ArticleScientific reports2020
Variability and sex-dependence of hypothermic neuroprotection in a rat model of neonatal hypoxic-ischaemic brain injury: a single laboratory meta-analysis.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 47 citations in OpenAlex.
- Evaluation of heterogeneity in effect of therapeutic hypothermia by sex among infants with neonatal encephalopathy.Pediatric research · 2023Trial
- Pharmacokinetics and Brain Distribution of a Purine-Derived Neuroprotective Agent after Intranasal Administration in Neonatal Rats with Hypoxic-Ischemic Brain Injury.Pharmaceutical research · 2026Article
- Optimizing therapeutic hypothermia conditions in a translational preclinical model of neonatal hypoxia-ischemia in rats.Pediatric research · 2026Article
- Comparing neuroprotective drug efficacy in rodent neonatal brain injury models.Pediatric research · 2026Article
- Targeting the mitochondrial thermogenesis pathway for neuroprotection in neonatal hypoxic-ischemic encephalopathy by curcumin.Acta pharmacologica Sinica · 2026Article
- Article
- Neonatal Hypoxic-Ischemic Encephalopathy: From the Limitations of Therapeutic Hypothermia to Precision Intervention.Drug design, development and therapy · 2026Review
- Sex-Dependent Long-Term Neurobehavioral Recovery in Experimental Neonatal Hypoxic-Ischemic Encephalopathy.Pharmacology research & perspectives · 2025Article
- Comparing Neuroprotective Drug Efficacy in Rodent Neonatal Brain Injury Models.bioRxiv : the preprint server for biology · 2025Article
- Sex dimorphism in brain cell death after hypoxia-ischemia in newborn piglets.Pediatric research · 2025Article
- What are the implications of sex differences in cell death for treatment after neonatal hypoxia-ischemia, if any?Pediatric research · 2025Article
- Pretreatment with oleuropein protects the neonatal brain from hypoxia-ischemia by inhibiting apoptosis and neuroinflammation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025Article
- The Neuroprotective Effects of Caffeine in a Neonatal Hypoxia-Ischemia Model are Regulated through the AMPK/mTOR Pathway.International journal of biological sciences · 2025Article
- Protective Effects of Early Neonatal Methylxanthine Treatment on Cognitive and Language Outcomes in Premature Infants with and without High-Risk Perinatal Factors.Developmental neuroscience · 2025Article
- Antenatal Magnesium Sulfate Benefits Female Preterm Infants but Results in Poor Male Outcomes.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Pharmacokinetics of 7,8-dihydroxyflavone in neonatal mice with hypoxia-ischemia related brain injury.Frontiers in pharmacology · 2024Article
- Impact of sex, race, and social determinants of health on neonatal outcomes.Frontiers in pediatrics · 2024Review
- Hypothermia combined with extracellular vesicles from clonally expanded immortalized mesenchymal stromal cells improves neurodevelopmental impairment in neonatal hypoxic-ischemic brain injury.Journal of neuroinflammation · 2023Article
- Does sex materially modulate responses to therapeutic hypothermia?Pediatric research · 2023Article
- Sex Vulnerabilities to Hypoxia-Ischemia at Birth.JAMA network open · 2023Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapeutic hypothermia (HT) is standard care for term infants with hypoxic-ischaemic (HI) encephalopathy. However, the efficacy of HT in preclinical models, such as the Vannucci model of unilateral HI in the newborn rat, is often greater than that reported from clinical trials. Here, we report a meta-analysis of data from every experiment in a single laboratory, including pilot data, examining the effect of HT in the Vannucci model. Across 21 experiments using 106 litters, median (95% CI) hemispheric area loss was 50.1% (46.0-51.9%; n = 305) in the normothermia group, and 41.3% (35.1-44.9%; n = 317) in the HT group, with a bimodal injury distribution. Median neuroprotection by HT was 17.6% (6.8-28.3%), including in severe injury, but was highly-variable across experiments. Neuroprotection was significant in females (p < 0.001), with a non-significant benefit in males (p = 0.07). Animals representing the median injury in each group within each litter (n = 277, 44.5%) were also analysed using formal neuropathology, which showed neuroprotection by HT throughout the brain, particularly in females. Our results suggest an inherent variability and sex-dependence of the neuroprotective response to HT, with the majority of studies in the Vannucci model vastly underpowered to detect true treatment effects due to the distribution of injury.
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