CAJ | 학술논문

目的观察高频重复经颅磁刺激(rTMS)对全脑缺血再灌注大鼠空间记忆能力及海马长时程增强(LTP)的影响,探讨rTMS是否通过增强LTP促进模型大鼠空间记忆能力的恢复.方法雄性Wistar大鼠83只,5只测定磁刺激运动诱发电位静息阈值,将余78只大鼠按随机数字表法分成正常组、模型组(制作脑缺血再灌注模型)和rTMS组(制作脑缺血再灌注模型,然后给予rTMS治疗).用四血管夹闭法制作全脑缺血再灌注10 min模型；术后第3天开始给予rTMS(10 Hz,静息阈值,刺激5 s),每天2次,连续刺激14 d；分别在术前、术后3d、术后17d(即rTMS治疗14d)后,用Morris水迷宫检测大鼠空间学习记忆能力,电生理检测大鼠在体海马穿通纤维到齿状回颗粒细胞层(PP-DG)电刺激诱发电位(兴奋性突触后电位、群峰电位)及θ波短脉冲群电刺激LTP诱导幅度的变化.结果术后第3天,模型大鼠PP-DG通路LTP诱发电位幅度较正常组显著降低,模型组与rTMS组间差异无统计学意义(P＞0.05)；治疗14 d后,PP-DG通路LTP诱发电位幅度正常组、模型组和rTMS组之间组间差异有统计学意义(P＜ 0.05)；Morris水迷宫实验显示大鼠定位航行逃避潜伏期和空间探索在原平台所在象限时间及穿越平台位置时间的组间差异有统计学意义(P＜0.01),rTMS组逃避潜伏期显著缩短(P ＜0.01)；rTMS组在原平台所在象限时间及穿越平台时间较模型组明显增多(P＜0.01).结论高频rTMS能促进全脑缺血再灌注后大鼠空间学习记忆能力的恢复,其作用主要是通过增强海马LTP的诱导幅度,原因可能与rTMS能调节海马环路中间神经元功能状态及长期高频rTMS可增强神经递质的释放有关.
목적 관찰고빈중복경로자자격(rTMS)대전뇌결혈재관주대서공간기억능력급해마장시정증강(LTP)적영향,탐토rTMS시부통과증강LTP촉진모형대서공간기억능력적회복.방법 웅성Wistar대서83지,5지측정자자격운동유발전위정식역치,장여78지대서안수궤수자표법분성정상조、모형조(제작뇌결혈재관주모형)화rTMS조(제작뇌결혈재관주모형,연후급여rTMS치료).용사혈관협폐법제작전뇌결혈재관주10 min모형；술후제3천개시급여rTMS(10 Hz,정식역치,자격5 s),매천2차,련속자격14 d；분별재술전、술후3d、술후17d(즉rTMS치료14d)후,용Morris수미궁검측대서공간학습기억능력,전생리검측대서재체해마천통섬유도치상회과립세포층(PP-DG)전자격유발전위(흥강성돌촉후전위、군봉전위)급θ파단맥충군전자격LTP유도폭도적변화.결과 술후제3천,모형대서PP-DG통로LTP유발전위폭도교정상조현저강저,모형조여rTMS조간차이무통계학의의(P＞0.05)；치료14 d후,PP-DG통로LTP유발전위폭도정상조、모형조화rTMS조지간조간차이유통계학의의(P＜ 0.05)；Morris수미궁실험현시대서정위항행도피잠복기화공간탐색재원평태소재상한시간급천월평태위치시간적조간차이유통계학의의(P＜0.01),rTMS조도피잠복기현저축단(P ＜0.01)；rTMS조재원평태소재상한시간급천월평태시간교모형조명현증다(P＜0.01).결론 고빈rTMS능촉진전뇌결혈재관주후대서공간학습기억능력적회복,기작용주요시통과증강해마LTP적유도폭도,원인가능여rTMS능조절해마배로중간신경원공능상태급장기고빈rTMS가증강신경체질적석방유관.
Objective To investigate the effects of repeated high frequency transcranial magnetic stimulation (rTMS) on spatial learning and memory function,and on long-term potentiation (LTP) after global cerebral ischemia and reperfusion,and to explore the mechanisms involved.Methods Eighty-three male Wistar rats were studied.Five were tested to determine their average motor threshold (Tm).The others were divided into a normal control group,a cerebral ischemia and reperfusion model group and an rTMS group.Cerebral ischemia was induced with the four vessel occlusion method for 10 minutes.The rTMS treatment protocol (10 Hz stimulation for 5 s at the resting threshold,twice a day) was applied over a 2-week period from day 3 post-operation.The Morris water maze test was performed to observe spatial learning and memory at post-operation day 2 and day 4.The field excitatory postsynaptic potentials,population spike and the magnitude of long-term potentiation (LTP) induced by theta burst electric stimulation were recorded from the perforant path to the dentate gyrus (PP-DG).Results At post-operation day 3,rats in the untreated cerebral ischemia and reperfusion model group exhibited a significant decrease in the magnitude of the PP-DG LTP as compared to the normal group.No significant difference in LTP was found between the model group and the rTMS group.After the 2 weeks of treatment the LTP levels in the rTMS treated group were significantly higher than in the two untreated groups.In the Morris water maze testing,the average escape latency in the rTMS group was significantly shorter than that of the cerebral ischemia and reperfusion model group (which was not treated).In the probe trials,the time in the original quadrant of the platform and the time of crossing the platform were both significantly less for the rTMS-treated rats than for those not treated.Conclusions High frequency rTMS can improve spatial learning and memory after global cerebral ischemia and reperfusion by enhancing the LTP induced in the hippocampus.High frequency rTMS might exert this beneficial effect by modulating the function of intermediate neurons in the hippocampal neuronal network and by promoting neurotransmitter release.