Evidence map›Paper›PMID 29718007›Full record

ArticlePediatric research2018

Upregulation of cholesterol 24-hydroxylase following hypoxia-ischemia in neonatal mouse brain.

Fuxin Lu, Jun Zhu, Selena Guo, Brandon J Wong, Farid F Chehab, Donna M Ferriero, Xiangning Jiang

Open access · bronzeAbstract read
In one paragraph

Article in Pediatric research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

16 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
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  9. Serum 24S-hydroxycholesterol predicts long-term brain structural and functional outcomes after hypoxia-ischemia in neonatal mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021
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  14. The key genes, phosphoproteins, processes, and pathways affected by efavirenz-activated CYP46A1 in the amyloid-decreasing paradigm of efavirenz treatment.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  15. CYP46A1 Activation by Efavirenz Leads to Behavioral Improvement without Significant Changes in Amyloid Plaque Load in the Brain of 5XFAD Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019
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  16. 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

7 authors at 3 institutions in 1 country.

Fuxin LuDepartment of Pediatrics, University of California San Francisco, San Francisco, California.
Jun ZhuDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, California.
Selena GuoDougherty Valley High School, San Ramon, California.
Brandon J WongUniversity of California Berkeley, Berkeley, California.
Farid F ChehabDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, California.
Donna M FerrieroDepartment of Pediatrics, University of California San Francisco, San Francisco, California.
Xiangning JiangDepartment of Pediatrics, University of California San Francisco, San Francisco, California.
University of California, San Francisco · USGreen Valley High School · USUniversity of California, Berkeley · US

Funding

Precision Therapy for Neonatal Brain InjuryR35NS097299 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIERO, DONNA M. · 2017 to 2024
$6.3M
Phospho-regulation of NMDA receptors in neonatal brain hypoxia-ischemiaR01NS084057 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JIANG, XIANGNING · 2014 to 2018
$1.7M
Regulation of brain cholesterol homeostasis following neonatal hypoxia-ischemiaR56NS114563 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JIANG, XIANGNING · 2020 to 2020
$520k
NINDS NIH HHS R01 NS084057NINDS NIH HHS R35 NS097299NINDS NIH HHS R56 NS114563
6 · The paper itself

Abstract

BackgroundMaintenance of cholesterol homeostasis is crucial for brain development. Brain cholesterol relies on de novo synthesis and is cleared primarily by conversion to 24S-hydroxycholesterol (24S-HC) with brain-specific cholesterol 24-hydroxylase (CYP46A1). We aimed to investigate the impact of hypoxia-ischemia (HI) on brain cholesterol metabolism in the neonatal mice.MethodsPostnatal day 9 C57BL/6 pups were subjected to HI using the Vannucci model. CYP46A1 expression was assessed with western blotting and its cellular localization was determined using immunofluorescence staining. The amount of brain cholesterol, 24S-HC in the cortex and in the serum, was measured with enzyme-linked immunosorbent assay (ELISA).ResultsThere was a transient cholesterol loss at 6 h after HI. CYP46A1 was significantly upregulated at 6 and 24 h following HI with a concomitant increase of 24S-HC in the ipsilateral cortex and in the serum. The serum levels of 24S-HC correlated with those in the brain, as well as with necrotic and apoptotic cell death evaluated by the expression of spectrin breakdown products and cleaved caspase-3 at 6 and 24 h after HI.ConclusionEnhanced cholesterol turnover by activation of CYP46A1 represents disrupted brain cholesterol homeostasis early after neonatal HI. 24S-HC might be a novel blood biomarker for severity of hypoxic-ischemic encephalopathy with potential clinical application.

Indexed as

Gene Expression Regulation, EnzymologicAnimalsAnimals, NewbornBiomarkersBrainCerebral CortexCholesterolCholesterol 24-HydroxylaseEnzyme-Linked Immunosorbent AssayHydroxycholesterolsHypoxiaHypoxia-Ischemia, BrainMiceMice, Inbred C57BLNeuronsOligodendroglia24-hydroxycholesterolBiomarkersCholesterolCholesterol 24-HydroxylaseHydroxycholesterols

Identifiers

PMID29718007
PMCPMC6019156
OpenAlexW2800893383

What OpenQuestion holds

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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 OpenQuestion graph.