Evidence mapPaperPMID 39224978Full record

ArticleStroke2024

Role of Cholesterol Metabolic Enzyme CYP46A1 and Its Metabolite 24S-Hydroxycholesterol in Ischemic Stroke.

Huawei Sun, Tao Yang, Roger P Simon, Zhi-Gang Xiong, Tiandong Leng

Abstract read
In one paragraph

Article in Stroke, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. 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

5 authors.

Huawei SunDepartment of Neurobiology, Morehouse School of Medicine, Atlanta, GA.
Tao YangDepartment of Neurobiology, Morehouse School of Medicine, Atlanta, GA.
Roger P SimonDepartment of Neurobiology, Morehouse School of Medicine, Atlanta, GA.
Zhi-Gang XiongDepartment of Neurobiology, Morehouse School of Medicine, Atlanta, GA.ORCID 0000-0002-2824-4168
Tiandong LengDepartment of Neurobiology, Morehouse School of Medicine, Atlanta, GA.ORCID 0000-0003-2072-4340

Funding

The role of cholesterol metabolic enzyme CYP46A1 and its metabolite 24S-hydroxycholesterol in ischemic stroke.R01NS128018 · MOREHOUSE SCHOOL OF MEDICINE · 2025 to 2025
$355k
Mechanisms of ASIC-mediated neuronal injuryR01NS104349 · NINDS · MOREHOUSE SCHOOL OF MEDICINE · PI ROGER Pancoast SIMON · 2021 to 2021
$313k
NIGMS NIH HHS SC3 GM122593NINDS NIH HHS R01 NS104349NINDS NIH HHS R01 NS128018
6 · The paper itself

Abstract

backgroundFor several decades, it has been recognized that overactivation of the glutamate-gated N-methyl-D-aspartate receptors (NMDARs) and subsequent Ca

methodsWe tested this hypothesis using electrophysiological, pharmacological, and transgenic approaches and in vitro and in vivo cerebral ischemia models.

resultsOur data show that 24S-HC potentiates NMDAR activation in primary cultured mouse cortical neurons in a concentration-dependent manner. At 10 µmol/L, it dramatically increases the steady-state currents by 51% and slightly increases the peak currents by 20%. Furthermore, 24S-HC increases NMDA and oxygen-glucose deprivation-induced cortical neuronal injury. The increased neuronal injury is largely abolished by NMDAR channel blocker MK-801, suggesting an NMDAR-dependent mechanism. Pharmacological inhibition of CYP46A1 by voriconazole or gene knockout of

conclusionsThese results identify a new mechanism and signaling cascade that critically impacts stroke outcome: CYP46A1 → 24S-HC → NMDAR → ischemic brain injury. They offer proof of principle for further development of new strategies for stroke intervention by targeting CYP46A1 or its metabolite 24S-HC.

Indexed as

Cholesterol 24-HydroxylaseHydroxycholesterolsIschemic StrokeReceptors, N-Methyl-D-AspartateAnimalsBrain IschemiaCells, CulturedCholesterolMaleMiceMice, Inbred C57BLMice, KnockoutNeurons24-hydroxycholesterolCholesterolCholesterol 24-HydroxylaseHydroxycholesterolsReceptors, N-Methyl-D-Aspartate24-hydroxycholesterolbrain ischemiacholesterolcholesterol 24-hydroxylasestroke

Identifiers

PMID39224978
PMCPMC11421972

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.