Evidence map›Paper›PMID 37058487›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

Molecular profiling of the stroke-induced alterations in the cerebral microvasculature reveals promising therapeutic candidates.

Keri Callegari, Sabyasachi Dash, Hiroki Uchida, Yuto Shingai, Catherine Liu, Anne Khodarkovskaya, Yunkyoung Lee, Akira Ito, Amanda Lopez, Tuo Zhang and 3 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

14 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
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  4. Predictor Role ofMedicina (Kaunas, Lithuania) · 2025
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  13. Targeting lipid nanoparticles to the blood-brain barrier to ameliorate acute ischemic stroke.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  14. Article
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 1 institution in 1 country.

Keri CallegariDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065.
Sabyasachi DashDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065.
Hiroki UchidaDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065.
Yuto ShingaiDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065.
Catherine LiuDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065.
Anne KhodarkovskayaDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065.ORCID 0000-0001-5608-335X
Yunkyoung LeeDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065.
Akira ItoDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065.
Amanda LopezDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065.
Tuo ZhangGenomics Resources Core Facility, Weill Cornell Medicine, New York, NY 10065.ORCID 0000-0001-5396-918X
Jenny XiangGenomics Resources Core Facility, Weill Cornell Medicine, New York, NY 10065.ORCID 0000-0003-0484-2769
Michael J KlukDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065.
Teresa SanchezDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065.
Cornell University · US

Funding

Endothelial Sphingolipid Signaling in Post-Sepsis Cognitive Impairment.R01NS114561 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI SANCHEZ GARCIA-VAO, TERESA · 2020 to 2024
$2.4M
Sphingolipid Signaling in Endothelial Responses to InjuryR01HL094465 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI SANCHEZ GARCIA-VAO, TERESA · 2009 to 2013
$2.1M
NHLBI NIH HHS R01 HL094465NINDS NIH HHS R01 NS114561
6 · The paper itself

Abstract

Stroke-induced cerebral microvascular dysfunction contributes to aggravation of neuronal injury and compromises the efficacy of current reperfusion therapies. Understanding the molecular alterations in cerebral microvessels in stroke will provide original opportunities for scientific investigation of novel therapeutic strategies. Toward this goal, using a recently optimized method which minimizes cell activation and preserves endothelial cell interactions and RNA integrity, we conducted a genome-wide transcriptomic analysis of cerebral microvessels in a mouse model of stroke and compared these transcriptomic alterations with the ones observed in human, nonfatal, brain stroke lesions. Results from these unbiased comparative analyses have revealed the common alterations in mouse stroke microvessels and human stroke lesions and identified shared molecular features associated with vascular disease (e.g., Serpine1/Plasminogen Activator Inhibitor-1, Hemoxygenase-1), endothelial activation (e.g., Angiopoietin-2), and alterations in sphingolipid metabolism and signaling (e.g., Sphigosine-1-Phosphate Receptor 2). Sphingolipid profiling of mouse cerebral microvessels validated the transcript data and revealed the enrichment of sphingomyelin and sphingoid species in the cerebral microvasculature compared to brain and the stroke-induced increase in ceramide species. In summary, our study has identified novel molecular alterations in several microvessel-enriched, translationally relevant, and druggable targets, which are potent modulators of endothelial function. Our comparative analyses have revealed the presence of molecular features associated with cerebral microvascular dysfunction in human chronic stroke lesions. The results shared here provide a detailed resource for therapeutic discovery of candidates for neurovascular protection in stroke and potentially, other pathologies exhibiting cerebral microvascular dysfunction.

Indexed as

StrokeAnimalsBlood-Brain BarrierBrainEndotheliumHumansMiceMicrovesselsSphingolipidsSphingolipidsblood brain barriercardiovascular diseasescerebrovascular diseasessphingolipidsvascular biology

Identifiers

PMID37058487
PMCPMC10120001
OpenAlexW4365483412

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.