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1.
深部脑刺激(deep brain stimulation,DBS)在许多神经系统疾病的临床治疗上都展现出良好的应用前景,然而,其作用机制尚不明确.常规DBS采用高频刺激(high frequency stimulation,HFS)的脉冲序列,这种窄脉冲最容易激活神经元结构中的轴突部分,通过轴突的投射,将HFS的作用传播至下游神经元.因此,为了探讨DBS的作用机制,并鉴于海马脑区是治疗癫痫和痴呆症等疾病的重要靶点,我们研究了海马区轴突HFS对于下游神经元的作用.对麻醉大鼠的海马CA1区传入神经通路Schaffer侧支施加1 min的100 Hz高频刺激,记录并提取下游CA1区锥体神经元和中间神经元的单元锋电位.计算锋电位的发放率,以及它们与刺激脉冲之间的锁相值(phase-locking value,PLV)和潜伏期,以定量分析HFS期间神经元动作电位发放的变化趋势.结果显示,在传入轴突上施加HFS时,初期会诱发下游神经元群体同步产生动作电位(即群峰电位).在HFS后期(群峰电位消失之后),两类神经元的单元锋电位发放仍然持续,并且发放率较稳定.但是,锋电位与刺激脉冲之间的锁相性逐渐减弱、潜伏期逐渐延长.而且,与中间神经元相比较,锥体神经元锋电位的锁相性更弱、潜伏期更长.这些结果表明,持续的轴突HFS可以诱导下游神经元产生非同步的活动,高频脉冲刺激引起的不完全轴突传导阻滞可能是导致该现象产生的主要原因.本文的研究为揭示脑刺激的作用机制提供了重要信息.  相似文献   

2.
深部脑刺激(deep brain stimulation,DBS)已成为治疗帕金森病等运动障碍疾病的常规方法之一,并且在许多其他神经和精神疾病的治疗中也具有良好的应用前景.但是,目前常规DBS采用单通道恒定脉冲间隔的高频刺激(high frequency stimulation,HFS),刺激模式缺少多样化,限制了DBS在临床上的推广应用.为了开发更多DBS刺激模式,用于改善疗效、拓展应用范围、并节省刺激器的电能,近年来研究人员基于去同步调控机制,在脉冲序列的时间模式和空间排布两方面开发了DBS新模式.主要包括:变频序列(包括规则变频和随机变频)、不同空间位点上的多通道异步刺激以及变频和多通道两者的结合.这些新刺激模式能够提高DBS的临床疗效、降低刺激能耗,在帕金森病以及癫痫、强迫症和微意识障碍等其他脑疾病的治疗中都展现了良好的应用前景.更值得关注的是,多通道异步刺激不仅在刺激期间具有更好的即时疗效,而且刺激结束后还能长时间保持疗效,具有刺激后效应.这个特性突破了常规DBS主要为即时效应的局限性,展现了DBS新前景.本文在概述常规DBS模式及其去同步调控机制的基础上,综述变频脉冲刺激和多通道刺激等新型DBS模式,可以为促进DBS的发展提供有价值的信息.  相似文献   

3.
目的 深部脑刺激(deep brain stimulation,DBS)利用持续的电脉冲高频刺激(high-frequency stimulation,HFS)调控神经元的活动,可望用于治疗更多脑疾病。为了深入了解HFS的作用机制,促进DBS的发展,本文研究轴突HFS在引起轴突阻滞期间神经元胞体的改变。方法 在麻醉大鼠海马CA1区的锥体神经元轴突上施加脉冲频率为100 Hz的1 min逆向高频刺激(antidromic high-frequency stimulation,A-HFS)。为了研究胞体的响应,利用线性垂直排列的多通道微电极阵列,记录刺激位点上游CA1区锥体神经元胞体附近各结构分层上的诱发电位,包括A-HFS脉冲诱发的逆向群峰电位(antidromic population spike,APS)以及A-HFS期间施加的顺向测试脉冲诱发的顺向群峰电位(orthodromic population spike,OPS),并计算诱发电位的电流源密度(current-source density,CSD),用于分析A-HFS期间锥体神经元胞体附近动作电位的生成和传导。结果 锥体神经...  相似文献   

4.
深部脑刺激器(deep brain stimulator),也经常被称为脑起搏器,是可植入人体设备,并连续不断地传送刺激脉冲到深部脑组织的特定区域,即所谓的深部脑刺激(deep brain stimulation,DBS).迄今为止,深部脑刺激是治疗严重顽固抗药性运动障碍疾病(如帕金森病,原发性震颤及肌张力异常等)的最有效的外科治疗手段之一.此外,广大的科研工作者也不断地探索应用DBS治疗其他神经及精神异常(如,癫痫和强迫症)的新的临床应用.尽管应用DBS治疗运动障碍非常有效,并也迅速被探索性地应用到其他神经障碍治疗中,但其作用机制仍然不是十分清楚,成为学者们争论的热点.DBS治疗效果的作用机制通常有两种基本的观点:高频刺激抑制学说及高频刺激兴奋学说.基于最近发表的关于中枢神经系统内的高频刺激效应的资料、数据及相关评论,两种机制共存并发挥作用的DBS作用假说被提出,认为DBS通过施加高频刺激干扰并控制了核团病理性紊乱随机活动,同时施加兴奋性刺激到其他基底节的网络,以实现对帕金森病的治疗.  相似文献   

5.
通常采用恒定电脉冲间隔的高频刺激(high-frequency stimulation,HFS),进行深部脑刺激治疗帕金森氏症等运动障碍疾病.为了开发适用于不同脑疾病治疗的新刺激模式,近年来脉冲间隔(inter-pulse-interval,IPI)变化的变频刺激模式受到关注.已有研究表明,即使具有相同的平均电脉冲频率,变频刺激与恒频刺激的治疗效果也不同.我们推测,变频刺激的短小IPI变化就足以改变HFS对于神经元的作用.为了验证此推测,本文在大鼠海马CA1区锥体神经元的输入轴突纤维上交替施加恒频刺激(100或133 Hz,即IPI=10 ms或7.5 ms)和随机变频刺激(100~200 Hz,即IPI=5~10 ms,平均频率为133 Hz),记录并分析刺激下游神经元群体的诱发电位,用于定量评价神经元对于恒频和变频刺激的响应.实验结果表明,持续的恒频刺激使得神经元的响应从最初的同步发放形成的群峰电位(population spike,PS)转变为非同步的动作电位发放(即单元锋电位).但是,当刺激切换为变频模式时,却又可以诱发神经元群体同步产生动作电位,重新形成PS波.并且,变频刺激诱发的PS幅值和神经元发放的同步程度可达基线的单脉冲刺激诱发波的水平.但是,PS的发生率只有脉冲刺激频率的7%左右,表明在持续的变频刺激时,多个脉冲累积的作用才能诱发这种同步的神经元发放.而且PS的出现与前导IPI的长度之间存在一定关系.神经元的轴突和突触等结构对于高频刺激的非线性响应可能是变频刺激诱发同步活动的原因.这些结果表明,变频刺激序列中短小的间隔变化可以产生与恒定间隔不同的调控作用.本文的结果对于揭示脑刺激的作用机制,促进新型刺激模式的开发及其在不同类型脑疾病治疗中的应用具有重要意义.  相似文献   

6.
为了正确检测和研究高频电刺激(high frequencystimulation,HFS)期间神经元的动作电位发放活动,进而深入揭示深部脑刺激治疗神经系统疾病的机制,本课题研究HFS期间锋电位波形的变化.在麻醉大鼠海马CA1区的输入神经通路Schaffer侧支上,施加1~2 min时长的100或者200 Hz顺向高频刺激(orthodromic-HFS,O-HFS),利用微电极阵列采集刺激下游神经元的多通道锋电位信号,并获得由O-HFS经过单突触传导激活的中间神经元的单元锋电位波形及其特征参数.结果表明,O-HFS使得锋电位的幅值明显减小而半高宽明显增加,以基线记录为基准计算百分比值,O-HFS期间锋电位的降支幅值和升支幅值分别可减小20%和40%左右,半高宽则增加10%以上.并且,在大量神经元同时产生动作电位期间,或者在比200 Hz具有更大兴奋作用的100 Hz刺激期间,锋电位波形的改变更多,幅值的减小可达50%,宽度的增加可达20%.可以推测,高频电刺激对于神经元的兴奋作用可能升高细胞膜电位,从而改变细胞膜离子通道的活动特性,导致动作电位波形的改变.这些结果支持深部脑刺激具有兴奋性调节作用的假说,对于正确分析高频电刺激期间神经元锋电位活动具有指导意义,也为进一步研究深部脑刺激(DBS)治疗脑神经系统疾病的机制提供了重要线索.  相似文献   

7.
闭环刺激是深部脑刺激(deep brain stimulation,DBS)的重要发展方向之一,有望用于治疗多种脑神经系统疾病.与常规开环的长时间持续刺激不同,闭环刺激通常采用短促的高频脉冲序列.而神经元对于高频刺激的响应存在暂态过程,在初期的短时间内会发生很大变化,从而影响闭环刺激的作用.为了研究这种暂态过程,在大鼠海马CA1区传出轴突纤维(alveus)上施加不同频率的恒频以及随机变频的逆向高频刺激(antidromic high-frequency stimulation,A-HFS),并以逆向诱发的群峰电位(antidromically-evoked population spike,APS)的幅值作为指标来考察神经元群体的响应.研究结果表明,100、133和200 Hz的恒频A-HFS初期,APS迅速衰减,脉冲频率越高,APS衰减越快.平均不到1 s时间内APS的幅值就会下降一半以上,100 Hz时的平均半衰期为~0.96 s,频率增加1倍至200 Hz时,平均半衰期缩短至~0.21 s.使用100~200 Hz范围内实时微调脉冲间隔的随机变频刺激,则可以显著延缓神经元响应的衰减速度,延长刺激作用的维持时间.这些结果可以为短促闭环刺激等DBS新模式的开发提供依据.  相似文献   

8.
在中枢神经系统中,脱髓鞘病变后的机体可以实现一定程度的再髓鞘修复,但尚不足以诱导功能恢复。越来越多的研究表明,神经元电活动作为一种轴突信号,调控着发育性成髓鞘过程并且能够启动及促进轴突再髓鞘。通过激活神经元电活动促进轴突再髓鞘修复的策略已经成为治疗相关疾病的潜在突破口,但该再髓鞘过程中涉及到的少突胶质谱系及星形胶质细胞的变化及机制仍不够清楚。该文拟主要围绕神经元电活动调控轴突再髓鞘的相关机制进行综述,为今后研究提供参考。  相似文献   

9.
脑刺激是神经科学研究的重要手段,传统的经颅磁刺激和经颅电刺激等脑刺激方法尽管能调控运动功能(包括减轻运动性障碍疾病的运动障碍、提高运动能力等),但存在空间分辨率低且无法刺激深部脑组织的局限性.近年来迅速发展的深部脑刺激(deep brain stimulation,DBS)、光遗传学、经颅超声刺激(transcranial ultrasound stimulation,TUS)、时间干涉(temporal interference,TI)等精准定位脑刺激方法,具有空间分辨率高、可聚焦深部脑组织等优点.本文综述了上述几种脑刺激方法的原理、特点,对运动功能调控的研究进展,以及面临的挑战和发展前景,从而为神经科学研究提供更好的研究工具,为临床实践提供更多的干预治疗手段.  相似文献   

10.
神经振荡是中枢神经系统中一种节律性神经活动模式,研究发现精神神经类疾病患者存在神经振荡异常。外源节律性刺激能够通过“夹带”效应以及可塑性变化机制有效调节异常的神经振荡,具有治疗精神神经类疾病的潜在可能性。目前,外源节律性脑刺激技术主要包括经颅交流电刺激、经颅时间相干刺激、节律性感觉刺激等方式。本文从外源节律性脑刺激技术原理以及目前不同技术在临床上治疗精神神经类疾病的刺激策略、研究进展以及治疗效果等角度展开综述,提出这一类调控技术可能成为未来临床治疗精神神经疾病症状的无创高效新型治疗方案,并对其未来的发展方向进行展望。  相似文献   

11.
A. E. LUGO 《Austral ecology》2008,33(4):368-398
Abstract Hurricanes have visible and invisible effects on forests. The visible effects are dramatic, noticeable over the short‐term and relatively well documented in the literature. Invisible effects are less understood as they require well‐focused research both in the short‐ and long‐term time scales. This review of the literature on hurricane effects focuses on the Neotropics and the temperate zone of North America. The material is organized according to a heuristic model that distinguishes between immediate effects (0 to 3 years), immediate responses (0 to 20 years), trajectories of responses (0 to 100 years) and long‐term legacies (>100 years). It is suggested that the ecological role of hurricanes involves six principal effects: 1. they change the ecological space available to organisms; 2. they set organisms in motion; 3. they increase the heterogeneity of the landscape and the variability in ecosystem processes; 4. they rejuvenate the landscape and its ecosystems and redirect succession; 5. they shape forest structure, influence their species composition and diversity and regulate their function; and 6. they induce evolutionary change through natural selection and ecological creativity through self‐organization. A new approach to hurricane research will study hurricanes at the same scale at which they operate (i.e., across latitudes and longitudes and over disturbed and undisturbed landscapes). This research will require networks of observation platforms located along expected hurricane paths to facilitate forest structure and functioning observations across gradients of hurricane frequency and intensity. This research will also require use of remote sensing and automated wireless technology, hardened to survive hurricane‐strength winds and floods to assure real time measurements of the characteristics of hurricanes and ecosystem responses. No progress will be forthcoming in the understanding of hurricane effects if we do not learn to quantify objectively the energy dissipation of hurricanes on the full grid of affected forests as the hurricane passes over a landscape.  相似文献   

12.
Karyotypes of 18 populations belonging to eight of the southernmost species of South American Crotalaria were examined. All had x  = 8, except C. incana which had x  = 7. Diploid, tetraploid and octoploid species were found. The octoploid is a new record and is the highest ploidy level detected so far in the genus. Species within the same ploidy level could be distinguished by quantitative karyotype parameters and by the size and position of the satellites. From an evolutionary point of view, our results support a decrease of the basic chromosome number by dysploidy. Polyploidy is one of the more important mechanisms of chromosome change, even though some structural rearrangements may explain variations of the karyotype formula. Gigas effects, due to polyploidy, were evident in the length of the stomatal guard cells and in pollen size, but were less clear in seed weight. Nucleotype effects, caused by the DNA quantity in a nucleus, were also evident for pollen and stomatal guard cell size and seed weight, although only in diploids with x  = 8 for the latter character. Chromosome data are further discussed in the light of the infrageneric systematic arrangement.  © 2006 The Linnean Society of London, Botanical Journal of the Linnean Society , 2006, 150 , 329–341.  相似文献   

13.
Summary Genetic factors controlling the differential expression of somatic embryogenesis and plant regeneration of maize from tissue culture were studied in two crosses. Inbred, hybrid, F2 and backcross generations developed from crossing maize inbred A188 with two commercially important inbred maize lines (B73 and Mo17) demonstrated genetic and environmental effects on somatic embryogenesis and plant regeneration when immature zygotic embryos were cultured on MS medium. Additive gene effects were more important in both crosses than dominant gene effects for precent somatic embryogenesis and percent or number of plants regenerated per embryo when generation means were analyzed. In backcross generations of each cross, cytoplasmic, maternal and/or paternal effects were significant for frequency of somatic embryos three weeks after culture as well as frequency, or number of plants regenerated per embryo, nine weeks after culture. Analysis of genetic variances suggests at least one gene (or block of genes) controls the expression of the frequency of somatic embryogenesis in these crosses. Differences in somatic embryogenesis and plant regeneration between B73 and Mo17 are discussed. This is Journal Paper No. 11,435 of the Purdue University Agricultural Experiment Station.  相似文献   

14.
小干扰RNAs(small interfere RNAs,siRNAs)能够特异性沉默靶基因,现已广泛应用于阐明基因功能,鉴定药物靶点,开发比目前更有效的治疗药物。然而siRNA脱靶效应(off-target effects,OTEs)导致基因沉默实验中表型效应解释复杂化,引起siRNA治疗毒副作用。与siRNA有关的脱靶效应有microRNA样脱靶效应、免疫刺激、RNAi元件饱和三种类型。综述了siRNA脱靶效应类型及减轻脱靶效应的方法,以增强该技术的实用性。  相似文献   

15.
Abstract.— Phenotype is often viewed as a product of genes and the environment in which these genes are expressed. However, numerous studies have shown that environment can cause lasting changes in phenotype that can be passed from one generation to the next, much as genes are transmitted. In clonally propagated organisms, persistence of environmental effects has been observed in a range of plant and animal species, but has rarely been the object of study. We measured the persistence and magnitude of environmental effects on phenotype over three clonal generations in the arctic sedge Eriophorum vaginatum . We found that the environment in which tillers developed had large effects on their later performance (parental effects) and that these effects were in part independent of the size of tillers. The magnitude and persistence of environmental effects did not differ between environmental treatments or among genotypes. However, after 52 weeks of growth and two rounds of clonal propagation, grandparental treatment effects were not significant. We describe methods that can be used in quantitative genetics studies of clonal organisms to reduce bias in estimates of genotypic and environmental variance and argue that the persistence of environmental effects in clonal plant material has ecological and evolutionary consequences similar to those described for maternal environmental effects in sexual organisms.  相似文献   

16.
17.
Aukema BH  Clayton MK  Raffa KF 《Oecologia》2004,139(3):418-426
Multiple predator species feeding on a common prey can lead to higher or lower predation than would be expected by simply combining their individual effects. Such emergent multiple predator effects may be especially prevalent if predators share feeding habitat. Despite the prevalence of endophagous insects, no studies have examined how multiple predators sharing an endophytic habitat affect prey or predator reproduction. We investigated density-dependent predation of Thanasimus dubius (Coleoptera: Cleridae) and Platysoma cylindrica (Coleoptera: Histeridae) on a bark beetle prey, Ips pini (Coleoptera: Scolytidae), in a laboratory assay. I. pini utilize aggregation pheromones to group-colonize and reproduce within the stems of conifers. T. dubius and P. cylindrica exploit these aggregation pheromones to arrive simultaneously with the herbivore. Adult T. dubius prey exophytically, while P. cylindrica adults enter and prey within the bark beetle galleries. Larvae of both predators prey endophytically. We used a multiple regression analysis, which avoids confounding predator composition with density, to examine the effects of varying predator densities alone and in combination on herbivore establishment, herbivore reproduction, and predator reproduction. Predators reduced colonization success by both sexes, and decreased I. pini reproduction on a per male and per female basis. The combined effects of these predators did not enhance or reduce prey establishment or reproduction in unexpected manners, and these predators were entirely substitutable. The herbivores net replacement rate was never reduced significantly below one at prey and predator densities emulating field conditions. Similar numbers of each predator species emerged from the logs, but predator reproduction suffered from high intraspecific interference. The net replacement rate of P. cylindrica was not affected by conspecifics or T. dubius. In contrast, the net replacement rate of T. dubius decreased with the presence of conspecifics or P. cylindrica. Combinations of both predators led to an emergent effect, a slightly increased net replacement rate of T. dubius. This may have been due to predation by larval T. dubius on pupal P. cylindrica, as P. cylindrica develops more rapidly than T. dubius within this shared habitat.  相似文献   

18.
For several decades, the prevailing paradigm for modeling the effects of ionizing radiation (IR) on living systems was the target model with its inherent assumptions--that only those cells in the radiation path whose molecules sustained collisions with high energy particles and rays were damaged, that the damage was proportional to the energy absorbed by each cell and to the number of cells absorbing energy, and that all cells had identical sensitivities to radiation. However, evidence has accumulated that cells exhibit phenomena at low radiation exposures that appear to contradict at least one of these assumptions. Some of these phenomena currently under active study include low-dose hypersensitivity (HRS), increased radiation radioresistance (IRR), the adaptive response (AR), the bystander effect (BE), and death-inducing factor (DIE). These effects may interact to give rise to other phenomena such as hormesis, in which small amounts of otherwise toxic agent appear to be beneficial. Elucidating the cellular and molecular bases for these phenomena will lead to greater understanding of the relationships of these processes, including hormesis, to human health.  相似文献   

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铅对生物体具有多方面的毒性,可导致智力低下、造血机能障碍、高血压、肾病等,其毒性机理还在探索阶段。本文主要介绍了铅对各个系统如神经系统、心血管系统、泌尿系统、生殖系统以及个体发育的毒性效应。  相似文献   

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