丘脑前核在三叉神经电刺激减轻癫痫发作和海马神经元损伤中的作用

 目的：探讨丘脑前核在三叉神经电刺激（TNS）减轻癫痫发作和海马神经元损伤中的作用。方法：大鼠经腹腔注射匹罗卡品建立慢性癫痫模型,模型大鼠分别给予假刺激、三叉神经电刺激和立体定向毁损丘脑前核预处理后三叉神经电刺激1月,再次诱导癫痫发作,观察大鼠的癫痫行为表现,并通过TUNEL、Fluoro-Jade B (FJB)染色和Nissl染色观察大鼠海马CA1区神经元的凋亡、变性及脱失情况。结果：与未经毁损丘脑前核的TNS处理大鼠相比,毁损丘脑前核后的TNS处理大鼠癫痫发作的级别分数及持续时间明显增加（P<0.05）,且毁损丘脑前核后的TNS处理大鼠癫痫发作后海马CA1区TUNEL、FJB阳性细胞及细胞的脱失较TNS组显著增加（P<0.01）。结论：毁损丘脑前核后,TNS减轻癫痫发作及海马神经元损伤的作用被显著降低,表明丘脑前核在TNS抗癫痫中发挥一定的作用;潜在机制可能是TNS通过丘脑前核慢性激活丘脑与大脑皮层的纤维联系,使海马神经元兴奋性易感性改变。     

基于匹配追踪的癫痫脑电信号的时频分析

目的 鉴于匹配追踪算法具有良好的参数化描述特性,应用匹配追踪算法研究癫痫脑电的时频分布特征.方法 通过仿真算例,将匹配追踪算法与短时傅里叶变换、Wigner-Ville分布结果进行比较,验证该方法的频率分辨率高及参数化表征的优越性;应用上述3种方法对癫痫脑电和正常脑电进行时频分析,研究癫痫异常放电在时频平面的表现.结果 仿真结果表明基于匹配追踪算法能得到较好的时频分布;对癫痫脑电和正常脑电进行时频分析,癫痫脑电和正常脑电在时频平面上存在明显的差异.结论 基于匹配追踪的时频分析方法,能够更好地揭示脑电类非平稳信号的特征.     

颈部迷走神经干刺激对癫痫大鼠脑内Fos样表达的影响

目的 研究颈部迷走神经干刺激（VNS）抑制癫痫发作上传通路过程中的关键核团及相关脑区。方法 利用红藻氨酸（KA）诱发大鼠复杂部分性癫痫发作。并结合Fos免疫组织化学方法观察左颈部迷走神经干电刺激后全脑及延髓内Fos的分布及电刺激的影响。结果 VNS后脑干双侧孤束核、蓝斑、臂旁核、中脑导水管周围灰质有很强的特异性Fos表达，外侧缰核、丘脑室旁核、菱形核、下丘脑室旁核、杏仁中央核、终纹床核、隔外侧核、梨状皮质等脑区亦可见Fos阳性细胞。预先给予电刺激后海马、齿状回、额、顶、颞皮质区域Fos表达明显受到抑制。结论 VNS后Fos阳性的脑区及核团可能是电刺激发挥抑痫作用的关键部位，其神经元活性的改变或递质调节可能间接或直接影响大脑皮质的功能。     

迷走神经刺激对戊四氮致痫大鼠丘脑网状核NMDAR1 mRNA和GABAARα1 mRNA的影响

为探讨迷走神经刺激（Vagus nerve stimulation,VNS)抗癫痫的作用机制。应用原位杂交组织化学及图像分析方法研究戊四氮（Pentylenetetrazol,PTZ)致痫大鼠丘脑网状核谷氨酸受体NMDAR1mRNA和γ-氨基丁酸A受体（GABAAR）α1亚单位mRNA的变化。结果显示，PTZ致痫组大鼠丘脑网状核NMDAR1mRNA表达明显高于正常对照组，而VNS抗癫痫组明显低于PTZ致癫痫组，与之相反，PTZ致癫痫组GABAARα1mRNA的表达明显低于正常对照组，VNS抗癫痫组明显高于PTZ致癫痫组，上述结果表明，VNS可能通过抑制丘脑网状核兴奋的神经递质受体NM-DAR的活动和增强抑制性神经递质受体γ-氨基丁酸受体GABAAR的活动，降低大脑皮层的兴奋性，抑制癫痫的发生和发展。     

丘脑网状核介导睡眠纺锤波形成的机制研究进展

睡眠纺锤波主要存在于非快速动眼(NREM)睡眠的第二阶段，是NREM睡眠特有的脑电相位特征。睡眠纺锤波对睡眠稳态、认知及学习记忆等至关重要。研究表明，睡眠纺锤波的形成是由于丘脑网状核(TRN)抑制性神经元与丘脑-皮层环路的连接神经元发生电位同步相应，从而导致皮层神经元突触电位以纺锤体样频率振荡(11～16 Hz)。其中，TRN核团神经元放电模式的变化被认为是睡眠纺锤波形成的基础。然而，TRN核团在纺锤波形成中的调控机制仍不清楚。本篇综述将回顾TRN核团如何通过丘脑-皮层环路影响睡眠纺锤波形成的研究进展。     

自回归模型和隐马尔可夫模型在癫痫脑电识别中的应用

目的研究自回归(autoregressive model,AR)模型和隐马尔可夫模型(hidden Markov model,HMM)在癫痫脑电(electroencephalogram,EEG)识别中的应用,以期减轻医生工作量,减少人工识别主观因素的影响。方法使用基于联合信息准则(combined information criterion,CIC)的最佳阶数AR模型对脑电信号进行特征提取,连续密度隐马尔可夫模型(continuous density hidden Markov model,CD-HMM)作为正常脑电和癫痫脑电的分类工具,对南京军区总医院的临床脑电数据(8组采样频率为512 Hz的16导正常、癫痫脑电信号)进行分析和识别。实验时对每一例样本选取T3、T4、FP1、FP2、C3、C4六个导联的数据。使用训练集中的15段样本进行HMM建模,剩下35段用作测试。结果癫痫脑电的识别率可达90%。结论 AR模型结合HMM建模的方法对正常脑电信号和癫痫脑电的识别率较高,在脑-机接口设备的开发中有一定的应用前景。     

实验性大鼠癫痫模型异常脑电波及及物理特征

本文研究了局灶性及全身性青霉Ｇ钠诱发大鼠癫痫模型异常脑电波及其物理参量特征性改变特点。采用１７０Ｕ青霉素Ｇ钠置于大鼠硬脑膜外表面诱发癫痫发放是制成局灶性癫痫模型，腹腔注射１，２００，０００Ｕ青霉素诱发大鼠急性全身癫痫模型。癫痫放电的型式有：棘波、尖波、棘慢波综合、高幅失律等，施加处理因素后可以经起癫痫放电频率、振幅、左右对称性、正、负波相们比例以及癫痫放电型式的改变。     

实验性大鼠癫痫模型异常脑电波及物理特征

本文研究了局灶性及全身性青霉素Ｇ钠诱发大鼠癫痫模型异常脑电波及其物理参量特征性改变特点。采用１７０Ｕ青霉素Ｇ钠置于大鼠硬脑膜外表面诱发癫痫放电制成局灶性癫痫模型，腹腔注射１，２００，０００Ｕ青霉素诱发大鼠急性全身性癫痫模型。癫痫放电的主要型式有：棘波、尖波、棘（尖）慢波综合、高幅失律等。施加处理因素后可以引起癫痫放电频率、振幅、左右对称性、正、负波相位比例以及癫痫放电型式的改变。     

基于通用赤池信息量准则改进维纳-格兰杰因果索引算法的颅内脑电效应连通性研究

本文的目标是处理并分析使用深度电极在难治性癫痫患者癫痫发作期间其大脑皮层中记录到的癫痫脑电信号间的大脑效应连通性。维纳-格兰杰因果索引算法是一种众所周知的检测脑电信号间大脑效应连通性的有效方法。它是一种基于线性自回归模型的方法,而模型参数估计问题在其用于脑电因果效应连通性研究中的计算准确性与鲁棒性方面起着至关重要的作用。本文针对这一问题,使用了我们提出的改进的赤池信息量准则来估计算法中自回归模型的模型阶数,以提高维纳-格兰杰因果索引算法检测大脑效应连通性的性能。实验仿真结果表明:不管是在线性随机系统中还是在能生成模拟癫痫信号的生理模型中,该改进的维纳-格兰杰因果索引算法在检测脑效应连通性上都表现出良好的鲁棒性。     

大脑模型混沌特性的仿真实验

随着国内外对脑电非线性研究的发展,人们已经发现了脑电的混沌特性。我们在国外大量生物学实验研究的基础上,根据大脑皮层的生理和解剖性质,采用反馈这样一种系统结构,建立起大脑皮质层简化的生理模型。通过适当选择模型的参数,模拟了脑电的混沌行为,我们还连续调整了模型参数,证明了脑电的混沌是一种Rellc-Takens-NewhOuse混沌。另外,通过改变模型的参数,我们初步解释了病理条件下的脑电波形的神经机理。     

Neuronal Networks in West Syndrome as Revealed by Source Analysis and Renormalized Partial Directed Coherence

West syndrome is a severe epileptic encephalopathy of infancy with a poor developmental outcome. This syndrome is associated with the pathognomonic EEG feature of hypsarrhythmia. The aim of the study was to describe neuronal networks underlying hypsarrhythmia using the source analysis method (dynamic imaging of coherent sources or DICS) which represents an inverse solution algorithm in the frequency domain. In order to investigate the interaction within the detected network, a renormalized partial directed coherence (RPDC) method was also applied as a measure of the directionality of information flow between the source signals. Both DICS and RPDC were performed for EEG delta activity (1–4 Hz) in eight patients with West syndrome and in eight patients with partial epilepsies (control group). The brain area with the strongest power in the given frequency range was defined as the reference region. The coherence between this reference region and the entire brain was computed using DICS. After that, the RPDC was applied to the source signals estimated by DICS. The results of electrical source imaging were compared to results of a previous EEG-fMRI study which had been carried out using the same cohort of patients. As revealed by DICS, delta activity in hypsarrhythmia was associated with coherent sources in the occipital cortex (main source) as well as the parietal cortex, putamen, caudate nucleus and brainstem. In patients with partial epilepsies, delta activity could be attributed to sources in the occipital, parietal and sensory-motor cortex. In West syndrome, RPDC showed the strongest and most significant direction of ascending information flow from the brainstem towards the putamen and cerebral cortex. The neuronal network underlying hypsarrhythmia in this study resembles the network which was described in previous EEG-fMRI and PET studies with involvement of the brainstem, putamen and cortical regions in the generation of hypsarrhythmia. The RPDC suggests that brainstem could have a key role in the pathogenesis of West syndrome. This study supports the theory that hypsarrhythmia results from ascending brainstem pathways that project widely to basal ganglia and cerebral cortex.     

Cortical control of unilateral simple movement in healthy aging

Normal aging is associated with several modifications in the cerebral motor system that reflect into an increased and more bilateral activation in elderly subjects. Twelve young and nine elderly healthy right-handed subjects performed a self-initiated brisk right thumb extension while recorded with 32-channel EEG. The aging effect over cortical generators of bereithshaftspotential, reconstructed using cortical current density (CCD) method and a realistic volume conductor, was evaluated in five different periods and in both mesial and lateral motor-related areas. Over-activation occurred mainly at movement initiation in those areas related to simple movements (caudal mesial areas and both sensorimotor cortices) and in contralateral sensorimotor cortex during the post-movement phase. In those areas, the elderly group recruited a larger neuronal population than the young one in the presence of a significantly longer movement. This more likely suggests their reduced selectivity in activating the motor cortex than a compensatory mechanism to produce an optimum performance. Movement duration resulted negatively correlated with pre-SMA activity, suggesting its involvement in movement termination.     

The primary restless legs syndrome pathogenesis depends on the dysfunction of EEG alpha activity

A dopaminergic drug - lisuride exhibited increase in alpha, decrease in beta and slow activities on brain function measured by computerized EEG. It was postulated that reverse EEG changes might play role in the pathogenesis of RLS. During transition from wakefulness to sleep stage 1 changes in alpha activity initiate long-lasting alpha arousal responses and they continue increasingly at sleep stage 2. This dysfunction is probably due to a genetic vulnerability of EEG alpha rhythm and disinhibits the diencephalospinal dopamine system, mostly during sleep but also during wakefulness. The disinhibition produces background for activation of PLMs, disturbing sensations in brainstem and urge to move, motor restlessness at cerebral cortex, generally for legs. All lead to severe insomnia. In RLS patients, forced deviations from alpha to theta or beta activity are unsuitable and resting EEGs reflect a dopamine receptor-specific 'individual sensitivity.' This vulnerability is alleviated after lisuride with suitable CEEG changes.     

点燃癫痫模型大鼠皮层与海马c—fos、c—jun基因的表达

目的：通过点燃癫痫模型大鼠脑内c-fos、c-jun基因表达的观察以探讨癫痫的发病机理。方法：选用大鼠杏仁核快速点燃癫痫模型，应用免疫组织化学技术观察点燃癫痫大鼠的皮层与海马c-fos、c-jun基因的表达。结果：杏仁核点燃癫痫大鼠的皮层与海马c—fos、c-jun基因表达明显增强，阳性细胞数量显著增加。结论：c—fos、c-jun基因的表达与痫性发作的机制相关。     

Estrogen synthesis in the central nucleus of the amygdala following middle cerebral artery occlusion: role in modulating neurotransmission

Stroke-induced lesions of the insular cortex in the brain have been linked to autonomic dysfunction (sympathoexcitation) leading to arrhythmogenesis and sudden cardiac death. In experimental models, systemic estrogen administration in male rats has been shown to reduce stroke-induced cell death in the insular cortex as well as prevent sympathoexcitation. The central nucleus of the amygdala has been postulated to mediate sympathoexcitatory output from the insular cortex. We therefore set out to determine if endogenous estrogen levels within the central nucleus of the amygdala are altered following stroke and if microinjection of estrogen into the central nucleus of the amygdala modulates autonomic tone. Plasma estrogen concentrations were not altered by middle cerebral artery occlusion (22.86+/-0.14 pg/ml vs. 21.24+/-0.33 pg/ml; P>0.05). In contrast, estrogen concentrations in the central nucleus of the amygdala increased significantly following middle cerebral artery occlusion (from 20.83+/-0.54 pg/ml to 76.67+/-1.59 pg/ml; P<0.05). Local infusion of an aromatase inhibitor, letrozole, into the central nucleus of the amygdala at the time of middle cerebral artery occlusion prevented the increase in estrogen concentration suggesting that this increase was dependent on aromatization from testosterone. Furthermore, bilateral microinjection of estrogen (0.5 microM in 200 nl) directly into the central nucleus of the amygdala significantly decreased arterial pressure and sympathetic tone and increased baroreflex sensitivity, and these effects were enhanced following co-injection with either an N-methyl-D-aspartate or non-N-methyl-D-aspartate receptor antagonist. Taken together, the results suggest that middle cerebral artery occlusion resulted in synthesis of estrogen within the central nucleus of the amygdala and that this enhanced estrogen level may act to attenuate overstimulation of central nucleus of the amygdala neurons to prevent middle cerebral artery occlusion-induced autonomic dysfunction.     

Bacterial artificial chromosome transgenic analysis of dynamic expression patterns of regulator of G-protein signaling 4 during development. II. Subcortical regions

A large family of regulator of G protein signaling (RGS) proteins modulates signaling through G-protein-coupled receptors. Previous studies have implicated RGS4 as a vulnerability gene in schizophrenia. To begin to understand structure-function relationships, we have utilized bacterial artificial chromosome (BAC) methods to create transgenic mice that express green fluorescent protein (GFP) under the control of endogenous RGS4 enhancer elements, circumventing the lack of suitable antibodies for analysis of dynamic patterns of expression. This report follows from the accompanying mapping paper in cerebral cortex, with a focus on developmental and mature expression patterns in subcortical telencephalic, diencephalic and brainstem areas. Based on reporter distribution, the data suggest that alterations in RGS4 function will engender a complex phenotype of increased and decreased neuronal output, with developmental, regional, and cellular specificity.     

Effects of aging on signal transmission and transduction systems in the gerbil brain: morphological and autoradiographic study.

The Mongolian gerbil was used as a model of aging because of its relatively short lifespan, genetic homogeneity and the fact that data had been collected previously. Furthermore, gerbils have been widely used in biomedical investigations of stroke and epilepsy. Age-related differences in signal transmission and transduction systems were investigated in brains of three-, 11- and 21-month-old gerbils by morphological and in vitro receptor autoradiographic studies. Morphometric analysis revealed a decreased number of neurons in layer III of the occipital cortex and also a decrease in cerebellar Purkinje cells in 21-month-old animals. However, no statistical differences were observed in the hippocampal formation, the dorsolateral striatum and layer III of the frontal cortex. Autoradiography was used to map muscarinic cholinergic (labeled with [3H]quinuclidinyl benzilate), serotonin2 ([3H]spiperone), dopamine D2 ([3H]spiperone), adenosine A1 ([3H]cyclohexyladenosine), GABAA ([3H]muscimol), naloxone ([3H]naloxone), protein kinase C ([3H]phorbol 12,13-dibutyrate), adenylate cyclase ([3H]forskolin), cyclic AMP ([3H]cyclic AMP) and L-type Ca2+ channels ([3H]PN200-110). Muscarinic cholinergic receptor and protein kinase C, cyclic AMP and L-type Ca2+ channels were significantly decreased in the cerebral cortex and/or in the CA1 subfield of the hippocampus in the 21-month-old group. Muscarinic cholinergic receptor and L-type Ca2+ channel binding sites were significantly reduced in the dentate gyrus. In contrast, protein kinase C was increased in this area in the 21-month-old group. Also, naloxone binding sites were increased in the CA3 subfield, hilus, dentate gyrus and molecular layer of the cerebellum in the 11- and 21-month-old groups. Muscarinic cholinergic, serotonin2 and dopamine D2 receptors and adenylate cyclase were significantly decreased in the striatum. On the other hand, adenosine A1 and GABAA receptors remained unchanged in the 21-month-old group. Although age-related histopathological abnormalities were only observed in the occipital cortex and in the cerebellum, alterations of signal transmission and transduction systems were noticed in all areas examined (e.g. cerebral cortex, CA1 subfield, dentate gyrus and striatum). These data indicate that changes in these receptors and binding sites may be related to dysfunction of learning and memory and to the loss of motor function. The aged gerbil model is a good system for studying aging and is of value for simulating aging after epilepsy and stroke.     

Medial preoptic neuronal responses to connatural females in sexually inactive male monkeys (Macaca fuscata)

The effect of repeated administration of thyroxine on beta-adrenergic receptor binding was studied in several brain regions in the rat using [3H]dihydroalprenolol as a ligand. Thyroxine treatment resulted in an increased density of beta-adrenergic receptors in the cerebral cortex while a decreased binding was found in subcortical tissue representing the thalamus, striatum and parts of the limbic system. There was no change in binding in the cerebellum or in the brainstem. The results indicate that thyroxine may regulate beta-adrenergic receptors in certain brain areas.     

地塞米松对谷氨酸钠致痫大鼠脑电图及GABA免疫反应的影响

为了探讨糖皮质激素的抑痫效应 ,本研究用免疫细胞化学方法和脑电图仪观察了地塞米松对谷氨酸钠致痫大鼠脑电图以及 GABA免疫反应的影响。结果显示 :大鼠在注射谷氨酸钠前 3 0 min经腹腔注射地塞米松 ,能明显减轻严重的癫痫发作症状和脑电图中高电位的痫波发放 ,并使海马齿状回及大脑皮层 GABA阳性神经元表达明显增强。显微图象统计分析 :与致痫组相比 ,抑痫组 GABA阳性神经元平均光密度值增加 ,差异有显著性 (P<0 .0 5 )。上述结果提示 :地塞米松具有抑制谷氨酸钠诱发癫痫的作用 ,其抑痫效应可能与增强 GABA的表达有关。     

动态脑电图对缺血性脑卒中后继发癫痫的研究

目的：探讨缺血性脑卒中后继发性癫癎动态脑电图（AEEG）变化、神经功能的缺损情况及临床疗效与预后.方法：将40例缺血性脑卒中后后继发性癫癎患者设为研究组,回顾其AEEG资料,常规脑电图与动态脑电图检查比较;并与对照组40例缺血性脑卒中后无癫癎发作患者进行比较分析.结果：常规脑电图与动态脑电图检查比较：常规脑电图（REEG）检查中度和重度异常16例,占40％;AEEG检查中度和重度异常的比率为35例,占87.5％,AEEG较REEG检查的中、重度异常比率明显增高,具有统计学差异.研究组患者AEEG异常率占95.0％;发生在脑叶皮质区的患者继发癫癎的概率高于发生在皮质下区的患者,两者间AEEG比较差异有统计学意义（P＜0.05）.结论：AEEG可显著提高卒中后癫癎发作患者的脑电异常检出率,其检查结果对预测癫癎发作、病情变化、预后有着重要的价值.