Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California, USA.
Pediatr Res. 2013 Aug;74(2):170-9. doi: 10.1038/pr.2013.88. Epub 2013 May 24.
Mild brain hypothermia (31-34 °C) after neonatal hypoxia-ischemia (HI) improves neurodevelopmental outcomes in human and animal neonates. Using an asphyxia model with neonatal mice treated with mild hypothermia after HI, we investigated whether (1)H nuclear magnetic resonance (NMR) metabolomics of brain extracts could suggest biomarkers and distinguish different treatments and outcome groups.
At postnatal day 7 (P7), CD1 mice underwent right carotid artery occlusion, 30 min of HI (8% oxygen), and 3.5 h of either hypothermia (31 °C) or normothermia (37 °C). Whole brains were frozen immediately after HI, immediately after 3.5 h of hypothermia or normothermia treatments, and 24 h later. Perchloric acid extractions of 36 metabolites were quantified by 900 MHz (1)H NMR spectroscopy. Multivariate analyses included principal component analyses (PCA) and a novel regression algorithm. Histological injury was quantified after HI at 5 d.
PCA scores plots separated normothermia/HI animals from hypothermia/HI and control animals, but more data are required for multivariate models to be predictive. Loadings plots identified 11 significant metabolites, whereas the regression algorithm identified 6. Histological injury scores were significantly reduced by hypothermia.
Different treatment and outcome groups are identifiable by (1)H NMR metabolomics in a neonatal mouse model of mild hypothermia treatment of HI.
新生儿缺氧缺血性损伤（HI）后轻度脑低温（31-34°C）可改善人类和动物新生儿的神经发育结局。本研究采用新生鼠 HI 后轻度低温治疗的窒息模型，探讨脑提取物的（1）H 核磁共振波谱（NMR）代谢组学是否可以提示生物标志物并区分不同的治疗和结局组。
CD1 小鼠于生后 7 天（P7）行右侧颈总动脉结扎，30 min 缺氧（8%氧气），随后进行 3.5 h 轻度低温（31°C）或常温（37°C）治疗。HI 后立即、3.5 h 低温或常温治疗后立即以及 24 h 后立即将全脑冷冻。采用 900 MHz（1）H NMR 光谱法对 36 种代谢物的高氯酸提取物进行定量分析。多元分析包括主成分分析（PCA）和新的回归算法。HI 后 5 d 行组织学损伤定量。
PCA 得分图可将常温/HI 动物与低温/HI 动物和对照组动物区分开，但需要更多数据才能使多变量模型具有预测性。加载图确定了 11 种有显著意义的代谢物，而回归算法则确定了 6 种。低温可显著降低组织学损伤评分。
在轻度低温治疗 HI 的新生鼠模型中，（1）H NMR 代谢组学可识别不同的治疗和结局组。
