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

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

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 k Pa)。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,m NSS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m NSS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Brd U阳性细胞数及Brd U/Neu N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Brd U/Neu N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。

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.