天津医药

天津医药

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亚低温促进大鼠颅脑创伤后海马新生 神经元长期存活及成熟

王晶 1*，徐超 1*，李晓红 1，涂悦 1，陈翀 1，马铁柱 1，王丽娜 1，朱旭 1，任吉滨 1，许子宁 1，杨慧云 2，张赛 1△   

  1. ：1中国人民武装警察部队后勤学院附属医院颅脑创伤与神经修复研究所（邮编300162）；2天津医科大学生物医学工程学院 *共同第一作者
  • 出版日期:2018-07-15 发布日期:2018-07-15
  • 作者简介:王晶（1991），女，硕士在读，主要从事颅脑创伤相关研究；徐超（1991），男，硕士在读，主要从事颅脑创伤相关研究

Mild hypothermia facilitates the long-term survival and maturation of hippocampal newborn neurons after traumatic brain injury in rats

WANG Jing1, XU Chao1, LI Xiao-hong1, TU Yue1, CHEN Chong1, MA Tie-zhu1, WANG Li-na1, ZHU Xu1, REN Ji-bin1, XU Zi-ning1, YANG Hui-yun2, ZHANG Sai1△   

  1. 1 Tianjin Key Laboratory of Neurotrauma Repair, Institute of Traumatic Brain Injury and Neuroscience, the Affiliated Hospital of Logistics University of Chinese People’s Armed Police Forces, Tianjin 300162, China; 2 School of Biomedical Engineering and Technology of Tianjin Medical University △Corresponding Author E-mail: zhangsai718@vip.126.com
  • Published:2018-07-15 Online:2018-07-15

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摘要： 目的 探讨亚低温（MHT）对大鼠颅脑创伤（TBI）后海马齿状回区（DG）新生神经元长期存活及成熟的影 响。方法 59只健康成年SD大鼠随机分为假手术（sham）组、TBI组及TBI+MHT组，sham组15只，其余两组各22只。 TBI大鼠模型借助液压冲击脑损伤仪建立，打击压力设置为2.0 atm（1 atm=101.325 kPa）。TBI+MHT组大鼠在损伤后 立即接受MHT，降温后直肠目标温度为33.5 ℃，维持4 h，并于1.5 h内缓慢复温至37 ℃。在不同时间点应用Morris水 迷宫试验，mNSS评分比较大鼠神经功能恢复情况，免疫荧光染色等方法检测各组海马新生神经元长期存活及成熟 情况。结果 与TBI组比较，TBI+MHT组大鼠伤后4周的逃避潜伏期明显缩短，平台穿越次数及目标象限停留时间 均显著增加（P＜0.05）。损伤后1、2、4周TBI+MHT组大鼠较TBI组mNSS评分均降低（P＜0.01）。与sham组比较，损 伤后1、4、8周TBI组和TBI+MHT组大鼠损伤侧海马DG区BrdU阳性细胞数及BrdU/NeuN双阳性细胞数均增加（P＜ 0.05），且TBI+MHT组较TBI组增加更明显（P＜0.05）。此外，与损伤后1周相比，损伤后4周及8周TBI组BrdU/NeuN 双阳性细胞数减少，而TBI+MHT组进一步增加（P＜0.05）。结论 MHT可促进TBI后新生神经元的长期存活及成 熟，促进TBI后神经功能恢复。

关键词: 低温, 人工, 颅脑损伤, 海马, 神经元

Abstract: Objective To investigate the effect of mild hypothermia (MHT) in long-term survival and maturation of newborn neurons in the dentate gyrus (DG) of hippocampus after traumatic brain injury (TBI) in rats. Methods Fifty-nine adult Sprague-Dawley (SD) rats were randomly divided into the sham-injured group (n=15), TBI group (n=22) and TBI+ MHT group (n=22). The TBI rat model was established with hydraulic impact brain damage instrument, and the pressure was set at 2.0 atm (1 atm=101.325 kPa). The rats in TBI +MHT group were received MHT after injury, and the rectal target temperature was 33.5 ℃ maintaining 4 h, and then raised the temperature slowly within 1.5 h to 37 ℃. The Morris water maze, modified neurological severity scores (mNSS) and immunofluorescence staining were used at the corresponding time points to observe functional recovery of nervous system and long-term survival and maturation of newborn neurons in hippocampus. Results Morris water maze tests showed that the escape latency was significantly decreased, and the number of platform crossings and the time stayed in the target quadrant were increased at 4 weeks after injury in TBI+MHT group compared with those of TBI group (P＜0.05). Compared with TBI group, mNSS was significantly decreased at 1, 2 and 4 weeks after injury in TBI+MHT group (P＜0.01). Compared with sham group，BrdU-positive cells and BrdU/NeuN doublelabeled cells in rat hippocampal DG were significantly increased at 1, 4 and 8 weeks after injury in TBI group and TBI+MHT group (P＜0.05), and which were increased more obviously in TBI + MHT group than those of TBI group (P＜0.05). Furthermore, the BrdU/NeuN double-labeled cells were further increased at 4 weeks and 8 weeks after injury in TBI+MHT group, and which were decreased in TBI group compared with 1 week after injury (P＜0.05). Conclusion MHT could facilitate not only long-term survival but also maturation of newborn neurons after TBI, and promote the functional recovery of nervous system.

Key words: hypothermia, induced, craniocerebral trauma, hippocampus, neurons