大鼠幼年期轻型颅脑损伤对成年期学习记忆功能的影响

Effect of Mild Traumatic Brain Injury during Pediatric Stage on Cognitive Function in Adult Rats

目的探讨大鼠幼年期轻型颅脑损伤(mild traumatic brain injury,mTBI)对成年期学习记忆功能的影响及其机制。方法将120只幼年期(4周龄)SD大鼠随机分为3组:正常组、假手术组和mTBI组,每组40只。应用液压冲击法制作大鼠mTBI模型。伤后1、4、8、12周,应用水迷宫试验检测大鼠学习记忆功能。伤后30 min、6 h、24 h、48 h、1周、4周、8周和12周,应用末端脱氧核糖核酸转移酶介导的粘性末端标记法(terminal deoxynucleoitidyl transferasemediated nick end labeling,TUNEL)染色和caspase-3免疫组化染色分析大鼠海马组织细胞凋亡,每组每个时间点5只大鼠。结果水迷宫试验结果显示,正常组大鼠和假手术组大鼠各年龄段的潜伏期差异均无统计学意义(P>0.05),mTBI组各年龄段的潜伏期均较假手术组明显延长(P<0.01)。正常组大鼠和假手术组大鼠海马组织可见少量TUNEL阳性和caspase-3阳性细胞,但是两组各时间点TUNEL阳性细胞和caspse-3阳性细胞差异均无统计学意义(P>0.05);mTBI组各时间点大鼠海马组织TUNEL阳性细胞和caspase-3阳性细胞均明显增多(P<0.01)。结论大鼠幼年期mTBI导致的认知功能损害是一个长期持续性的过程,与海马组织迟发性进行性神经元凋亡密切相关。

Objective To investigate the effect of mild traumatic brain injury （TBI） in childhood on memory im- pairment in adult rats and its mechanism.Methods One hundred and twenty SD rats aged 4 weeks were randomly divided into normal group （n = 40）, sham-operation group （n = 40） and mTBI group （n = 40）. The memory function was detec- ted by Morris water maze test l, 4, 8 and 12 weeks after injury. The terminal deoxynucleoitidyl transferase-mediated nick end labeling （TUNEL） assay and immunohistochemistry for caspase-3 were performed to detect hippocampus cell apopto- sis 30 minutes, 6 hours,24 hours, 48 hours, 1 week, 4 weeks, 8 weeks and 12 weeks after injury, with 5 rats in each group at each timepoint.Results In Morris water maze test, the latencies in mild TBI group significantly increased com- pared to those in the sham-operation group at any timepoint （P〈0.01）, which were similar to those in the normal group （P〉0.05）. The numbers of TUNEL-positive and caspase-3-positive cells were increased in the mTBI group compared to those in the sham-operation group （P〈0.01）, which were similar to those in the normal group （P〉0.05）. Memory im pairment and hippocampus ceil apoptosis sustained up to the adult stage.Conclusion Mild TBI induces iong-lasting cogni- tive impairment from pediatric to adult stages in rats through the high level of hippocampus cell apoptosis.