ReviewThe Journal of physiology2018
A working model for hypothermic neuroprotection.
Review in The Journal of physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Treating the symptom or treating the disease in neonatal seizures: a systematic review of the literature.Italian journal of pediatrics · 2021Pooled it
- Advancements in Neonatal Brain Injury Treatment: Nanomedicine-Based Strategies.International journal of nanomedicine · 2026Review
- Lipidomic Comparison of Detergent-Soluble and Detergent-Resistant Lipid Domains Isolated From Rat Cerebellum and the Effect of Hypoxia-Ischemia Using UPLC-HDMSJournal of mass spectrometry : JMS · 2026Article
- The Potential Clinical Relevance of Necrosis-Necroptosis Pathways for Hypoxic-Ischaemic Encephalopathy.Cells · 2025Review
- Peritoneal delivery of capsinoids, nonpungent TRPV1 agonists, induces mild hypothermia in conscious mice through TRPV1 activation of visceral vagal afferents.Scientific reports · 2025Article
- Preconditioning and Posttreatment Strategies in Neonatal Hypoxic-Ischemic Encephalopathy: Recent Advances and Clinical Challenges.Molecular neurobiology · 2025Review
- Slow rewarming after hypothermia does not ameliorate white matter injury after hypoxia-ischemia in near-term fetal sheep.Pediatric research · 2025Article
- Dimethyl Fumarate Strongly Ameliorates Gray and White Matter Brain Injury and Modulates Glial Activation after Severe Hypoxia-Ischemia in Neonatal Rats.Antioxidants (Basel, Switzerland) · 2024Article
- Neuroprotective therapies in the NICU in preterm infants: present and future (Neonatal Neurocritical Care Series).Pediatric research · 2024Review
- Hypothermia Treatment after Hypoxia-Ischemia in Glutathione Peroxidase-1 Overexpressing Mice.Developmental neuroscience · 2024Article
- Advances in neonatal cell therapies: Proceedings of the First Neonatal Cell Therapies Symposium (2022).Pediatric research · 2023Review
- A narrative review on treatment strategies for neonatal hypoxic ischemic encephalopathy.Translational pediatrics · 2023Review
- Hypothermia increases cold-inducible protein expression and improves cerebellar-dependent learning after hypoxia ischemia in the neonatal rat.Pediatric research · 2023Article
- Temperature dysregulation during therapeutic hypothermia predicts long-term outcome in neonates with HIE.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Neuroprotective therapies in the NICU in term infants: present and future.Pediatric research · 2023Review
- Therapeutic Hypothermia Attenuates Cortical Interneuron Loss after Cerebral Ischemia in Near-Term Fetal Sheep.International journal of molecular sciences · 2023Article
- Choline Improves Neonatal Hypoxia-Ischemia Induced Changes in Male but Not Female Rats.International journal of molecular sciences · 2022Article
- Neonatal hypoxia ischemia redistributes L1 cell adhesion molecule into rat cerebellar lipid rafts.Pediatric research · 2022Article
- Selective Cerebrospinal Fluid Hypothermia: Bioengineering Development and In Vivo Study of an Intraventricular Cooling Device (V-COOL).Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Targeting Persistent Neuroinflammation after Hypoxic-Ischemic Encephalopathy-Is Exendin-4 the Answer?International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Therapeutic hypothermia significantly improves survival without disability in near-term and full-term newborns with moderate to severe hypoxic-ischaemic encephalopathy. However, hypothermic neuroprotection is incomplete. The challenge now is to find ways to further improve outcomes. One major limitation to progress is that the specific mechanisms of hypothermia are only partly understood. Evidence supports the concept that therapeutic cooling suppresses multiple extracellular death signals, including intracellular pathways of apoptotic and necrotic cell death and inappropriate microglial activation. Thus, the optimal depth of induced hypothermia is that which effectively suppresses the cell death pathways after hypoxia-ischaemia, but without inhibiting recovery of the cellular environment. Thus mild hypothermia needs to be continued until the cell environment has recovered until it can actively support cell survival. This review highlights that key survival cues likely include the inter-related restoration of neuronal activity and growth factor release. This working model suggests that interventions that target overlapping mechanisms, such as anticonvulsants, are unlikely to materially augment hypothermic neuroprotection. We suggest that further improvements are most likely to be achieved with late interventions that maximise restoration of the normal cell environment after therapeutic hypothermia, such as recombinant human erythropoietin or stem cell therapy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.