HOSHINO TAKAO    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Assistant Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Therapeutic hypothermia achieves neuroprotection via a decrease in acetylcholine with a concurrent increase in carnitine in the neonatal hypoxia-ischemia.
Journal	Formal name：Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Abbreviation：J Cereb Blood Flow Metab ISSN code：(1559-7016)0271-678X(Linking)
Domestic / Foregin	Foregin
Volume, Issue, Page	35(5),pp.794-805
Author and coauthor	Takenouchi Toshiki, Sugiura Yuki, Morikawa Takayuki, Nakanishi Tsuyoshi, Nagahata Yoshiko, Sugioka Tadao, Honda Kurara, Kubo Akiko, Hishiki Takako, Matsuura Tomomi, Hoshino Takao, Takahashi Takao, Suematsu Makoto, Kajimura Mayumi
Publication date	2015/05
Summary	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.
DOI	10.1038/jcbfm.2014.253
PMID	25586144