经颅重频磁刺激对大鼠脑缺血损伤早期运动皮质兴奋性和神经功能的影响

背景目前认为经颅重频磁刺激对局部脑血流,代谢,神经递质,及神经组织损伤后再塑形等均有调节作用.缺血性脑卒中的预后与损伤同侧和对侧的皮质功能重建有关,经颅重频磁刺激能否对脑缺血后皮质功能有影响,起到保护缺血神经元、促进运动功能恢复的作用?目的观察经颅重频磁刺激对大鼠脑缺血再灌注损伤早期运动皮质兴奋性和神经功能的影响.设计完全随机设计.单位中国协和医科大学北京协和医院神经电生理实验室.材料实验于2004-01/06在北京协和医院实验动物中心完成.健康雄性成年Wistar大鼠22只被随机分成实验组和对照组各11只.方法造模前测定Wistar大鼠正常情况下右后肢运动阈值(平均运动阈值为最大输出的22%),测定后两组动物均制作左侧大脑中动脉栓塞1 h再灌注72 h模型,对照组不干预,实验组在再灌注即刻,再灌注后12,36,60 h分别给予经颅重频磁刺激(20 Hz,40%最大输出,每序列5 s,序列间隔2 min,共10个序列),末次刺激4 h后再次测定两组大鼠的运动阈值.于再灌注24和72 h时,以姿势反射实验(0分为无明显肢体瘫痪,5分为昏迷,1～3分纳入实验)和前肢放置实验(0肢体动作迅速完全;1肢体动作缓慢,不完全,＞2 s;2无肢体动作)进行神经功能评分.再灌注72 h麻醉状态下处死取脑,计算脑梗死体积.主要观察指标①两组动物损伤前后的运动阈值.②再灌注24,72 h时的神经功能评分.③再灌注72 h时脑梗死体积.结果13只大鼠进入结果分析.①运动阈值损伤前实验组和对照组无显著差异.损伤后对照组为实验组的1.49倍,但无统计学差异(41.62±24.73)%,(28.00±9.35)%,t=-1.17,P=0.27].②神经功能评分实验组和对照组损伤24 h时无差异(P=0.46);损伤72 h时,实验组显著低于对照组(1.60±1.52,7.75±3.62,t=-3.57,P=0.004).③脑梗死体积损伤72 h时,对照组、实验组分别为(62.00±60.88),(20.00±12.41)mm3,做对数转换后比较无差异(t=-1.31,P=0.22),但若将数据做Log10(梗死体积)]转换后有显著性差异(P=0.045).结论①高频、高强经颅重频磁刺激可能参与维持脑缺血再灌注损伤后运动阈值的稳定,防止运动阈值过度升高而干扰运动功能的恢复.②经颅重频磁刺激可能缓解脑缺血再灌注损伤后的神经功能障碍,随损伤时间延长,效应越明显.③经颅重频磁刺激可能缩小脑梗死体积.

Effects of repetitive transcranial magnetic stimulation on motor cortical excitability and neural function of rats in early period after cerebral ischemia injury

BACKGROUND: It is believed that repetitive transcranial magnetic stimulation (rTMS) may produce such neurophysiological effects as regulating regional cerebral blood flow, neurotransmitters, local metabolism, and neuronal remodeling after nerve tissue injuries. The prognosis ofischemic stroke is related with the cortical function reconstruction in the ipsilateral and contralateral hemisphere of the lesion. Currently studies have not defined whether rTMS can affect the cortical function, protect ischemic neurons and promote motor functional recovery after cerebral ischemia.OBJECTIVE: To investigate the effects of rTMS on rat motor cortical excitability and neural function in acute stage of cerebral ischemia-reperfusion injury.DESIGN: Completely randomized experiment.SETTING: Electroneurophysiological Laboratory of Peking Union Medical College Hospital.MATERIALS: The experiment was completed in the Zoological Research Center of Peking Union Hospital from January to June 2004. Totally 22adult male healthy Wistar rats were randomly divided into treatment group and the control group with 11 in each.METHODS: After determination of the average motor threshold of the right hind limbs, which was 22% of the maximum output, the rats were subjected to middle cerebral artery occlusion for 1 hour followed by reperfusion for 72 hours. At each time point of immediately and at 12, 36 and 60 hours after the initiation of reperfusion, the rats in the treatment group received rTMS treatment (20 Hz, 40% maximum output, 5 seconds for each session with an between-session interval of 2 minutes for a total of 10 sessions), and the site for motor threshold evaluation was used for rTMS stimulation; the rats in the control group recevied no treatment after model establishment. Motor threshold testing was performed in both groups 4 hours after the last session of treatment to avoid immediate-early effects of rTMS on the motor threshold. At 24 and 72 hours of reperfusion, the scores of neural function were recorded according to evaluation systems. All the rats with scores between 1 and 3 were enrolled in statistical analysis were evaluated between.MAIN OUTCOME MEASURES: ① Motor threshold of the rats in both groups before and after injury; ② Neural function scores at 24 and 72 hour reperfusion; ③ Infarct volume at 72 hour of reperfusion.RESULTS: Totally 13 rats entered the final result analysis. Before injury,motor threshold in the treatment and control group was similar (P=0.71),and after the injury, the motor threshold of the control group was 1.49times that of the treatment group but such difference was not statistically significant (41.62±24.73)% vs (28.00±9.35)%, t=-1.17, P=0.27]. At 24hours of reperfusion, the functional scores of the treatment group and control group were not significantly different (P=0.46), but at 72 hours, the scores of the treatment group were significantly lower than that of the control group (1.60±1.52 vs 7.75±3.62, t=-3.57, P=0.004). The average infarct volume of two groups was (62.00±60.88) mm3 and (20.00±12.41) mm3 at 72 hours of reperfusion, respectively, which, after logarithm transformation,was not significantly different between the two group (t=-1.31, P=0.22),but when the infarct volume was transformed into Log10 values, a significant difference occurred between them (P=0.045).CONCLUSION: rTMS may stabilize and prevent the increment of the motor threshold, time-dependently relieve the neural function disability and reduce the infarct volume after cerebral ischemia-reperfusion injury.