Decreased Population Spike in CA1 Hippocampal Area of Adrenalectomized Rats after Repeated Synaptic Stimulation

Population spikes, evoked in the CA1 hippocampal area by stimulation of the Schaffer collaterals at various intensities, were recorded over a period of 70 min in slices from 7-day adrenalectomized (ADX) or sham-operated rats. Slices from sham-operated rats with intermediate plasma corticosterone levels (between 0.5 and 5μg corticosterone/100 ml plasma) at the start of the experiment displayed very stable synaptic responses. However, the responses recorded in slices from rats with lower or higher corticosterone levels gradually declined, with repeated stimulation. Similarly, a significant decline of the population spike over time was observed in slices from ADX rats, particularly with low stimulus intensities; characteristics of the compound EPSP were much more stable. The decline of the population spike amplitude was alleviated when: 1) single rather than repeated stimulation was applied; 2) the experiments were performed in the presence of 20 mM glucose; or, 3) moderately high (10^?8 or 10^?7 M) concentrations of corticosterone were administered in vitro; low (10^?9 M) or high (10^?6 M) corticosterone concentrations in vitro did not improve the stability of the synaptic response in slices from ADX rats. These data suggest that intermediate levels of corticosterone are necessary to maintain the stability of the Schaffer collateral input to CA1 neurons. With very low or high corticosterone levels, CA1 neurons apparently fail to respond to synaptic stimulation, over time. The possible mechanisms underlying this bell-shaped dose response curve for corticosterone are discussed.     

重复经颅磁刺激治疗卒中后认知障碍的研究进展

认知障碍是卒中后常见并发症,严重影响患者康复进程及生活质量。重复经颅磁刺激（repetitive transcranial magnetic stimulation,rTMS）作为一种新型的非侵入性神经电生理技术,通过改变神经细胞动作电位影响脑内代谢和神经电活动,近年来逐渐被用于卒中后认知障碍的治疗。目前rTMS在卒中后执行功能、记忆功能、语言能力及视空间能力的康复应用中均取得了较为积极的疗效,且在指南推荐的治疗参数范围内操作基本是安全的,但仍缺乏大样本、多中心、高质量的随机对照试验进一步明确其最佳刺激参数与治疗效果。rTMS治疗卒中后认知障碍的研究仍处于探索阶段,未来有望进行更深入的机制研究,为rTMS治疗卒中后认知功能障碍提供更切实有力的依据。     

Effectiveness of Repetitive Transcranial Magnetic Stimulation on Fibromyalgia Patients Responding to a First Repetitive Transcranial Magnetic Stimulation Induction Course After Six Months of Maintenance Treatment: A Randomized Pilot-Controlled Study

BackgroundFibromyalgia is a chronic painful condition without real, effective treatment. The administration of repetitive transcranial magnetic stimulation (rTMS) has been shown to have a therapeutic effect on pain, but there are still questions about the maintenance of its effect over time. Continuation of the treatment upon clinical response through maintenance sessions is promising and merits further exploration.Materials and MethodsWe conducted a randomized, parallel-group, controlled study involving 78 patients to evaluate the effect of rTMS vs sham stimulation after a three-week induction treatment and six months of maintenance treatment (three-week periodicity) on 22 patients who presented a clinical response to the induction treatment. The clinical response was defined as a ≥30% decrease of the baseline visual analog scale (VAS) for pain and a score for the Patient Global Impression of Change (PGIC) >5. The clinic global impression, fibromyalgia impact questionnaire, symptom severity score, and Beck’s depression inventory were also studied.ResultsA significant clinical response to treatment with rTMS was observed after the induction phase and maintained over six months, particularly as measured by the PGIC parameter of pain, as well as of the intensity of fatigue and depression, with an absence of adverse effects induced by this method.ConclusionA three-week rTMS treatment, characterized by a reduction in pain, as evaluated by VAS, should be continued with the administration of rTMS maintenance sessions for an additional six months to maintain the best possible long-term effects.     

盐酸多奈哌齐对血管性痴呆小鼠海马CA1区Calpain 1表达的影响

目的 探讨盐酸多奈哌齐对反复脑缺血-再灌注后血管性痴呆(VaD)小鼠海马CA1区Calpain 1表达的影响.方法 采用双侧颈总动脉反复缺血-再灌注合并尾端放血的方法制备VaD动物模型.分别于术后第4周和第8周测试小鼠的学习和记忆成绩,应用免疫组化方法观察海马CA1区Calpain 1表达的变化及盐酸多奈哌齐对其的影响.结果 术后4周和8周时模型组小鼠的学习、记忆成绩均明显劣于假手术组小鼠(P<0.01),海马CA1区Calpain 1表达分别是(0.090 0±0.010 0)和(0.102 0±0.008 4),显著高于假手术组的(0.033 2±0.004 3)和(0.031 7±0.004 6)(P<0.01).多奈哌齐治疗组小鼠在术后4周和8周时学习记忆能力较模型组显著改善(P<0.01),海马CA1区Calpain 1表达各为(0.052 0±0.008 4)和(0.068 0±0.008 4),显著低于模型组小鼠(P<0.05).结论 Calpain 1可能参与了脑缺血再灌注后小鼠VaD的发生,盐酸多奈哌齐改善VaD小鼠学习和记忆的能力可能与其减少Calpain 1表达有关.     

低频重复经颅磁刺激的抗作用及其对癫大鼠海马CA3区膜连蛋白A7表达的影响

目的:观察低频重复经颅磁刺激(rTMS)对大鼠性发作行为及海马CA3区膜连蛋白A7表达的影响。方法:取85只健康雄性SD大鼠,按预处理方式将其分成rTMS组(rTMS刺激+毛果芸香碱致)、对照组(假刺激+毛果芸香碱致)及生理盐水对照组(假刺激+生理盐水)。各组大鼠经相应处理后,rTMS组和对照组(各n=30)大鼠制作氯化锂-毛果芸香碱癫持续状态(SE)模型;生理盐水对照组(n=25)则腹腔注射生理盐水。观察各组大鼠行为表现及SE潜伏期,应用免疫组化法观察膜连蛋白A7表达的动态变化(6 h、24 h、1周、3周、6周)。结果:①rTMS组SE潜伏期为(41.37±5.45)min,与对照组(23.86±4.42)min比较明显延长(P<0.01);②海马CA3区膜连蛋白A7阳性细胞数在各时间点均为对照组最多,rTMS组次之,生理盐水对照组最少(均P<0.05)。但是膜连蛋白A7的表达随时间变化的趋势rTMS组与对照组明显不同。结论:低频rTMS有一定抗作用;低频rTMS可影响大鼠海马CA3区膜连蛋白A7表达并呈现独特的动态变化特点。     

经颅重频磁刺激对大鼠脑缺血再灌流损伤早期运动皮层兴奋性和神经功能的影响

目的 观察经颅重频磁刺激（rTMS）对大鼠脑缺血再灌流损伤早期运动皮层兴奋性和神经功能的影响。方法测定Wistar大鼠右后肢运动阚值（MT）．制作左侧大脑中动脉栓塞（MCAO）再灌流模型．给予rTMS（1次／d）。再灌流72h处死取脑。比较大鼠MCAO再灌流损伤不同时间MT、神经功能评分，脑梗死体积的变化及rTMS的影响。结果MCAO再灌流损伤使大鼠出现局灶性梗死灶，MT升高；神经功能障碍且其程度随损伤时间延长而愈加明显．表现为功能评分升高；rTMS可改善大鼠MCAO再灌流损伤72h的MT和功能障碍程度。减小梗死体积。尤其改善神经功能障碍的程度与对照组比较差异有显著性（P=0．004）。结论rTMS可能对早期缺血脑组织有保护作用．对缺血性脑卒中有进一步研究、应用前景。     

Updated Review on the Clinical Use of Repetitive Transcranial Magnetic Stimulation in Psychiatric Disorders

With the ability to modulate cortical activity,repetitive transcranial magnetic stimulation(r TMS) is becoming increasingly important in clinical applications for psychiatric disorders. Previous studies have demonstrated its promising efficacy in depression and schizophrenia, and emerging evidence has also been found in patients with anxiety disorder, obsessive–compulsive disorder, and substance or food craving. However, the overall literature features some conflicting results, varied quality of studies,and a lack of consensus on optimal r TMS parameters.Besides, the efficacy of r TMS in patients with medicationresistant symptoms has drawn most attention from clinicians. Here we review multi-site studies and double-blind randomized controlled trials(RCTs) in single sites, as well as meta-analyses of RCTs in the last three years, in order to update evidence on efficacy and the optimal protocol of r TMS in psychiatric disorders, especially for medicationresistant symptoms.     

Placebo Response in Repetitive Transcranial Magnetic Stimulation Trials of Treatment of Auditory Hallucinations in Schizophrenia: A Meta-Analysis

Several meta-analyses have assessed the response of patients with schizophrenia with auditory verbal hallucinations (AVH) to treatment with repetitive transcranial magnetic stimulation (rTMS); however, the placebo response has never been explored. Typically observed in a therapeutic trial, the placebo effect may have a major influence on the effectiveness of rTMS. The purpose of this meta-analysis is to evaluate the magnitude of the placebo effect observed in controlled studies of rTMS treatment of AVH, and to determine factors that can impact the magnitude of this placebo effect, such as study design considerations and the type of sham used.The study included twenty-one articles concerning 303 patients treated by sham rTMS. A meta-analytic method was applied to obtain a combined, weighted effect size, Hedges’s g. The mean weighted effect size of the placebo effect across these 21 studies was 0.29 (P < .001). Comparison of the parallel and crossover studies revealed distinct results for each study design; placebo has a significant effect size in the 13 parallel studies (g = 0.44, P < 10⁻⁴), but not in the 8 crossover studies (g = 0.06, P = .52). In meta-analysis of the 13 parallel studies, the 45° position coil showed the highest effect size. Our results demonstrate that placebo effect should be considered a major source of bias in the assessment of rTMS efficacy. These results fundamentally inform the design of further controlled studies, particularly with respect to studies of rTMS treatment in psychiatry.Key words: rTMS, placebo, schizophrenia, auditory hallucination, meta-analysis, sham coil     

Treatment of Alzheimer's Disease with Repetitive Transcranial Magnetic Stimulation Combined with Cognitive Training: A Prospective,Randomized, Double-Blind,Placebo-Controlled Study

MethodsA prospective, randomized, double-blind, placebo-controlled study was performed with 27 AD patients (18 and 8 in the treatment and sham groups, respectively, and 1 drop-out). The participants were categorized into mild [Mini-Mental State Examination (MMSE) score=21-26] and moderate (MMSE score=18-20) AD groups. The rTMS protocols were configured for six cortical areas (both dorsolateral prefrontal and parietal somatosensory associated cortices and Broca''s and Wernicke''s areas; 10 Hz, 90-110% intensity, and 5 days/week for 6 weeks). Neuropsychological assessments were performed using the AD Assessment Scale-cognitive subscale (ADAS-cog), Clinical Global Impression of Change (CGIC), and MMSE before, immediately after, and 6 weeks after the end of rTMS-COG treatment.ResultsData from 26 AD patients were analyzed in this study. There was no significant interactive effect of time between the groups. The ADAS-cog score in the treatment group was significantly improved compared to the sham group (4.28 and 5.39 in the treatment group vs. 1.75 and 2.88 in the sham group at immediately and 6 weeks after treatment, respectively). The MMSE and CGIC scores were also improved in the treatment group. Based on subgroup analysis, the effect of rTMS-COG was superior for the mild group compared to the total patients, especially in the domains of memory and language.ConclusionsThe present results suggest that rTMS-COG represents a useful adjuvant therapy with cholinesterase inhibitors, particularly during the mild stage of AD. The effect of rTMS-COG was remarkable in the memory and language domains, which are severely affected by AD.     

经颅磁刺激对短暂性大脑中动脉闭塞大鼠突触素表达和超微结构改变的影响

目的：研究经颅磁刺激（TMS）对短暂性大脑中动脉闭塞（MCAO）大鼠突触素表达和超微结构改变的影响。方法：TMS组与假刺激组成年大鼠各32只，于MCAO／再灌注（MCAO／R）120min后3周内接受TMS与假刺激处理。在处理不同时间段榆测梗死灶周围突触素（SY38）免疫阳性产物表达，透射电镜下观察刺激21d后缺血侧脑皮质缺血半暗带血管、神经细胞和突触变化。另设正常组6只，假手术组6只，检测脑内SY38免疫阳性产物表达。结果：在刺激1d和3d后，两组SY38免疫阳性物质表达均持续降低，刺激7d后逐渐恢复升高。与假刺激组各对应点相比，TMS组在刺激7d、14d和21d后梗死灶周围SY38免疫阳性物质表达显著增高（P〈0．05）。透射电子显微镜观察提示，刺激21d后TMS组的神经元整体细胞超微结构缺血性损伤好于假刺激组，线粒体肿胀程度较轻，血管周围结构紧密完整，突触界面曲率相对更大，突触间隙变窄，突触后致密物质增厚。结论：长程TMS可以上调脑梗死周围区SY38的表达，减轻缺血周围区毛细血管和神经组织损伤，促进突触超微结构的重建和功能增强，提示TMS有助于促进缺血脑损伤的恢复，促进脑组织神经网络重建和脑可塑性增加是其可能的机制之一。     

低频重复经颅磁刺激对帕金森病患者运动皮质兴奋性的影响探讨

目的:观察低频重复经颅磁刺激(rTMS)对帕金森病(PD)患者大脑皮质兴奋性的影响,并从电生理角度进一步探索PD的发病机制。方法:用1HzrTMS技术治疗3 0例PD患者共10d ,另选择15例PD患者为假刺激组,15名健康者为对照组。采用静息态阈值(RT)、中枢传导时间(CMCT)、中枢静息期(CSP)和运动诱发电位(MEP)的波幅作为评定大脑皮质兴奋性的指标。结果:①PD患者的RT、CMCT和CSP较正常对照组明显降低或缩短,而MEP波幅无变化。治疗组治疗后RT增加,CMCT和CSP延长接近正常,与对照组比已无显著差别,但假刺激组没有变化。②以强直症状为主和以震颤症状为主的PD患者其RT、CMCT、CSP和MEP波幅无明显差别。③将PD患者按UPDRS评分的不同分为轻、中、重3种,分别就RT、CMCT、CSP和MEP波幅进行比较,其差别无显著性差异。结论:PD患者大脑皮质兴奋性升高,低频rTMS可部分抑制这种改变,但TMS对评定早期PD患者大脑皮质兴奋性尚不敏感。     

高低频重复经颅磁刺激治疗卒中后上肢痉挛的对照研究

目的 探讨高、低频重复经颅磁刺激（repetitive transcranial magnetic stimulation,rTMS）大脑初级运动皮层（M1区）治疗卒中后上肢痉挛的临床疗效及差异。      

金纳多对血管性痴呆大鼠认知功能及生长抑素表达的影响

目的研究金纳多对血管性痴呆(vascular dementia,VD)大鼠认知功能及生长抑素(SS)表达的影响。方法采用结扎双侧颈总动脉方法制备慢性前脑缺血动物模型。将100只老龄大鼠随机分为假手术组、模型组和金纳多组。应用水迷宫及免疫组化方法对各组大鼠学习记忆及SS表达进行观察。结果模型组与假手术组学习记忆能力差异有统计学意义(P<0.05);与模型组比较,金纳多治疗30 d后大鼠学习记忆能力明显改善(P<0.05),SS阳性神经元表达增加(P<0.05)。结论金纳多可增加SS阳性神经元表达,改善VD大鼠学习记忆能力。     

Repetitive Transcranial Magnetic Stimulation for the Treatment of Lower Limb Dysfunction in Patients Poststroke: A Systematic Review with Meta-Analysis

PurposeTo investigate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in recovery of lower limb dysfunction in patients poststroke.Participants and MethodsCochrane Central Register of Controlled Trials, Medline, ISI web of knowledge, EBSCO, Embase, Cumulative Index to Nursing and Allied Health Literature and Scopus.ResultsFifteen trials with 385 patients were included. Results showed that rTMS had a significant effect on balance (standard mean difference [SMD] = .38; 95% confidence interval [CI], .07: .69; I² = 51%) and mobility (SMD: ?.67; 95% CI, ?1.08: ?.26; I² = 72%). However, rTMS had no significant immediate effects on the lower limb subscale of the Fugl-Meyer Assessment (FMA-L) (SMD = .01; 95% CI, ?.29: .31; I² = 0%). Continued effects of rTMS was also found to be significant during the follow-up period (SMD = .46; 95% CI, .09: .84; I² = 14%).ConclusionrTMS was found to result in positive effects on mobility, balance and long-term prognosis of FMA-L. However data indicated that there is insufficient evidence for the effectiveness of rTMS in improving lower limb function.