Evidence map›Paper›PMID 30975982›Full record

ArticleCell death & disease2019

Minocycline mitigates the effect of neonatal hypoxic insult on human brain organoids.

Erin M Boisvert, Robert E Means, Michael Michaud, Joseph A Madri, Samuel G Katz

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
7.7field-weighted citation impact, top 3% 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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Advances in three-dimensional modeling of ischemic injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. A Comprehensive Review on Utilizing Human Brain Organoids to Study Neuroinflammation in Neurological Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
    Review
  12. "ArmedFrontiers in cell and developmental biology · 2025
    Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Brain organoids for hypoxic-ischemic studies: from bench to bedside.Cellular and molecular life sciences : CMLS · 2023
    Review
  18. Review
  19. 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
    Article
  20. 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 at 1 institution in 1 country.

Erin M BoisvertDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Robert E MeansDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Michael MichaudDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Joseph A MadriDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Samuel G KatzDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA. Samuel.Katz@yale.edu.
Yale University · US

Funding

Yale Cancer Biology Training GrantT32CA193200 · NCI · YALE UNIVERSITY · PI PETER M GLAZER, Qin Yan · 2016 to 2026
$3.6M
Cell Death Regulation by Pro-Apoptotic BOK in CardiomyocytesR01HL131793 · NHLBI · YALE UNIVERSITY · PI KATZ, SAMUEL G · 2016 to 2020
$2.3M
NCI NIH HHS T32 CA193200NHLBI NIH HHS R01 HL131793
6 · The paper itself

Abstract

Neonatal hypoxic injury (NHI) is a devastating cause of disease that affects >60% of babies born with a very low birth weight, resulting in significant morbidity and mortality, including life-long neurological consequences such as seizures, cerebral palsy, and intellectual disability. Hypoxic injury results in increased neuronal death, which disrupts normal brain development. Although animal model systems have been useful to study the effects of NHI, they do not fully represent the uniqueness and complexities of the human brain. To better understand the effects of hypoxia on human brain development, we have generated a brain organoid protocol and evaluated these cells over the course of 6 months. As anticipated, the expression of a forebrain marker, FOXG1, increased and then remained expressed over time, while there was a transition in the expression of the deep-layer (TBR1) and upper-layer (SATB2) cortical markers. In addition, ventral genes (Eng1 and Nkx2.1) as well as markers of specialized nonneuronal cells (Olig2 and GFAP) also increased at later time points. We next tested the development of our in vitro cerebral organoid model at different oxygen concentrations and found that hypoxia repressed gene markers for forebrain, oligodendrocytes, glial cells, and cortical layers, as well as genes important for the migration of cortical neurons. In contrast, ventral markers were either unaffected or even increased in expression with hypoxic insult. Interestingly, the negative effect of hypoxia on the dorsal brain genes as well as oligodendrocytes, and neuronal progenitors could be mitigated by the use of minocycline, an FDA-approved small molecule. Taken together, we have generated a unique and relevant in vitro human brain model system to study diseases such as NHI as well as their potential treatments. Using this system, we have shown the efficacy of minocycline for human NHI.

Indexed as

BrainCell DeathHuman Embryonic Stem CellsHumansHypoxia, BrainHypoxia-Ischemia, BrainMinocyclineNeuronsOrganoidsProto-Oncogene Proteins c-bcl-2SOXB1 Transcription FactorsTime FactorsMinocyclineProto-Oncogene Proteins c-bcl-2SOX2 protein, humanSOXB1 Transcription Factors

Identifiers

PMID30975982
PMCPMC6459920
OpenAlexW2938338045

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.