钾离子通道在癫痫发病机制中的研究进展

癫痫的基本特征是中枢神经反复发作的同步异常放电,而神经元的异常放电与钾离子通道功能紊乱有密切的关系。钾离子通道编码基因突变以及其自身抗体表达异常可导致钾离子通道功能障碍,引发神经元异常放电,临床表现为多形式的癫痫发作。本文介绍了钾离子通道及其抗体在癫痫发病中的作用。     

吗啡毒性对家猫脑皮层电活动及线粒体影响的研究

目的分析吗啡线粒体毒性导致线粒体超微结构改变对家猫脑皮层异常放电的影响,探讨吗啡依赖所致脑功能损害的可能机制。方法将12只家猫按照随机数字表法分成对照组(3只)和吗啡暴露组(9只),用剂量递增法造模成功后,行大脑皮层脑电检测,电镜下观察各脑区皮质神经元线粒体的超微结构改变。结果吗啡暴露组脑电图(EEG)监测显示皮层脑电广泛异常,生理波减少,异常放电频繁出现;电镜示神经元线粒体超微结构在数量、形态、内部膜结构、基质内包涵体各方面均发生改变,表现多样。而对照组EEG及电镜表现均正常。结论吗啡可损害大脑皮层神经元,导致异常放电,这种损害与神经元线粒体超微结构改变关系密切,吗啡线粒体毒性可作为脑细胞能量代谢功能障碍并成为最终导致脑电生理功能活动紊乱的始发机制。     

高频脑深部电刺激对帕金森病模型大鼠丘脑底核神经元放电的影响

目的观察高频电刺激丘脑底核对帕金森病大鼠丘脑底核神经元放电的影响。方法应用6-羟基多巴胺制备偏侧帕金森病大鼠模型,在其丘脑底核区插入刺激电极进行高频电刺激,采用细胞外单位记录的方法记录刺激前和刺激过程中丘脑底核神经元的放电。结果电刺激前对照组和帕金森组丘脑底核神经元放电频率无显著差异,而放电形式不同,对照组大部分丘脑底核神经元表现为规则或不规则放电,帕金森组丘脑底核神经元以爆发放电为主;高频电刺激两组大鼠丘脑底核神经元后,两组丘脑底核神经元放电都主要表现为部分抑制或完全抑制。结论爆发式放电增多可能是帕金森发病潜在的电生理基础。高频电刺激丘脑底核可抑制丘脑底核的异常放电活动,这可能是脑深部电刺激治疗帕金森病的可能机制之一。     

癫痫与N-甲基-D-天冬氨酸受体的研究进展

癫痫(epilepsy)是大脑神经元突发性异常放电,导致短暂的大脑功能障碍的一种慢性疾病,根据异常放电神经元的位置不同而表现多样.全球大约共有7000多万癫痫患者,并且每年有高达240万的新发病例[1].而在我国癫痫疾病的总患病率为7‰,有近600万活动性癫痫患者,且每年以约40万人次的速度增加,因此癫痫称是我国神经系...     

癫痫与N-甲基-D-天冬氨酸受体的研究进展

癫痫( epilepsy)是大脑神经元突发性异常放电,导致短暂的大脑功能障碍的一种慢性疾病,根据异常放电神经元的位置不同而表现多样.全球大约共有7000 多万癫痫患者,并且每年有高达240万的新发病例[1].而在我国癫痫疾病的总患病率为7‰,有近600万活动性癫痫患者,且每年以约40万人次的速度增加,因此癫痫称是我国神...     

培养的海马神经元致癎模型中钙离子的动力学研究

以往的研究证实 ,癫发作中存在神经元内钙离子(Ca2 + )超载现象 ,这种异常的Ca2 + 内流是神经元同步化放电的先决条件 ,同时也能触发神经元一系列病理生理改变 ,导致神经元损伤和可塑性的改变。我们利用培养的海马神经元致模型 ,对神经元内游离钙离子 ([Ca2 + ]i)的时空分布和动力学进行研究 ,以探讨 [Ca2 + ]i在性活动中的作用。材料和方法 :将培养的SD大鼠海马神经元置入去除镁离子的人工脑脊液内诱导癫样放电。实验分为三组 ,分别维持癫样放电 30min、90min和 15 0min。全细胞电流技术全程记录神经元电生理变化。LSCM动态…     

突触素与癫(癎)

癫(癎)(epilepsy)是最常见的神经系统疾病之一,其发病机制复杂,目前认为癫(癎)发病是由于中枢神经系统兴奋与抑制性不平衡导致大脑神经元异常放电所致.     

胆碱能M2受体激动剂及拮抗剂对大鼠脚桥核神经元电活动的影响

目的　在体水平上观察选择性胆碱能M2 受体激动剂oxotremorine和拮抗剂methoctramine对大鼠PPN神经元自发放电频率的影响。方法　 采用玻璃微电极细胞外记录和脚桥核 (pedunculopontinenucleus ,PPN)内微量注射法。 结果　11个神经元在PPN内微量注射高浓度 (每 2 0 0nl含 4 μg)oxotremorine后 ,10个神经元被兴奋 ,放电频率较注射前升高 (2 82± 5 9) % ,1个神经元放电频率无明显变化 ;低浓度 (每 2 0 0nl含 0 .2 μg)oxotremorine注射后 ,11个神经元中 ,有 6个神经元被抑制 ,放电频率较注射前降低 (98± 2 ) % ,5个神经元被兴奋 ,放电频率较前对照升高(6 80± 32 4 ) %。 12个神经元在PPN内微量注射高浓度 (每 2 0 0nl含 4 μg)methoctramine后 ,4个神经元被兴奋 ,放电频率较前对照升高 (4 0 9± 133) % ,6个神经元被抑制 ,放电频率较注射前降低 (86± 8) % ,2个放电频率无显著变化 ;低浓度 (每 2 0 0nl含 0 .4 μg)methoctramine注射后 ,12个神经元中 ,有 5个神经元被兴奋 ,放电频率较前对照升高 (117± 15 ) % ,6个神经元被抑制 ,放电频率较注射前降低 (79± 11) % ,1个放电频率未受明显影响。 结论　 胆碱能M2 受体通过直接和间接作用对PPN神经元的电活动进行调节     

扭转痉挛患者基底节的电生理研究

目的 观察扭转痉挛患者基底节神经元的电活动特点。方法 在对6例扭转痉挛患者行微电极导向脑内核团毁损术治疗的同时,利用微电极记录技术分别对4例患者的内苍白球、2例患者的丘脑底核神经元电活动进行了记录和分析。结果 内苍白球神经元主要表现为高度不规律的持续低频群发放电,间有暂歇,其平均自发放电频率为(26.4±13.9)Hz,电活性较低。丘脑底核神经元主要表现为不规律的发放,其平均自发放电频率为(49.1±9.2)Hz,电活性较高。结论 扭转痉挛患者基底节存在功能异常。     

帕金森病猴丘脑底核神经元的电生理特性

目的探讨帕金森病(PD)猴模型丘脑底核(STN)神经元的电生理特性,为研究帕金森病的病理生理过程提供动物实验依据。方法应用颈内动脉注射MPTP建立PD猴模型。在立体定向仪引导下应用细胞外记录的方法记录"造模"前后猴病理及正常生理状态下STN神经元的放电活动,并对其放电模式进行分析。结果电生理记录显示STN神经元放电频率在生理状态下为2.03±1.12Hz;在病理状态下为9.58±0.85 Hz(P<0.01)。在生理状态下有20个(20/35,57.14%)神经元呈现簇发放电,有15个(15/35,42.86%)神经元呈现连续放电;在PD病理状态下有10个(10/12,85.71%)神经元呈现簇发放电,有2个(2/12,14.29%)神经元呈现连续放电(P<0.05)。生理状态下STN神经元的ISI序列散在分布于30～980ms之间;在PD病理状态下当STN神经元呈连续放电时,ISI分布于50～360ms之间,在150ms以下有一个分布密集条带,当STN神经元呈簇发放电时,ISI分布于30～470ms之间,在40ms以下有一个分布密集条带。结论PD猴模型STN神经元较生理状态下放电频率明显增加,其放电模式也有明显变化,簇状放电模式比例增大,ISI序列发生明显变化。     

Environmental factors in the development and progression of late-onset Alzheimer＇s disease

Late-onset Alzheimer＇s disease （LOAD） is an age-related neurodegenerative disorder characterized by gradual loss of synapses and neurons, but its pathogenesis remains to be clarified. Neurons live in an environment constituted by neurons themselves and glial cells. In this review, we propose that the neuronal degeneration in the AD brain is partially caused by diverse environmental factors. We first discuss various environmental stresses and the corresponding responses at different levels. Then we propose some mechanisms underlying the specific pathological changes, in particular, hypothalamic-pituitary adrenal axis dysfunction at the systemic level; cerebrovascular dysfunction, metal toxicity, glial activation, and Aβ toxicity at the intercellular level; and kinase-phosphatase imbalance and epigenetic modification at the intracellular level. Finally, we discuss the possibility of developing new strategies for the prevention and treatment of LOAD from the perspective of environmental stress. We conclude that environmental factors play a significant role in the development of LOAD through multiple pathological mechanisms.     

Disrupted structural and functional brain connectomes in mild cognitive impairment and Alzheimer＇s disease

Alzheimer＇s disease （AD） is the most common type of dementia, comprising an estimated 60-80% of all dementia cases. It is clinically characterized by impairments of memory and other cognitive functions. Previous studies have demonstrated that these impairments are associated with abnormal structural and functional connections among brain regions, leading to a disconnection concept of AD. With the advent of a combination of non-invasive neuroimaging （structural magnetic resonance imaging （MRI）, diffusion MRI, and functional MRI） and neurophysiological techniques （electroencephalography and magnetoencephaJography） with graph theoretical analysis, recent studies have shown that patients with AD and mild cognitive impairment （MCI）, the prodromal stage of AD, exhibit disrupted topological organization in large-scale brain networks （i.e., connectomics） and that this disruption is significantly correlated with the decline of cognitive functions. In this review, we summarize the recent progress of brain connectomics in AD and MCI, focusing on the changes in the topological organization of large-scale structural and functional brain networks using graph theoretical approaches. Based on the two different perspectives of information segregation and integration, the literature reviewed here suggests that AD and MCI are associated with disrupted segregation and integration in brain networks. Thus, these connectomics studies open up a new window for understanding the pathophysiological mechanisms of AD and demonstrate the potential to uncover imaging biomarkers for clinical diagnosis and treatment evaluation for this disease.     

高血压脑出血的显微外科治疗进展

高血压脑出血（Hypertensive intrac-rebral hemorrhage,HICH）是具有高发病率、高病死率、高致残率的急性脑血管疾病,占所有脑卒中患者的10%-20%,早期病死率可高达49.4%。随着人口老龄化,其发病率逐年提高;而外科手术的干预,使其病死率有所下降,但致残率居高不下。如何提高手术疗效和患者生存质量,一直是神经外科医师努力的方向。微侵袭血肿清除术因其手术创伤小,恢复快,是目前国内治疗高血压脑出血的重要手段。     

Edema and neuronal apoptosis in the hippocampus and cortex of elderly rats following transient cerebral ischemia/reperfusion injury

BACKGROUND： Previous studies of cerebral ischemia have used young animals, with an ischemic time greater than 5 minutes （safe time limit）. Despite an increased understanding of neuronal apoptosis, it remains uncertain whether brief cerebral ischemic events of 5 minutes or less damage brain tissue in elderly rodents. OBJECTIVE： To investigate the effects of transient cerebral ischemia （5 minutes）/reperfusion injury on brain cortical and hippocampal edema, aquaporin-4 （AQP-4） expression, and neuronal apoptosis in aged rats, and to compare ischemic sensitivity between cortex and hippocampus. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Cerebrovascular Disease, Qingdao University Medical School from April 2008 to March 2009. MATERIALS： Rabbit anti-AQP-4 polyclonal antibody, TUNEL kit, and SABC immunohistochemistry kit were purchased from Wuhan Boster Bioengineering, China. METHODS： A total of 160 healthy, male, aged 19-21 months, Wistar rats were randomly assigned to 4 groups： sham-surgery, and ischemia 1-, 3-, and 5-minute groups, with 40 rats in each group. The global cerebral ischemia model was established using the Pusinelli four-vessel occlusion, and the three cerebral ischemia groups were subdivided into reperfusion 12-hour, 1-, 2-, 3-, and 7-day subgroups, with 8 rats in each subgroup. The sham-surgery group was subjected to exposure of the first cervical bilateral alar foramina and bilateral common carotid arteries. MAIN OUTCOME MEASURES： The dry-wet weight assay was used to measure brain water content and histopathology of the cortex and hippocampus was observed following hematoxylin-eosin staining. In addition, cortical and hippocampal AQP-4 expression was detected by streptavidin-biotin complex immunohistochemistry, and neuronal apoptosis was detected by the TUNEL method. RESULTS： There was no significant difference in brain water content or AQP-4 expression in the cortex and hippocampus between ischemia 1- and 3-minute groups and the sham-surgery group or brain water content or AQP-4 expression in the cortex between ischemia 5-minute group and sham-surgery group （P 〉 0.05）. However, brain water content and AQP-4 expression in the hippocampus after 5 minutes of cerebral ischemia were significantly increased compared with the sham-surgery group （P 〈 0.05 or P 〈 0.01）. Several TUNEL-positive cells were observed in the cortex and hippocampus of the sham-surgery group and ischemia 1-minute group, as well as in the cortex of the ischemia 3-minute group. In addition, the number of apoptotic neurons in the hippocampus of ischemia 3-minute group and in the cortex and hippocampus of ischemia 5-minute group was significantly increased （P 〈 0.05 or P 〈 0.01 ）. Neuronal apoptosis was increased after 12 hours of ischemia/reperfusion, and it reached a peak by 2 days （P 〈 0.01）. CONCLUSION： Transient cerebral ischemia （5 minutes） resulted in increased hippocampal edema, AQP-4 expression, and neuronal apoptosis. Moreover, cerebral ischemia had a greater effect on neuronal apoptosis than brain edema or AQP-4 expression, and the hippocampus was more sensitive than the cortex.     

雷公藤内酯对癫痫大鼠神经元P13K／Akt／mTOR蛋白的影响

目的通过检测癫痫大鼠海马神经元P13K、Akt和mTOR蛋白表达,探讨雷公藤内酯抑制癫痫大鼠神经元凋亡的分子机制。方法30只大鼠随机分为对照组、海人酸组、雷公藤内酯干预组,免疫组化法检测各组大鼠海马神经元P13K、Akt和mTOR蛋白的表达情况。结果海人酸组神经元胞体皱缩,形态不规则,数量减少,而雷公藤内酯干预组神经元的数量和形态与对照组相似,海人酸组海马神经元P13K、Akt、ITITOR蛋白表达与对照组比较均减少,而雷公藤内酯干预组海马神经元的P13K、Akt、mTOR蛋白表达均较海人酸组增加,差异均有统计学意义（P〈0．05）。结论雷公藤内酯可能通过上调P13K／Akt／mTOR信号通路蛋白表达对癫痫大鼠海马神经元发挥保护作用。     

神经内镜联合亚低温治疗高血压基底节区脑出血

目的 探讨神经内镜联合亚低温在治疗高血压基底节区脑出血中的临床应用价值.方法 回顾性分析我院神经内镜治疗高血压基底节区脑出血患者40例的临床资料,并对治疗结果进行分析.结果 神经内镜治疗组22例(甲组),神经内镜联合亚低温治疗组18例(乙组),术后3个月根据GCS评分,甲组恢复良好1例,中残4例,重残6例,植物生存6例,死亡5例;乙组恢复良好4例,中残8例,重残3例,植物生存1例,死亡2例,两组比较差异有统计学意义(P＜0.05).两组颅内压比较第1天两者差异不明显,但第2、3天亚低温组颅内压明显降低.结论 神经内镜是治疗高血压基底节区脑出血较为有效的手术方式,联合亚低温治疗能有效降低颅内压,改善术后神经功能恢复,具有较好的临床应用价值.     

1例痰瘀同治精神疾患临床心得

现代医学把精神分裂症分若干类：狂躁型、忧郁型、强迫型、青春型、痴呆型等,西医一直把治疗精神分裂症的重点放在大脑的治疗上。我的经验是：痰和瘀血是精神分裂症的非常重要的原因,特别是肝、心、头部及其经络的痰和瘀血是关键。笔者治愈1例报道如下。     

心理干预对恶性肿瘤患者疼痛及焦虑抑郁状态的影响

目的 心理干预对恶性肿瘤患者疼痛及焦虑抑郁状态的影响.方法 将85例伴有疼痛的恶性肿瘤患者随机分为对照组42例和观察组43例,对照组给予三阶梯止痛治疗,观察组在给予三阶梯治疗的基础上对患者进行心理干预,采用问卷调查方式进行焦虑自评量表(SAS),抑郁自评量表( SDS)的评定.结果 伴有疼痛的恶性肿瘤病人存在着相当严重程度的焦虑/抑郁情绪,观察组疼痛治疗效果及焦虑抑郁状态均好于对照组,两组差异有统计学意义(P＜0.05).结论 伴有疼痛的恶性肿瘤患者普遍存在抑郁焦虑的心理问题,并且随着癌痛程度加重而加重,心理干预不仅对改善疼痛有着重要的作用;而且能够改善恶性肿瘤患者焦虑抑郁的心理状态,提高患者生活质量.     

阿尔茨海默病治疗的研究进展

阿尔茨海默病（AD）是一种隐匿性起病,进行性恶化的神经退行性疾病,临床最初表现为认知功能障碍,并有可能在5～10年内完全衰退。患者往往伴随严重的记忆力丧失、精神行为异常、人格改变、言语功能障碍,无法独立生活,最终近乎于植物状态。Ferri等采用DISMOD软件在全球60岁以上人群中估计,全球的痴呆患者人数到2040年将达到8llO万左右。