ArticleJournal of neuroinflammation2018
Effect of hypothermia on interleukin-1 receptor antagonist pharmacodynamics in inflammatory-sensitized hypoxic-ischemic encephalopathy of term newborns.
Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04816331 (Follow-up of Inflammatory Responses and Multiorgan Outcomes FoLlowing Neonatal Brain injurY), which is not on this map. Cited by 8 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Follow-up of Inflammatory Responses and Multiorgan Outcomes FoLlowing Neonatal Brain injurY
Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Neurological Outcome Following Newborn Encephalopathy With and Without Perinatal Infection: A Systematic Review.Frontiers in pediatrics · 2021Pooled it
- Interleukin-1: an important target for perinatal neuroprotection?Neural regeneration research · 2023Review
- No neuroprotective effect of therapeutic hypothermia following lipopolysaccharide-sensitized hypoxia-ischemia: a newborn piglet study.Frontiers in pediatrics · 2023Article
- Preventing Brain Damage from Hypoxic-Ischemic Encephalopathy in Neonates: Update on Mesenchymal Stromal Cells and Umbilical Cord Blood Cells.American journal of perinatology · 2022Review
- Necroptosis Blockade Potentiates the Neuroprotective Effect of Hypothermia in Neonatal Hypoxic-Ischemic Encephalopathy.Biomedicines · 2022Article
- A Single Administration of Riluzole Applied Acutely After Spinal Cord Injury Attenuates Pro-inflammatory Activity and Improves Long-Term Functional Recovery in Rats.Journal of molecular neuroscience : MN · 2022Article
- NAC and Vitamin D Restore CNS Glutathione in Endotoxin-Sensitized Neonatal Hypoxic-Ischemic Rats.Antioxidants (Basel, Switzerland) · 2021Article
- The overexpression of RBM3 alleviates TBI-induced behaviour impairment and AD-like tauopathy in mice.Journal of cellular and molecular medicine · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHypothermia is increasingly tested in several neurological conditions, such as neonatal encephalopathy, stroke, traumatic brain injury, subarachnoid hemorrhage, spinal cord injury, and neurological outcomes of cardiac arrest. Current studies aim to increase benefits of hypothermia with new add-on therapies including immunomodulatory agents. Hypothermia has been shown to affect the metabolism of commonly used drugs, including those acting on neuroimmune pathways.
objectiveThis study focuses on the effect of hypothermia on interleukin-1 receptor antagonist pharmacodynamics in a model of neonatal encephalopathy.
methodsThe effect of hypothermia on (i) the tissue concentration of the interleukin-1 receptor antagonist, (ii) the interleukin-1 inflammatory cascade, and (iii) the neuroprotective potential of interleukin-1 receptor antagonist has been assessed on our rat model of neonatal encephalopathy resulting from inflammation induced by bacterial compound plus hypoxia-ischemia.
resultsHypothermia reduced the surface of core and penumbra lesions, as well as alleviated the brain weight loss induced by LPS+HI exposure. Hypothermia compared to normothermia significantly increased (range 50-65%) the concentration of the interleukin-1 receptor antagonist within the central nervous system. Despite this increase of intracerebral interleukin-1 receptor antagonist concentration, the intracerebral interleukin-1-induced tumor necrosis factor-alpha cascade was upregulated. In hypothermic condition, the known neuroprotective effect of interleukin-1 receptor antagonist was neutralized (50 mg/kg/12 h for 72 h) or even reversed (200 mg/kg/12 h for 72 h) as compared to normothermic condition.
conclusionHypothermia interferes with the pharmacodynamic parameters of the interleukin-1 receptor antagonist, through a bioaccumulation of the drug within the central nervous system and a paradoxical upregulation of the interleukin-1 pathway. These effects seem to be at the origin of the loss of efficiency or even toxicity of the interleukin-1 receptor antagonist when combined with hypothermia. Such bioaccumulation could happen similarly with the use of other drugs combined to hypothermia in a clinical context.
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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.