红景天苷对局灶性脑缺血再灌注大鼠神经生长相关蛋白的影响

目的研究红景天苷对局灶性脑缺血/再灌注损伤(I/R)后神经生长蛋白(GAP-43)表达的影响。并探讨其可能的机制。方法Wistar大鼠随机分为假手术组、I/R模型组和红景天苷组,采用线栓法制造大鼠大脑中动脉阻塞/再灌注(MCAO/R)模型,MCAO2h后恢复再灌注。用免疫组化方法检测再灌注后1d、3d、7d、14d、21d的与个时间点GAP-43的表达。结果红景天苷明显减小梗死灶范围,梗死灶周围皮质神经元损伤明显减轻。假手术组中枢神经系统GAP-43表达较少,I/R组GAP-43阳性表达,在术后1d开始增高,3d表达最强,高水平维持到7d,14d明显降低,但未降至正常水平。红景天苷组各个时间点GAP-43阳性表达强度均显著高于I/R对照组(P<0.05)。结论红景天苷能提高脑缺血/再灌注后GAP-43的表达,促进轴突生长,易化脑缺血再灌注损伤后神经可塑性。     

脑缺血再灌注后脑梗塞周围区生长相关蛋白-GAP43表达的变化及外源性神经生长因子的影响

目的研究大鼠脑缺血再灌注后生长相关蛋白-43(GAP-43)表达的变化规律及外源性神经生长因子(NGF)的影响.方法成年健康雌性Wistar大鼠72只,随机分为假手术组、自然恢复组、人工脑脊液组和NGF治疗组.采用线栓法建立大脑中动脉缺血再灌注(MCAO)动物模型,应用免疫组织化学方法观察脑缺血再灌注后GAP-43的表达.结果(1)脑缺血再灌注6 h后,缺血周围区GAP-43表达逐渐增高,第7天达高峰,以后逐渐降低,第21天仍有表达.(2)应用外源性NGF后,GAP-43表达较对照组有所增高,但无显著性差异(P＞0.05).结论提示中枢神经系统损伤后,神经元具有再生和修复的可塑性,外源性NGF对GAP-43的调节有待于进-步研究.     

动脉内脑局部低温联合再灌注治疗急性缺血性卒中大鼠

目的:研究动脉内脑局部低温联合再灌注对急性缺血性卒中(AIS)大鼠脑组织的保护作用及其机制.方法:将雄性SD大鼠随机分为假手术(sham)组、缺血(I,大脑中动脉永久闭塞)组、缺血再灌注(I/R,大脑中动脉闭塞后再灌注)组及低温(H,动脉内脑局部低温联合再灌注)组,每组24只.H组再灌注后经颈内动脉灌注约6.7 mL ...     

缺血再灌注损伤对成年大鼠脑室下区神经干细胞增殖和NMDA受体亚单位2A表达的影响

目的:研究缺血再灌注损伤对成年大鼠脑室下区(SVZ)神经干细胞增殖和NMDA受体亚单位NR2A表达的影响,探讨NR2A在神经干细胞增殖中的作用。方法:正常成年雄性SD大鼠45只,随机分成正常组、假手术组和缺血再灌注组,线栓法制作大脑中动脉栓塞(middle cerebral artery occlusion,MCAO)2 h再灌注模型,术后分3、7、14 d三个时间点取脑。行免疫组织化学染色观察Nestin、增殖细胞核抗原(PCNA)及NMDA受体亚单位NR2A阳性细胞数。结果:(1)各组大鼠SVZ均可见Nestin和PCNA阳性细胞,缺血再灌注后3 d,脑室下区Nestin IOD值和PCNA阳性细胞增加(P0.05),7 d达到高峰(P0.05),14 d后有所下降(P0.05)。(2)各组大鼠SVZ均表达NR2A阳性细胞,缺血再灌注后3 d,NR2A阳性细胞数开始增加(P0.05),7 d也达到高峰(P0.05),14 d阳性细胞数有所下降,但维持较高的水平(P0.05)。(3)缺血再灌注后不同时间点NR2A阳性细胞数与PCNA阳性细胞数有高度正相关性(r=0.985,P0.05)。结论:缺血再灌注损伤能刺激成年大鼠SVZ神经干细胞的增殖;缺血再灌注后NMDA受体亚单位NR2A表达增加,并且与神经干细胞的表达变化趋于一致,因此推断NR2A可能参与缺血再灌注大鼠SVZ神经干细胞的增殖过程。     

高血脂对大鼠脑缺血再灌注损伤后海马内bFGF表达的影响

目的:研究高血脂对大鼠脑缺血再灌注损伤后海马内碱性成纤维细胞生长因子(bFGF)表达的影响。方法:高脂饮食建立高血脂模型。以线栓法制作大鼠大脑中动脉阻塞的局灶性脑缺血再灌注模型,采用蛋白印迹和神经行为学相结合的方法,观察缺血再灌注侧海马内bFGF的表达及其意义。结果:与假手术组比较,脑缺血再灌注组bFGF的表达均增高,其变化趋势均为1 d有所升高,3 d达高峰,7 d后下降。在相同再灌注时间点内与脑缺血再灌注组比较,高血脂合并脑缺血再灌注组bFGF的表达减少。结论:脑缺血再灌注损伤后bFGF的表达是呈动态变化的。高血脂可能影响bFGF的分泌。     

马来酸桂哌齐特对大鼠脑缺血再灌注损伤的保护作用

目的:研究马来酸桂哌齐特对大鼠脑缺血再灌注损伤的神经保护作用。方法:成年雄性大鼠60只,给予线栓法大鼠大脑中动脉阻断(MCAO)后,随机分为马来酸桂哌齐特处理组和生理盐水对照组,观察大鼠的体重变化和死亡情况;再灌注后2 h和7 d对动物进行神经功能评分;7 d时用TTC染色法比较两组脑梗死体积。结果:两组大鼠的体重(P0.05)和总体死亡率(P0.05)无显著差异,但马来酸桂哌齐特能明显降低MCAO 24 h内的死亡率(P0.05);马来酸桂哌齐特能够显著改善MCAO损伤的神经功能评分,并可明显减少脑梗死体积百分比(P0.05)。结论:马来酸桂哌齐特对大鼠脑急性缺血再灌注损伤具有一定的保护作用。     

动脉移植BMSCs对脊髓缺血再灌注损伤大鼠脊髓细胞凋亡和caspase-9基因的影响

目的 探讨肾下腹主动脉移植骨髓间充质干细胞(BMSCs)对缺血再灌注损伤脊髓细胞凋亡、caspase-9表达及功能恢复的影响.方法 将大鼠随机分为假手术组、缺血再灌注组、移植组,每组8只.假手术组仅行手术操作;缺血再灌注组阻断肾下腹主动脉120 min后开放,恢复脊髓再灌注5 min后经动脉留置管推注1 mL培养基;移植组恢复再灌注5 min后推注100万BMSCs悬液1 mL.术后1、3和7d对大鼠进行BBB评分;用RT-PCR、Western blot 检测术后7d大鼠缺血节段脊髓内caspase-9基因和蛋白表达,TUNEL观察细胞凋亡.结果 缺血再灌注组和移植组大鼠BBB评分于术后1、3和7d均显著低于假手术组(P＜0.01),移植组术后3、7 d BBB评分高于缺血再灌注组(P＜0.01);移植组和缺血再灌注组损伤脊髓caspase-9 mRNA和蛋白表达水平较假手术组增加(P＜0.01),缺血再灌注组增加更为显著(P＜0.01).缺血再灌注组和移植组损伤脊髓内出现大量凋亡细胞,而移植组凋亡细胞数少于缺血再灌注组(P＜0.01).结论 肾下腹主动脉移植BMSCs可通过抑制缺血再灌注损伤脊髓caspase-9表达,减轻脊髓局部细胞凋亡,改善其神经功能恢复.     

大鼠局灶性脑缺血再灌注后bcl-2、bax表达和细胞凋亡

目的观察大鼠大脑中动脉重度栓塞后再灌注动物的脑细胞凋亡及其相关调控基因bcl-2和bax阳性蛋白质表达的变化;方法采用插线法制作大鼠大脑中动脉栓塞后再灌注模型,并观察脑缺血/再注不同时点大鼠脑细胞凋亡(TUMEL法)、凋亡相关调控基因bcl-2、bax(S-P免疫组化法)的阳性表达和脑组织含水量(Hallenbeck法)、脑梗塞体积(Nedergaard法)的变化.结果大鼠大脑中动脉栓塞3h、栓塞3h/再灌注24、48h时,细胞凋亡逐步加重,损伤加重,bcl-2、bax表达增强.     

糖尿病高血糖脑缺血再灌注梗死区周围微小血管病理变化

目的:探讨糖尿病高血糖状态下脑缺血再灌注损伤导致梗死灶周围微小血管的病理变化。方法:采用链脲佐菌素(STZ)诱导I型糖尿病高血糖大鼠模型,糖尿病高血糖脑缺血再灌注组(DM组)和正常血糖脑缺血再灌注组(NM组)通过线栓法制备大脑中动脉阻塞(MCAO)再灌注模型。通过HE和免疫组织化学方法,观察大脑中动脉阻塞30 min再灌注1,3,7,14 d后,各组梗死区周围微小血管形态、数量的变化及血管内皮细胞生长因子(VEGF)表达。结果:在MCAO 30 min,再灌注1 d,NM组梗死周边区域可见明显的神经元肿胀、脑水肿,再灌注7 d和14 d,基本恢复正常;DM组神经元固缩,脑水肿程度明显重于NM组,再灌注14 d仍可见脑水肿。在MCAO 30 min,再灌注3 d,缺血灶周围新生血管数量增多,表现为管腔形态不规则,内皮细胞数目增多,部分血管呈细条索状;再灌注7 d后,NM组血管基本恢复正常形态,DM组少部分微血管管腔狭窄。CD31标记血管计数可见,在MCAO 30 min,再灌注1 d,NM组和DM组梗死区周边微血管数量明显于少sham组(P0.05);再灌注3 d和14 d,DM组微血管数量明显多于NM组(P0.05);再灌注7 d,DM组微血管数量与NM组无显著差异。VEGF免疫组化可见,在MCAO 30 min,再灌注1,3,7,14 d,DM组梗死周边区微血管内皮细胞VEGF表达均明显高于NM组(P0.05)。结论:糖尿病高血糖可导致局灶性脑缺血梗死区周围微血管数量增加、内皮细胞肿胀、血管腔狭窄,加重脑缺血再灌注损伤。     

三七总皂苷对大鼠脑缺血再灌注损伤血清IL-8的影响

目的 :研究三七总皂苷对脑缺血再灌注损伤血清IL - 8的影响。方法 :线栓法制备大鼠大脑中动脉阻断 (middlecerebralarteryocclusion ,MCAO)局灶性脑缺血模型 ,缺血 2h ,再灌注 3h ,放免法测定血清IL - 8的含量。结果 :5 0mg/kg-1ip ,qd× 7d能降低大鼠脑缺血再灌注后血清IL - 8的含量。结论 :三七总皂苷通过降低大脑缺血再灌注后血清IL - 8的产生和释放 ,对脑缺血再灌注损伤有保护作用。     

不同序列间隔高频重复经颅磁刺激对运动区功率谱密度的影响

高频重复经颅磁刺激(rTMS)范式中序列间隔(ITI)参数对神经生理作用的影响尚未被充分研究。探讨不同ITI 高频rTMS刺激初级运动皮层对双侧运动区神经活动能量的影响。11名健康受试者参与ITI分别为25、50、100 s的真10 Hz rTMS及伪10 Hz rTMS,序列时长为5 s。在每次rTMS前后采集180 s闭目静息态脑电信号,分析rTMS前后双侧运动区总频段及delta、theta、alpha、beta、gamma1、gamma2各频段功率谱密度和其偏侧指数的变化。结果表明,25 s ITI rTMS对刺激侧运动区各频段功率谱密度均没有显著影响(P>0.05);50 s ITI rTMS使刺激侧theta和beta频段功率谱密度显著增加(P<0.05,theta频段刺激前后(11.42±1.01)dB vs(12.19±1.10)dB),beta频段刺激前后(10.71±0.99)dB vs(11.20±0.88)dB);同时使gamma2频段功率谱密度显著降低(P<0.05,刺激前后(4.94±0.97)dB vs(3.35±0.61)dB);100 s ITI rTMS使刺激侧theta、alpha和beta频段功率谱密度显著增加(P<0.05,theta频段刺激前后(11.29±1.00)dB vs(12.17±1.10)dB,alpha频段刺激前后(16.17±1.20)dB vs(17.74±1.20)dB,beta频段刺激前后(10.55±0.88)dB vs(11.26±0.90)dB)。rTMS诱发刺激对侧运动区各频段功率谱的变化与刺激侧运动区的变化基本相同。在实验中,rTMS均没有改变双侧运动区功率谱密度的偏侧指数(P>0.05)。研究结果表明,高频rTMS范式设置的ITI不同,对双侧运动区脑活动的影响不同,提示制定高频rTMS范式时,需慎重考虑ITI的设置。     

Serotonin transporter deficiency protects mice from mechanical allodynia and heat hyperalgesia in vincristine neuropathy

Repetitive transcranial magnetic stimulation (rTMS) is a standard tool in neuroscience research and therapy. Here we study one rTMS property that has not received adequate attention, the interaction of subthreshold intensity stimulation and low frequencies. We applied 1 Hz rTMS over the motor cortex at three intensities, 40%, 80% and 100% of the resting motor threshold (rMT), and measured cortical excitability before and after the stimulation sessions. When comparing motor evoked potential (MEP) measured from the abductor pollicis brevis (APB) muscle before and after rTMS stimulation, we found that low intensity (40% MT) stimulation significantly decreased MEP magnitude, some smaller (non-significant) inhibition was found for the 80% MT intensity and increased MEP was found for the high intensity (100% MT) stimulation. Our results indicate that when explaining the input-output relationship of motor cortex induced activation as an intensity-dependent function, there might be a need to split it into separate functions associated with separate processes mediated by different cell types such as interneurons, pyramidal neurons and others.     

The influence of low-frequency rTMS on EEG of rats

This study aimed to determine the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on electroencephalograms (EEGs) of rats. Fifteen Sprague-Dawley rats were subject to 100 pulses of 0.5 Hz rTMS, or sham stimulation. EEGs were recorded before stimulation and within 1 min after rTMS or sham stimulation. Estimates of the EEG correlation dimension (D(2)) and power spectra were calculated. Results show that the D(2) reduced significantly after low-frequency rTMS, but not after sham stimulation. Mean absolute power (MAP) of the gamma band and relative power (RP) of the beta and gamma bands reduce markedly after low-frequency rTMS, but there are no changes with sham stimulation. These results indicate that low-frequency rTMS could affect cortical activities significantly, but effects were markedly different from those of high-frequency rTMS.     

低频经颅磁刺激后脑电相关维数变化的分析

研究了低频经颅磁刺激(rTMS)对大鼠脑电相关维数的影响.实验对八只Sprague-Dawley大鼠进行频率为0.5Hz,100个脉冲的阈上经颅磁刺激,采集刺激前后大鼠的脑电信号进行分析.脑电数据经替代数据方法验证,具有非线性性质.计算刺激前后脑电的相关维数,发现刺激后大鼠脑电相关维数比刺激前有显著性降低,说明脑电的复杂度降低,该结果支持了低频经颅磁刺激对大脑有一定抑制作用的结论.     

Low frequency transcranial magnetic stimulation on the posterior parietal cortex induces visuotopically specific neglect-like syndrome

The visuo-parietal (VP) region of the cerebral cortex is critically involved in the generation of orienting responses towards visual stimuli. In this study we use repetitive transcranial magnetic stimulation (rTMS) to unilaterally and non-invasively deactivate the VP cortex during a simple spatial visual detection task tested in real space. Adult cats were intensively trained over 4 months on a task requiring them to detect and orient to a peripheral punctuate static LED presented at a peripheral location between 0° and 90°, to the right or left of a 0° fixation target. In 16 different interleaved sessions, real or sham low frequency (1 Hz) rTMS was unilaterally applied during 20 min (1,200 pulses) to the VP cortex. The percentage of mistakes detecting and orienting to contralateral visual targets increased significantly during the 15–20 min immediately following real but not sham rTMS. Behavioral deficits were most marked in peripheral eccentricities, whereas more central locations were largely unaffected. Performance returned to baseline (pre-TMS) levels when animals were tested 45 min later and remained in pre-TMS levels 24 h after the end of the stimulation. Our results confirm that the VP cortex of the cat is critical for successful detection and orienting to visual stimuli presented in the corresponding contralateral visual field. In addition, we show that rTMS disrupts a robust behavioral task known to depend on VP cortex and does so for the far periphery of the visual field, but not for more central targets.Prof. Payne passed away May 2004. This article is submitted in his memory.     

重复经颅磁刺激治疗精神分裂症阴性症状的疗效分析

目的：探讨重复经颅磁刺激（rTMS）治疗精神分裂症阴性症状的效果和安全性。方法：25例以阴性症状为主的精神分裂症患者随机分为真刺激及伪刺激治疗组，共接受20次rTMS治疗。治疗开始及疗程结束时使用阳性和阴性症状量表（PANSS）及Anderson的阴性症状量表（SANS）评定疗效。结果：治疗结束后，真刺激组SANS总分减分率为52．38±14．48％，伪刺激组SANS总分减分率为1．84±3．34％，两组阴性症状的改善状况差异明显（P〈0．01）。治疗前后，rTMS真刺激组的PANSS总分和N分减分率也明显高于伪刺激组（P〈0．01）。结论：抗精神病药物治疗合并rTMS治疗对精神分裂症阴性症状有效。     

青年难治性抑郁症患者重复经颅磁刺激治疗研究

目的:探讨高频重复经颅磁刺激(rTMS)对单相难治性抑郁症的治疗价值和安全性。方法:36例青年难治性抑郁症患者随机分为真刺激组及药物治疗组,共接受20次rTMS治疗。治疗开始及疗程结束时使用汉密尔顿抑郁量表(HAMD)、贝克抑郁自评量表(BDI)、大体功能评定量表(GAF)及匹茨堡睡眠质量指数量表(PSQI)评定疗效。结果:治疗结束后,磁刺激组有效12例,其中痊愈4例,有效率为63.2%。药物组有效2例,有效率11.8%。卡方值为14,P=0.000。rTMS组治疗后,患者HAMD评分从治疗前(24.68±3.01)分降低到(13.53±5.19),药物组HAMD评分治疗前(24.47±2.62),治疗后(20.88±4.30)。两组治疗后HAMD评分有显著性差异(P0.01)。治疗后,rTMS组的BDI、GAF及PSQI评分也明显低于单纯药物组,两组症状改善状况差异明显(P0.05)。结论:重复经颅磁刺激合并抗抑郁药物治疗难治性抑郁症安全有效。     

重复经颅磁刺激对失眠症患者睡眠的影响

目的观察重复经颅磁刺激(rTMS)对失眠症患者的临床疗效。方法将60例失眠症患者分为rTMS组和对照组,各30例。对照组每晚口服艾司唑仑1~2mg,rTMS组行rTMS治疗,均治疗14d,予多导睡眠检测仪检测治疗前后两组患者睡眠进程和睡眠结构的变化,治疗前后行匹茨堡睡眠质量指数量表(PSQI)评定,比较两组疗效。结果两组PSQI评分较治疗前均降低,差异有统计学意义(t=6.94,6.19;P0.05),治疗后两组PSQI评分差异无统计学意义。治疗后两组患者的睡眠时间、睡眠潜伏期、觉醒时间、睡眠效率等较治疗前均改善,差异有统计学意义(t=2.61~7.14,P均0.05);治疗后rTMS组较对照组相比,S2较短,S3和REMS较多,差异有统计学意义(t=7.09,6.32,4.61;P均0.05)。结论 rTMS能改善失眠症患者的睡眠质量。     

Stimulus waveform influences the efficacy of repetitive transcranial magnetic stimulation

BACKGROUND: Optimising stimulus parameters is important in maximising the efficacy of repetitive transcranial magnetic stimulation (rTMS) in treatment applications. RTMS over motor cortex has been reported as more effective in producing corticospinal inhibition when a monophasic rather than a biphasic stimulus waveform is used. However, non-optimal coil orientation and high intensities of monophasic rTMS may have influenced previous results. METHODS: In eight healthy subjects, we measured motor evoked potentials (MEPs) in a hand muscle after monophasic and biphasic rTMS (1 Hz for 15 min) over the motor cortex with the coil always in the optimal orientation. MEPs were evoked by both monophasic and biphasic stimuli. RESULTS: MEPs were initially significantly reduced after monophasic but not biphasic rTMS. However, a late reduction was seen after biphasic rTMS. LIMITATIONS: These motor cortical findings may not be directly applicable to prefrontal rTMS. CONCLUSIONS: This study confirms that low frequency rTMS with monophasic pulses produces more corticospinal inhibition than with biphasic pulses, even when the direction of current and intensity are as well-matched as possible.     

Effects of Repetitive Transcranial Magnetic Stimulation on Behavioral Recovery during Early Stage of Traumatic Brain Injury in Rats

Repetitive transcranial magnetic stimulation (rTMS) is a promising technique that modulates neural networks. However, there were few studies evaluating the effects of rTMS in traumatic brain injury (TBI). Herein, we assessed the effectiveness of rTMS on behavioral recovery and metabolic changes using brain magnetic resonance spectroscopy (MRS) in a rat model of TBI. We also evaluated the safety of rTMS by measuring brain swelling with brain magnetic resonance imaging (MRI). Twenty male Sprague-Dawley rats underwent lateral fluid percussion and were randomly assigned to the sham (n=10) or the rTMS (n=10) group. rTMS was applied on the fourth day after TBI and consisted of 10 daily sessions for 2 weeks with 10 Hz frequency (total pulses=3,000). Although the rTMS group showed an anti-apoptotic effect around the peri-lesional area, functional improvements were not significantly different between the two groups. Additionally, rTMS did not modulate brain metabolites in MRS, nor was there any change of brain lesion or edema after magnetic stimulation. These data suggest that rTMS did not have beneficial effects on motor recovery during early stages of TBI, although an anti-apoptosis was observed in the peri-lesional area.