Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of Critical Care Medicine, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Brain Res Bull. 2021 Aug;173:97-107. doi: 10.1016/j.brainresbull.2021.05.014. Epub 2021 May 19.
Cardiac arrest (CA) is the leading cause of death in humans. Research has shown that mild therapeutic hypothermia (MTH) can reduce neurological sequelae and mortality after CA. Nevertheless, the mechanism remains unclear. This study aimed to determine whether MTH promotes neurogenesis, attenuates neuronal damage, and inhibits apoptosis of neurons in rats after CA. Sprague-Dawley rats were divided into the normothermia and mild hypothermia groups. The rats in the normothermia and hypothermia groups were exposed to 2 h of normothermia (36-37℃) and hypothermia (32-33℃), respectively, immediately after resuscitation from 5 min of asphyxial CA. Corresponding control groups not subjected to CA were included. On days 1-6, 5-bromodeoxyuridine (BrdU) 100 mg/kg/day was administered intraperitoneally. The animals were euthanized 1 week after CA. Compared with the normothermia group, the hypothermia group showed a significant increase in the number of doublecortin (DCX) immune-positive cells in the subgranular zone of the hippocampus 1 week after CA. Neurogenesis was assessed using double immunofluorescent labeling of BrdU with neuronal-specific nuclear protein (NeuN)/DCX. There was no marked change in the number of newborn mature (BrdU+-NeuN+) neurons, though there was a significant increase in the number of newborn immature (BrdU+-DCX+) neurons in the hypothermia than in the normothermia group 1 week after CA. Neuronal injury and apoptosis in the CA1 region of the hippocampus, assessed using NeuN immunofluorescence and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays, were significantly reduced in the hypothermia group 1 week after CA. Moreover, mild hypothermia increased the expression of cold-shock protein RNA-binding motif protein 3 (RBM3) in the early stage (24 h/48 h) after CA. These results suggested that mild hypothermia promotes generation of neuronal cells, reduces neuronal injury, and inhibits apoptosis of neurons, which may be related to RBM3 expression.
心脏骤停（CA）是人类死亡的主要原因。研究表明，轻度治疗性低温（MTH）可降低 CA 后的神经后遗症和死亡率。然而，其机制尚不清楚。本研究旨在确定 MTH 是否能促进大鼠 CA 后神经发生、减轻神经元损伤和抑制神经元凋亡。SD 大鼠分为常温组和亚低温组。常温组和亚低温组大鼠在复律后分别暴露于 2 小时常温（36-37℃）和亚低温（32-33℃），复律前进行 5 分钟窒息性 CA。同时设立未行 CA 的相应对照组。在 1-6 天，每天给予腹腔注射 5-溴脱氧尿苷（BrdU）100mg/kg。CA 后 1 周处死动物。与常温组相比，亚低温组 CA 后 1 周海马齿状回颗粒下层 DCX 免疫阳性细胞数明显增加。神经发生通过 BrdU 与神经元特异性核蛋白（NeuN）/DCX 的双重免疫荧光标记来评估。新生成熟（BrdU+-NeuN+）神经元数量无明显变化，但亚低温组 CA 后 1 周新生未成熟（BrdU+-DCX+）神经元数量明显增加。CA 后 1 周，海马 CA1 区神经元损伤和凋亡通过 NeuN 免疫荧光和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记测定评估，亚低温组明显减少。此外，亚低温在 CA 后早期（24 小时/48 小时）增加冷休克蛋白 RNA 结合基序蛋白 3（RBM3）的表达。这些结果表明，亚低温促进神经元细胞的生成，减少神经元损伤，抑制神经元凋亡，这可能与 RBM3 的表达有关。
