Therapeutic hypothermia is the standard of clinical care for moderate neonatal hypoxic-ischemic encephalopathy. We investigated the independent and interactive effects of hypoxia-ischemia (HI) and temperature on neuronal survival and injury in basal ganglia and cerebral cortex in neonatal piglets. Male piglets were randomized to receive HI injury or sham procedure followed by 29 h of normothermia, sustained hypothermia induced at 2 h, or hypothermia with rewarming during fentanyl-nitrous oxide anesthesia. Viable and injured neurons and apoptotic profiles were counted in the anterior putamen, posterior putamen, and motor cortex at 29 h after HI injury or sham procedure. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) identified genomic DNA fragmentation to confirm cell death. Though hypothermia after HI preserved viable neurons in the anterior and posterior putamen, hypothermia prevented neuronal injury in only the anterior putamen. Hypothermia initiated 2 h after injury did not protect against apoptotic cell death in either the putamen or motor cortex, and rewarming from hypothermia was associated with increased apoptosis in the motor cortex. In non-HI shams, sustained hypothermia during anesthesia was associated with neuronal injury and corresponding viable neuron loss in the anterior putamen and motor cortex. TUNEL confirmed increased neurodegeneration in the putamen of hypothermic shams. Anesthetized, normothermic shams did not show abnormal neuronal cytopathology in the putamen or motor cortex, thereby demonstrating minimal contribution of the anesthetic regimen to neuronal injury during normothermia. We conclude that the efficacy of hypothermic protection after HI is region specific and that hypothermia during anesthesia in the absence of HI may be associated with neuronal injury in the developing brain. Studies examining the potential interactions between hypothermia and anesthesia, as well as with longer durations of hypothermia, are needed.

中文翻译：

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缺氧缺血和低体温独立和交互影响具有短期恢复能力的新生仔猪的神经元病理。

低温治疗是中度新生儿缺氧缺血性脑病的临床治疗标准。我们调查了缺氧缺血（HI）和温度对新生仔猪基底节和大脑皮层神经元存活和损伤的独立和交互作用。将雄性仔猪随机接受HI损伤或假手术，随后进行29 h的常温，2 h诱导的持续低温或在芬太尼一氧化二氮麻醉期间复温的低温。在HI损伤或假手术后29 h，计数前壳，后壳和运动皮层的存活和受损神经元和凋亡分布。末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）鉴定了基因组DNA片段以确认细胞死亡。尽管HI后的低温治疗在前和后壳中保留有活力的神经元，但是低温仅在前壳中阻止了神经元的损伤。损伤后2小时开始的低体温不能预防核壳层或运动皮层中凋亡细胞的死亡，而从体温过低引起的温升与运动皮层中凋亡的增加有关。在非HI毛囊中，麻醉期间持续的体温过低与神经元损伤以及前壳和运动皮层中相应的存活神经元丢失有关。TUNEL证实低温假性腐烂壳核的神经变性增加。麻醉的常温other毛在核壳或运动皮层中未显示异常的神经元细胞病理学，从而证明麻醉疗法对常温过程中神经元损伤的贡献最小。我们得出的结论是，HI后的低温保护功效是区域特异性的，并且在没有HI的情况下麻醉期间的体温过低可能与发育中的大脑神经元损伤有关。需要进行研究，以检查低温与麻醉之间的潜在相互作用以及低温持续时间较长的情况。