ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2015
Therapeutic hypothermia achieves neuroprotection via a decrease in acetylcholine with a concurrent increase in carnitine in the neonatal hypoxia-ischemia.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Evolution of Energy Related Metabolites in Plasma from Newborns with Hypoxic-Ischemic Encephalopathy during Hypothermia Treatment.Scientific reports · 2017Trial
- Setting standards for brain collection procedures in metabolomic studies.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- L-carnitine: new perspectives on the management of preterm infants.Frontiers in nutrition · 2025Review
- Hypoxic-Ischemic Insult Alters Polyamine and Neurotransmitter Abundance in the Specific Neonatal Rat Brain Subregions.ACS chemical neuroscience · 2024Article
- Targeting the Multiple Complex Processes of Hypoxia-Ischemia to Achieve Neuroprotection.International journal of molecular sciences · 2024Review
- A narrative review on treatment strategies for neonatal hypoxic ischemic encephalopathy.Translational pediatrics · 2023Review
- The hypotaurine-taurine pathway as an antioxidative mechanism in patients with acute liver failure.Journal of clinical biochemistry and nutrition · 2022Article
- Mass Spectrometry Imaging as a New Method: To Reveal the Pathogenesis and the Mechanism of Traditional Medicine in Cerebral Ischemia.Frontiers in pharmacology · 2022Review
- Metabolic adaptations to hypoxia in the neonatal mouse forebrain can occur independently of the transporters SLC7A5 and SLC3A2.Scientific reports · 2021Article
- Metabolomic analysis and mass spectrometry imaging after neonatal stroke and cell therapies in mouse brains.Scientific reports · 2020Article
- Coordination between Calcium/Calmodulin-Dependent Protein Kinase II and Neuronal Nitric Oxide Synthase in Neurons.International journal of molecular sciences · 2020Review
- A New Vision for Therapeutic Hypothermia in the Era of Targeted Temperature Management: A Speculative Synthesis.Therapeutic hypothermia and temperature management · 2019Review
- Quantitative imaging mass spectroscopy reveals roles of heme oxygenase-2 for protecting against transhemispheric diaschisis in the brain ischemia.Journal of clinical biochemistry and nutrition · 2018Article
- Uptake of dendrimer-drug by different cell types in the hippocampus after hypoxic-ischemic insult in neonatal mice: Effects of injury, microglial activation and hypothermia.Nanomedicine : nanotechnology, biology, and medicine · 2017Article
- Plasma metabolite score correlates with Hypoxia time in a newly born piglet model for asphyxia.Redox biology · 2017Article
- Assessment of phospholipid synthesis related biomarkers for perinatal asphyxia: a piglet study.Scientific reports · 2017Article
- 2-Iminobiotin Superimposed on Hypothermia Protects Human Neuronal Cells from Hypoxia-Induced Cell Damage: AnFrontiers in pharmacology · 2017Article
- Neuroprotective Effects of Acetyl-L-Carnitine on Neonatal Hypoxia Ischemia-Induced Brain Injury in Rats.Developmental neuroscience · 2016Article
- Development of an Imaging Mass Spectrometry Technique for Visualizing Localized Cellular Signaling Mediators in Tissues.Mass spectrometry (Tokyo, Japan) · 2015Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although therapeutic hypothermia is known to improve neurologic outcomes after perinatal cerebral hypoxia-ischemia, etiology remains unknown. To decipher the mechanisms whereby hypothermia regulates metabolic dynamics in different brain regions, we used a two-step approach: a metabolomics to target metabolic pathways responding to cooling, and a quantitative imaging mass spectrometry to reveal spatial alterations in targeted metabolites in the brain. Seven-day postnatal rats underwent the permanent ligation of the left common carotid artery followed by exposure to 8% O2 for 2.5 hours. The pups were returned to normoxic conditions at either 38 °C or 30 °C for 3 hours. The brain metabolic states were rapidly fixed using in situ freezing. The profiling of 107 metabolites showed that hypothermia diminishes the carbon biomass related to acetyl moieties, such as pyruvate and acetyl-CoA; conversely, it increases deacetylated metabolites, such as carnitine and choline. Quantitative imaging mass spectrometry demarcated that hypothermia diminishes the acetylcholine contents specifically in hippocampus and amygdala. Such decreases were associated with an inverse increase in carnitine in the same anatomic regions. These findings imply that hypothermia achieves its neuroprotective effects by mediating the cellular acetylation status through a coordinated suppression of acetyl-CoA, which resides in metabolic junctions of glycolysis, amino-acid catabolism, and ketolysis.
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