三叉神经电刺激对创伤性脑损伤小鼠认知功能障碍的作用

Effect of Cognitive Dysfunction Using Trigeminal Nerve Stimulation in Traumatic Brain Injury Mice

目的:研究三叉神经电刺激(TNS)对脑损伤(TBI)小鼠认知功能的影响,并探索其可能的机制。方法:将60只小鼠随机分成假手术组(sham)、脑损伤组(TBI)、电刺激组(TNS),每组各20只。使用自由落体(Weight-Drop)模型给小鼠造成创伤性脑损伤,损伤后第1 h、24 h给予TNS组术后三叉神经电刺激。造模结束后第48 h,对小鼠进行Morris水迷宫测试,观察其认知功能。使用Western Blot法与免疫荧光技术检测小鼠海马组织自噬标志物微管相关蛋白1A/1B-轻链3(LC3)、小胶质细胞标记物同种异体炎症因子1(AIF-1/Iba1)、淀粉样前体蛋白(APP)的含量。结果:与TBI组小鼠相比,TNS组小鼠的平台穿越次数与目标象限占比时间明显高于TBI组;TNS还明显提高了TBI小鼠的LC3与Iba1水平和降低了TBI小鼠的APP含量。结论:TNS可以改善TBI小鼠的认知能力,可能是通过改善小鼠TBI后急性期的自噬能力,提高小胶质细胞的清除能力,减少APP而实现的。

Objective:To investigate the effect of trigeminal nerve electrical stimulation(TNS)on cognitive dysfunction and to explore the mechanism of it in traumatic brain injury(TBI)mice.Methods:Sixty mice were randomized into three groups:the sham group(sham),the traumatic brain injury group(TBI),the TNS group(TNS),with 20 mice in each.We induced mouse TBI model by a weight-drop device and stimulated the trigeminal nerve in mice using electrode sheets at 1 h and 24 h.48 h after the surgery,we used Morris water maze to test the cognitive function of the mice.The expression level of LC3,Iba1 and amyloid precursor protein(APP)were tested with western blot and immunofluorescence in hippocampus.Results:Compared with the mice in the TBI group,the times of platform crossings and the percentage of time in the target quadrant of mice in the TNS group were significantly better.TNS significantly increased the expression level of LC3 and Iba1 in hippocampus and also reduced the expression level of APP.Conclusion:TNS modulated the cognitive dysfunction of TBI mice.The mechanism probably worked by ameliorating autophagy,improving the phagocytic capability of microglia and reducing Aβ burden during acute phase of TBI.