Evidence map›Paper›PMID 35690757›Full record

ArticleJournal of neuroinflammation2022

Persistent cortical and white matter inflammation after therapeutic hypothermia for ischemia in near-term fetal sheep.

Kelly Q Zhou, Laura Bennet, Guido Wassink, Alice McDouall, Maurice A Curtis, Blake Highet, Taylor J Stevenson, Alistair J Gunn, Joanne O Davidson

Open access · goldAbstract readRandomized Controlled Trial, Veterinary
In one paragraph

Article in Journal of neuroinflammation, 2022. 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
8.4field-weighted citation impact, top 2% 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. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Stay cool and keep moving forwards.Pediatric research · 2025
    Article
  9. Dysmaturation of sleep state and electroencephalographic activity after hypoxia-ischaemia in preterm fetal sheep.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Brain organoids for hypoxic-ischemic studies: from bench to bedside.Cellular and molecular life sciences : CMLS · 2023
    Review
  15. Article
  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

9 authors at 1 institution in 1 country.

Kelly Q ZhouDepartment of Physiology, School of Medical Sciences, The University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
Laura BennetDepartment of Physiology, School of Medical Sciences, The University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
Guido WassinkDepartment of Physiology, School of Medical Sciences, The University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
Alice McDouallDepartment of Physiology, School of Medical Sciences, The University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
Maurice A CurtisDepartment of Anatomy and Medical Imaging, School of Medical Sciences, The University of Auckland, Auckland, New Zealand.
Blake HighetDepartment of Anatomy and Medical Imaging, School of Medical Sciences, The University of Auckland, Auckland, New Zealand.
Taylor J StevensonDepartment of Pharmacology, School of Medical Sciences, The University of Auckland, Auckland, New Zealand.
Alistair J GunnDepartment of Physiology, School of Medical Sciences, The University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
Joanne O DavidsonDepartment of Physiology, School of Medical Sciences, The University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand. joanne.davidson@auckland.ac.nz.
University of Auckland · NZ

Funding

Health Research Council of New Zealand 16/003Health Research Council of New Zealand 17/601Marsden Fund 17-UOA232
6 · The paper itself

Abstract

backgroundTherapeutic hypothermia significantly improves outcomes after moderate-severe hypoxic-ischemic encephalopathy (HIE), but it is partially effective. Although hypothermia is consistently associated with reduced microgliosis, it is still unclear whether it normalizes microglial morphology and phenotype.

methodsNear-term fetal sheep (n = 24) were randomized to sham control, ischemia-normothermia, or ischemia-hypothermia. Brain sections were immunohistochemically labeled to assess neurons, microglia and their interactions with neurons, astrocytes, myelination, and gitter cells (microglia with cytoplasmic lipid granules) 7 days after cerebral ischemia. Lesions were defined as areas with complete loss of cells. RNAscope

resultsIschemia-normothermia was associated with severe loss of neurons and myelin (p < 0.05), with extensive lesions, astrogliosis and microgliosis with a high proportion of gitter cells (p < 0.05). Microglial wrapping of neurons was present in both the ischemia groups. Hypothermia improved neuronal survival, suppressed lesions, gitter cells and gliosis (p < 0.05), and attenuated the reduction of myelin area fraction. The "M1" marker CD86 and "M2" marker CD206 were upregulated after ischemia. Hypothermia partially suppressed CD86 in the cortex only (p < 0.05), but did not affect CD206.

conclusionsHypothermia prevented lesions after cerebral ischemia, but only partially suppressed microglial wrapping and M1 marker expression. These data support the hypothesis that persistent upregulation of injurious microglial activity may contribute to partial neuroprotection after hypothermia, and that immunomodulation after rewarming may be an important therapeutic target.

Indexed as

HypothermiaHypothermia, InducedHypoxia-Ischemia, BrainWhite MatterAnimalsGliosisInflammationIschemiaSheepElectroencephalogramGitter cellsHypoxia-ischemiaMicroglial phenotypeNeuroinflammationTherapeutic hypothermia

Identifiers

PMID35690757
PMCPMC9188214
OpenAlexW4282945055

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.