Angiogenesis.

Tizibt Ashine Bogale, Domenico Mercurio, Alessia Valente, Serena Seminara, Gaia Faustini, Francesca Longhena, Aurora Bianchi, Stefania Mitola, Arianna Bellucci, Stefano Fumagalli and 1 more

Abstract read
In one paragraph

Article in Stroke, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. 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

11 authors.

Tizibt Ashine BogaleDivision of Pharmacology (T.A.B., G.F., F.L., S.M., A. Bellucci, M.P.), Department of Molecular and Translational Medicine, University of Brescia, Italy.ORCID 0000-0002-0905-2654
Domenico MercurioDepartment of Acute Brain and Cardiovascular Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy (T.A.B., D.M., A.V., S.S., A. Bianchi, S.F.).ORCID 0000-0001-5101-7222
Alessia ValenteDepartment of Acute Brain and Cardiovascular Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy (T.A.B., D.M., A.V., S.S., A. Bianchi, S.F.).ORCID 0000-0002-6917-9278
Serena SeminaraDepartment of Acute Brain and Cardiovascular Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy (T.A.B., D.M., A.V., S.S., A. Bianchi, S.F.).
Gaia FaustiniDivision of Pharmacology (T.A.B., G.F., F.L., S.M., A. Bellucci, M.P.), Department of Molecular and Translational Medicine, University of Brescia, Italy.ORCID 0000-0002-0751-3082
Francesca LonghenaDivision of Pharmacology (T.A.B., G.F., F.L., S.M., A. Bellucci, M.P.), Department of Molecular and Translational Medicine, University of Brescia, Italy.
Aurora BianchiDepartment of Acute Brain and Cardiovascular Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy (T.A.B., D.M., A.V., S.S., A. Bianchi, S.F.).
Stefania MitolaDivision of Pharmacology (T.A.B., G.F., F.L., S.M., A. Bellucci, M.P.), Department of Molecular and Translational Medicine, University of Brescia, Italy.ORCID 0000-0002-5557-738X
Arianna BellucciDivision of Pharmacology (T.A.B., G.F., F.L., S.M., A. Bellucci, M.P.), Department of Molecular and Translational Medicine, University of Brescia, Italy.ORCID 0000-0002-9581-1919
Stefano FumagalliDepartment of Acute Brain and Cardiovascular Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy (T.A.B., D.M., A.V., S.S., A. Bianchi, S.F.).ORCID 0000-0003-3598-6263
Marina PizziDivision of Pharmacology (T.A.B., G.F., F.L., S.M., A. Bellucci, M.P.), Department of Molecular and Translational Medicine, University of Brescia, Italy.ORCID 0000-0002-4857-5204

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundα-Syn (alpha-synuclein) increases and oligomerization contributes to ischemic brain damage. Nevertheless, the exact mechanisms of ischemia-induced α-Syn pathology after stroke are understudied. In this exploratory and hypothesis-testing study, we specifically investigated how ischemia-induced α-Syn pathology impacts vascular inflammation and angiogenesis.

methodsTransient focal cerebral ischemia was induced in C57BL/6J wild-type and C57BL/6S mice with spontaneous deletion of α-Syn. In total, 72 mice were randomized to receive sham (12) or ischemia (60), with 1:1 allocation to genotype. Ischemic mice were included if presenting ≥3 intraischemic focal deficits. Experimental end points were 48 hours (acute phase) and 7 days (subacute phase) of reperfusion. Sensorimotor assessment, elevated plus maze, and survival analysis were stroke outcome readouts. Brain samples were collected for quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry. In vitro ischemia in brain microvascular endothelial cells was used to investigate the direct effect of extracellular α-Syn.

resultsIn vivo, cerebral ischemia induced α-Syn 2.5-fold change gene expression, 2.7- to 3.2-fold-change protein oligomerization with apparent localization around cortical ischemic vessels. Improved subacute functional recovery linked to better survival was observed in C57BL/6S α-Syn null (87% to end point) versus C57BL/6J (45%) ischemic mice. The α-Syn null mice had reduced expression of

conclusionsThese findings indicate that ischemia-triggered pathological α-Syn leads to worse outcome in stroke mice by promoting endothelial inflammatory response and immune cell infiltration during the acute phase and by limiting angiogenesis in the subacute phase.

Indexed as

alpha-SynucleinBrain IschemiaEndothelial CellsIschemic StrokeNeovascularization, PathologicAngiogenesisAnimalsDisease Models, AnimalInflammationMaleMiceMice, Inbred C57BLMice, Knockoutalpha-Synucleinalpha-synucleinangiogenesisinflammationischemiastroke

Identifiers

PMID40964705
PMCPMC12643574

What Socratic holds

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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 Socratic graph.