Evidence map›Paper›PMID 26739327›Full record

ArticleNeuroscience2016

White matter apoptosis is increased by delayed hypothermia and rewarming in a neonatal piglet model of hypoxic ischemic encephalopathy.

B Wang, J S Armstrong, M Reyes, E Kulikowicz, J-H Lee, D Spicer, U Bhalala, Z-J Yang, R C Koehler, L J Martin and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 2 pooled it
13.8field-weighted citation impact, top 1% 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

37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.

  1. Pooled it
  2. RECOVER Guidelines: Newborn Resuscitation in Dogs and Cats. Clinical Guidelines.Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001) · 2025
    Guideline
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  19. Limited benefit of slow rewarming after cerebral hypothermia for global cerebral ischemia in near-term fetal sheep.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019
    Article
  20. 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

11 authors at 1 institution in 1 country.

B WangDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD (JHU), United States.
J S ArmstrongDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD (JHU), United States.
M ReyesDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD (JHU), United States.
E KulikowiczDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD (JHU), United States.
J-H LeeDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD (JHU), United States.
D SpicerDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD (JHU), United States.
U BhalalaDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD (JHU), United States.
Z-J YangDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD (JHU), United States.
R C KoehlerDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD (JHU), United States.
L J MartinDepartment of Pathology, Division of Neuropathology, JHU, United States.
J K LeeDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD (JHU), United States. Electronic address: jklee@jhmi.edu.
Johns Hopkins University · US

Funding

Therapeutic Strategies for Neonatal Hypoxic-Ischemiic EncephalopathyR01NS060703 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KOEHLER, RAYMOND CHARLES · 2008 to 2019
$3.9M
Neuronal injury after pediatric cardiac arrest, hypothermia, and rewarmingK08NS080984 · NINDS · JOHNS HOPKINS UNIVERSITY · PI LEE, JENNIFER KIM · 2014 to 2018
$960k
End-tidal carbon dioxide (ETCO2) directed cardiopulmonary resuscitation (CPR)R21HD072845 · NICHD · JOHNS HOPKINS UNIVERSITY · PI SHAFFNER, DONALD H · 2014 to 2015
$440k
NICHD NIH HHS R21 HD072845NICHD NIH HHS R21HD072845NINDS NIH HHS K08 NS080984NINDS NIH HHS K08 NS080984-01NINDS NIH HHS L40 NS066505NINDS NIH HHS R01 NS060703
6 · The paper itself

Abstract

Therapeutic hypothermia is widely used to treat neonatal hypoxic ischemic (HI) brain injuries. However, potentially deleterious effects of delaying the induction of hypothermia and of rewarming on white matter injury remain unclear. We used a piglet model of HI to assess the effects of delayed hypothermia and rewarming on white matter apoptosis. Piglets underwent HI injury or sham surgery followed by normothermic or hypothermic recovery at 2h. Hypothermic groups were divided into those with no rewarming, slow rewarming at 0.5°C/h, or rapid rewarming at 4°C/h. Apoptotic cells in the subcortical white matter of the motor gyrus, corpus callosum, lateral olfactory tract, and internal capsule at 29h were identified morphologically and counted by hematoxylin & eosin staining. Cell death was verified by terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) assay. White matter neurons were also counted, and apoptotic cells were immunophenotyped with the oligodendrocyte marker 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase). Hypothermia, slow rewarming, and rapid rewarming increased apoptosis in the subcortical white matter relative to normothermia (p<0.05). The number of white matter neurons was not lower in groups with more apoptosis after hypothermia or rapid rewarming, indicating that the apoptosis occurred among glial cells. Hypothermic piglets had more apoptosis in the lateral olfactory tract than those that were rewarmed (p<0.05). The promotion of apoptosis by hypothermia and rewarming in these regions was independent of HI. In the corpus callosum, HI piglets had more apoptosis than shams after normothermia, slow rewarming, and rapid rewarming (p<0.05). Many apoptotic cells were myelinating oligodendrocytes identified by CNPase positivity. Our results indicate that delaying the induction of hypothermia and rewarming are associated with white matter apoptosis in a piglet model of HI; in some regions these temperature effects are independent of HI. Vulnerable cells include myelinating oligodendrocytes. This study identifies a deleterious effect of therapeutic hypothermia in the developing brain.

Indexed as

Hypothermia, InducedRewarmingAnimalsAnimals, NewbornApoptosisBlood PressureCaspase 3Disease Models, AnimalDopamineHypoxia-Ischemia, BrainIn Situ Nick-End LabelingMalePhenylephrineStatistics, NonparametricSwineTime FactorsCaspase 3DopaminePhenylephrineasphyxiaheart arresthypothermianewbornrewarmingwhite matter

Identifiers

PMID26739327
PMCPMC4724504
OpenAlexW2209423325

What OpenQuestion 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 OpenQuestion graph.