不同首剂匹罗卡品制作颞叶癫痫大鼠模型的研究

目的:研究不同首次剂量匹罗卡品对氯化锂-匹罗卡品颞叶癫痫大鼠模型诱发成功率、死亡率的影响。方法:90只SD大鼠随机分为三组,每组首次使用匹罗卡品剂量:A组10mg/kg、B组20mg/kg、C组30mg/kg;随后采用多次注射10mg/kg匹罗卡品,比较3组癫痫持续状态诱发成功率、死亡率的差异。结果:A、B、C组癫痫持续状态诱发成功率分别为66.7%、90%、93.3%。其中A组与B组之间诱发成功率差异有统计学意义,P<0.05;C组与B组之间相比,差异无统计学意义,P>0.05。三组死亡率分别为20%、23.3%、57.1%,其中A组与B组之间差异无统计学差异,P>0.05,;C组与其它两组相比较差异有统计学差异,P<0.05。结论:首次剂量20mg匹罗卡品,然后10mg多次反复注射,癫痫持续状态诱发成功率高、死亡率低,是一种理想的颞叶癫痫模型。     

人脑默认网络方向图：基于7TfMRI的动态因果模型

近年来,默认网络是认知神经科学领域的研究热点之一,已有研究报告它可能参与了多种认知活动,而且某些精神疾病也与其异常活动相关.但默认网络内主要脑区之间的有向连接关系(有效连接模式)尚不明确.本研究使用国际前沿的谱动态因果模型算法,基于7T高分辨率静息态功能磁共振数据,对默认网络4个核心脑区之间的有效连接模式进行了探索.实验结果发现,默认网络内后扣带回接受内侧前额叶、双侧顶下叶的信息输入,可能扮演着信息集合中心的角色,而双侧顶下叶对内侧前额叶、后扣带回都有信息输入,在默认网络内可能起到信息驱动和调节的功能.本研究首次报道了基于7T功能磁共振数据得到的默认网络有向连接图谱,对于我们更深入理解默认网络的功能具有帮助,对相关精神疾病的研究具有潜在的参考应用价值.     

基于动脉自旋标记技术的内侧颞叶癫痫病人脑血流灌注成像研究北大核心CSCD

基于动脉自旋标记(arterial spin labeling,ASL)技术,分析内侧颞叶癫痫(mesialtemporal lobe epilepsy,mTLE)患者大脑血流灌注(perfusion)的改变情况。在静息态下,采集了30例内侧颞叶癫痫伴单侧海马硬化发作间期患者(其中左侧16例,右侧14例)及22例健康志愿者的ASL数据,并通过计算获取其相对脑血流量(relative CBF,rCBF)及灌注不对称率(asymmetric index,AI)。癫痫病人与正常人的比较结果表明:左侧mTLE患者在两侧海马旁回、梭状回、额叶、颞叶和患侧海马回及岛叶,右侧mTLE患者在两侧海马回、海马旁回、额叶、颞叶和患侧杏仁核及岛叶,rCBF均有所下降,且患侧的下降程度和范围均大于对侧。说明mTLE患者的海马硬化可能导致了痫灶区功能异常,并通过癫痫的发作影响到全脑。     

基于ReHo方法的颞叶癫痫功能磁共振成像研究

癫痫是一种以神经活动同步性异常增高为特征的中枢神经系统疾病。作者利用基于局域一致性(regional homogeneity,ReHo)分析方法的功能磁共振成像技术对内侧颞叶癫痫(medial temporal lobe epilepsy,mTLE)进行了研究。观察颞叶癫痫病人相比正常对照组局域一致性的改变情况。结果表明:在静息状态下,病人大脑的局域一致性在某些脑区较正常人高,主要集中在海马、丘脑、顶叶;另外在某些脑区的局域一致性较正常人低,主要集中在小脑后叶。提示该方法可检出癫痫活动造成的局部脑组织血氧水平信号同步性的改变,进而达到对癫痫活动的定位检测。     

基于纤维束追踪空间统计的内侧颞叶癫痫患者弥散张量成像研究

本研究通过分析磁共振弥散张量成像(diffusion tensor imaging,DTI)数据,观察内侧颞叶癫痫(mesial temporal lobe epilepsy,mTLE)患者大脑白质的改变。46例伴有单侧海马硬化的内侧颞叶癫痫患者(24例左侧颞叶癫痫和22例右侧颞叶癫痫),以及42例年龄和性别匹配的正常志愿者纳入本研究。采用基于纤维束追踪的空间统计分析方法(track-based spatialstatistics,TBSS),主要观察患者各向异性系数(fractionsal anisotropy,FA)的变化。结果发现,与正常志愿者相比,左侧mTLE患者FA降低的区域呈双侧分布,稍偏向患侧,胼胝体、上纵束、下纵束、内囊前肢等白质双侧都有异常,而扣带束、下额枕束只在左脑显著降低;右侧mTLE患者FA降低主要见于右脑,包括胼胝体、上纵束、下纵束和钩束等。结果表明,基于TBSS方法的DTI研究揭示了伴有海马硬化的mTLE患者的脑白质异常,有助于加深对mTLE病理生理机制的了解。     

fMRI颞叶癫痫默认模式网络的研究

许多功能磁共振研究已经发现人脑的一些皮层区域在静息状态下出现共激活,这些区域形成连通的功能网络,称为"默认模式网络"。本文研究颞叶癫痫患者的默认模式网络,运用独立成分分析(Independent component analysis)分离出12例颞叶癫痫患者和12例正常对照的默认模式网络,进行组内分析得到两组被试的统计图,进行组间分析比较两组被试的默认模式网络的差异。结果表明默认模式网络均存在于颞叶癫痫患者和正常对照中,然而,在默认模式包含的网络中,颞叶癫痫患者前扣带回腹侧(ventral anterior cingulated cortex,vACC)、前额中分(medial prefrontal cortex,MPFC)、楔前叶(precuneus)、以及海马旁回区域比正常对照表现出代谢增强。这一结果有助于从脑功能的角度了解癫痫患者某些临床症状的发病机理,为今后癫痫诊治的发展提供一定的帮助。     

基于ICA的颞叶癫痫缺省模式网络的研究

很多fMRI研究表明部分癫痫患者缺省模式网络存在中断现象,但均采用广义线性模型的假设驱动方法。作者尝试运用独立成分分析（independent component analysis, ICA）分离出l5例单侧颞叶癫痫（temporal lobe epilepsy,TLE）患者和17例正常对照的缺省模式网络,并采用拟合度值（goodness-of-fit scores）分析对感兴趣成分进行挑选,将其结果进行组内分析和组间分析。结果表明颞叶癫痫患者的缺省模式网络犬部分区域功能连接度下降,以前额叶和同侧颞上回为著,这可能是由于颞叶癫痫患者的大脑功能内源性组织发生破坏所致。拟合度值下降表明缺省模式网络激活区域为单侧TLE患者提供了一个灵敏的生物信号特征。     

MST3在颞叶癫痫模型小鼠海马的表达变化

目的观察海人酸(kainic acid,KA)所致癫痫(epilepsy,EP)小鼠海马Ste20蛋白激酵素(MST3)表达水平的变化,探讨MST3在癫痫发病过程中的可能作用。方法选用成年雄性小鼠,并随机分成模型组和对照组。模型组小鼠侧脑室注射2μL(100 ng/μL)KA,分别于术后3、8、24 h收集动物标本以进行检测。使用RT-PCR和Western Blot测定MST3 mRNA含量和MST3蛋白动态表达变化,应用免疫组化观察MST3在海马的表达分布与特点。结果与正常对照组相比,模型组海马组织内MST3mRNA的表达随时间持续升高,24 h达到高峰;MST3的蛋白表达也表现出同样的动态升高趋势;术后3～24 h的模型组海马免疫组化检测显示,模型组MST3主要以海马齿状回、门回区、CA3区域表达增加为主,并且这些区域表达逐渐递增。结论随着时间的推移,MST3表达水平呈现逐渐增加趋势,可能与神经元损伤造成的凋亡之间有密切的关系,提示MST3可能在癫痫发病过程中起重要作用。     

基于动态因果模型研究盐酸哌甲酯对大脑默认网络效应连接的调制作用北大核心CSCD

本文基于静息态功能磁共振成像研究18名健康男性大学生志愿者在服用盐酸哌甲酯药物后大脑默认网络的效应连接变化。应用动态因果模型方法分析比较在服用安慰剂和盐酸哌甲酯药物两种条件下静息态默认网络的效应连接的区别。静息态的动态因果模型分析以文献研究提供的网络模型为先验基础,将低频波段信号（0.01~0.08 Hz）作为默认网络的驱动输入,再根据盐酸哌甲酯药物对节点间不同连接的调节作用设计32种动态因果可能性模型,最终通过拟合分析和贝叶斯模型选择得到最优模型及模型参数。结果表明,在静息条件下默认网络的内侧前额叶到后扣带回、两侧顶下小叶到内侧前额叶以及右侧顶下小叶到后扣带回的效应连接分别表现为促进状态,而左侧顶下小叶到后扣带回却表现为抑制连接。进一步地,根据盐酸哌甲酯药物与安慰剂条件的连接参数的配对统计比较发现,盐酸哌甲酯显著调节右侧顶下小叶到内侧前额叶皮质的连接（t=2.724,P=0.016）,使其由弱促进状态转变为抑制状态,但对其它连接无显著影响。本研究结果表明,盐酸哌甲酯药物对正常志愿者大脑静息态默认网络的效应连接具有显著的调制作用。     

杏仁核点燃模型癫痫样放电传播途径研究

目的 :探讨杏仁核点燃模型癫痫样放电的传播途径。方法 :选择健康Wistar大鼠 3 0只以电刺激杏仁核的方式制作杏仁核点燃癫痫模型 ,于右侧杏仁核、左侧海马及右侧额叶皮质埋植电极记录脑电活动 ,观察电刺激杏仁核时在杏仁核、海马及额叶皮质出现癫痫样放电的潜伏期、最低刺激强度及癫痫样放电的持续时间。结果 :杏仁核出现癫痫样放电时 ,海马及皮质均未记录到癫痫样放电。而当杏仁核、海马及皮质三处出现癫痫样放电时的最低刺激强度依次增大 ,潜伏期依次延长 ,海马处癫痫样放电的持续时间最长。结论 :杏仁核点燃模型癫痫样放电可能由杏仁核经海马传至皮层 ,海马可能为癫痫样放电传播的重要结构     

Linear and Nonlinear Measures and Seizure Anticipation in Temporal Lobe Epilepsy

In a recent paper, we showed that the value of a nonlinear quantity computed from scalp electrode data was correlated with the time to a seizure in patients with temporal lobe epilepsy. In this paper we study the relationship between the linear and nonlinear content and analyses of the scalp data. We do this in two ways. First, using surrogate data methods, we show that there is important nonlinear structure in the scalp electrode data to which our methods are sensitive. Second, we study the behavior of some simple linear metrics on the same set of scalp data to see whether the nonlinear metrics contain additional information not carried by the linear measures. We find that, while the nonlinear measures are correlated with time to seizure, the linear measures are not, over the time scales we have defined. The linear and nonlinear measures are themselves apparently linearly correlated, but that correlation can be ascribed to the influence of a small set of outliers, associated with muscle artifact. A remaining, more subtle relation between the variance of the values of a nonlinear measure and the expectation value of a linear measure persists. Implications of our observations are discussed.     

颞叶癫痫脑“默认模式”的fMRI研究

功能磁共振成像(functional magnetic resonance imaging,fMRI)被用于检测静息时脑功能神经网络.作者运用静息fMRI检测海马硬化颞叶癫痫(temporal lobe epilepsy,TLE)脑"默认模式",采用感兴趣区域功能连接分析检测16例TLE患者和16名正常对照静息时脑的"默认模式",并进行组内和组间分析.研究发现,与正常对照相比,TLE静息时海马、颞极、额叶、颞叶、壳核及楔前叶等脑区与后扣带回的功能连接增强.研究结果表明TLE患者的固有脑功能组织模式有可能出现紊乱.这一研究将有助于从脑功能的角度了解癫痫患者某些临床症状的发病机理,为今后癫痫诊治的发展提供一定的帮助.     

Protective Effect of Resveratrol against Kainate-induced Temporal Lobe Epilepsy in Rats

Resveratrol (Res) is a phytoalexin produced naturally by several plants, which has multi functional effects such as neuroprotection, anti-inflammatory, and anti-cancer. The present study was to evaluate a possible anti-epileptic effect of Res against kainate-induced temporal lobe epilepsy (TLE) in rat. We performed behavior monitoring, intracranial electroencepholography (IEEG) recording, histological analysis, and Western blotting to evaluate the anti-epilepsy effect of Res in kainate-induced epileptic rats. Res decreased the frequency of spontaneous seizures and inhibited the epileptiform discharges. Moreover, Res could protect neurons against kainate-induced neuronal cell death in CA1 and CA3a regions and depressed mossy fiber sprouting, which are general histological characteristics both in TLE patients and animal models. Western blot revealed that the expression level of kainate receptors (KARs) in hippocampus was reduced in Res-administrated rats compared to that in epileptic ones. These results suggest that Res is a potent anti-epilepsy agent, which protects against epileptogenesis and progression of the kainate-induced TLE animal. The authors Z. Wu and Q. Xu contributed equally to this work.     

Reduction of Hippocampal Collapsin Response Mediated Protein-2 in Patients with Mesial Temporal Lobe Epilepsy

Although the syndrome of mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis has been elaborated in recent years, pathogenesis and pathomechanisms are still elusive. Performing protein hunting in hippocampus of patients with MTLE we detected derangement of collapsin response mediated protein-2 (CRMP-2). Hippocampal tissue from controls and MTLEs was taken and two-dimensional gel electrophoresis with subsequent MALDI-MS-characterisation was applied. The proteomic approach identified 13 spots unambiguously assigned to CRMP-2. Three spots at molecular weight 55 kDa showed a significant decrease in MTLE and other 3 spots at 65 kDa showed deranged in MTLE. Immunoblotting revealed two bands at 65 and 55 kDa in the control group whereas the 55 kDa band was extremely low expressed in MTLE. CRMP-2 is required to induce axonal outgrowth and maintaining neuronal polarity in hippocampal neurons and the significant decrease of this protein may represent or underlie impaired neuronal plasticity, neurodegeneration, wiring of the brain in MTLE and may explain abnormal migration. Therefore, the decrease of CRMP-2 may well contribute to the understanding of the still unclear pathomechanisms involved in MTLE.     

Identification of the Pain Process by Cold Stimulation: Using Dynamic Causal Modeling of Effective Connectivity in Functional Near-Infrared Spectroscopy (fNIRS)

Background

Pain is an unpleasant sensory and emotional experience followed by anxiety, depression, and frustration. Functional Near-Infrared Spectroscopy (fNIRS) as an optical technique identifies the brain functional networks by investigating connectivity between functionally linked of different anatomical regions in response to pain stimulation.

不同术式对颞叶癫痫患者术后认知功能、记忆能力以及生活质量的影响

目的:探讨不同术式对颞叶癫痫患者术后认知功能、记忆能力以及生活质量的影响。方法:选取2014年2月～2018年4月期间我院收治的103例颞叶癫痫患者为研究对象,根据随机数字表法将患者分为单侧前颞叶切除术(ATL)组(n=51,给予ATL治疗)和选择性海马杏仁核切除术(SAH)组(n=52,给予SAH治疗),比较两组患者的手术疗效、术后认知功能、记忆能力、生活质量以及并发症。结果:两组术后6个月临床总有效率比较差异无统计学意义(P0.05)。两组患者术后6个月生活质量量表各项评分均较术前升高(P0.05)。两组患者术后6个月总智商(FIQ)、语言智商(VIQ)评分均较术前升高,且SAH组高于ATL组(P0.05)。两组术后6个月优势半球侧记忆商数(MQ)评分降低,非优势半球侧MQ评分升高(P0.05);SAH组术后6个月非优势半球侧MQ评分高于ATL组(P0.05)。两组患者术后并发症发生率比较无统计学差异(P0.05)。结论:颞叶癫痫患者采用ATL、SAH术式治疗,可获得相似的治疗效果,安全性均较好,但SAH术式在保护患者的认知功能及记忆能力方面更优。     

Glucose-dependent insulinotropic peptide receptor expression in the hippocampus and neocortex of mesial temporal lobe epilepsy patients and rats undergoing pilocarpine induced status epilepticus

The glucose-dependent insulinotropic peptide receptor (GIPR) has been implicated with neuroplasticity and may be related to epilepsy. GIPR expression was analyzed by immunohistochemistry in the hippocampus (HIP) and neocortex (Cx) of rats undergoing pilocarpine induced status epilepticus (Pilo-SE), and in three young male patients with left mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) treated surgically. A combined GIPR immunohistochemistry and Fluoro-Jade staining was carried out to investigate the association between the GIPR expression and neuronal degeneration induced by Pilo-SE. GIPR was expressed in the cytoplasm of neurons from the HIP CA subfields, dentate gyrus (DG) and Cx of animals and human samples. The GIPR expression after the Pilo-SE induction increases significantly in the HIP after 1 h and 5 days, but not after 12 h or 50 days. In the Cx, the GIPR expression increases after 1 h, 12 h and 5 days, but not 50 days after the Pilo-SE. The expression of GIPR 12 h after Pilo-SE was inversely proportional to the Fluoro-Jade staining intensity. In the human tissue, GIPR expression patterns were similar to those observed in chronic Pilo-SE animals. No Fluoro-Jade stained cells were observed in the human sample. GIPR is expressed in human HIP and Cx. There was a time and region dependent increase of GIPR expression in the HIP and Cx after Pilo-SE that was inversely associated to neuronal degeneration.     

β淀粉样蛋白和tau蛋白磷酸化程度与颞叶癫痫患者认知缺陷相关性研究

摘要 目的：探究β淀粉样蛋白（Aβ）和tau蛋白磷酸化程度与颞叶癫痫患者认知缺陷相关性。方法：2019年至2020年于我院接受治疗的70例颞叶癫痫患者作为本研究的实验组,同时纳入同期健康体检者70例作为本研究的对照组。对比两组一般临床指标、外周血清中β淀粉样蛋白和tau蛋白磷酸化程度;评估两组的智力、记忆力和认知功能障碍;通过Person法分析β淀粉样蛋白和tau蛋白磷酸化程度与颞叶癫痫患者认知缺陷相关性。结果：（1）比较显示实验组的Aβ1-28蛋白、Aβ1-40蛋白、tau蛋白和p-tau蛋白均高于对照组,但Aβ1-42蛋白低于对照组（P<0.05）;（2）实验组语言智商（VIQ）、操作智商（PIQ）以及总智商（FIQ）评分均低于对照组（P<0.05）;（3）实验组评估低于对照组（P<0.05）;（4）实验组的MoCA评分显著低于对照组（P<0.05）;（5）Aβ1-28蛋白、Aβ1-40蛋白、Tau蛋白和p-tau蛋白与颞叶癫痫患者认知缺陷存在正相关关系;Aβ1-42蛋白与颞叶癫痫患者认知缺陷则存在负相关关系（P<0.05）。结论：颞叶癫痫患者认知缺陷与tau蛋白磷酸化程度、Aβ1-28蛋白、Aβ1-42蛋白和Aβ1-40蛋白水平具有相关性,可作为认知缺陷的判断指标,为体检或临床发现颞叶癫痫患者是否存在认知功能缺陷提供依据。     

Network Analysis of the Default Mode Network Using Functional Connectivity MRI in Temporal Lobe Epilepsy

Functional connectivity MRI (fcMRI) is an fMRI method that examines the connectivity of different brain areas based on the correlation of BOLD signal fluctuations over time. Temporal Lobe Epilepsy (TLE) is the most common type of adult epilepsy and involves multiple brain networks. The default mode network (DMN) is involved in conscious, resting state cognition and is thought to be affected in TLE where seizures cause impairment of consciousness. The DMN in epilepsy was examined using seed based fcMRI. The anterior and posterior hubs of the DMN were used as seeds in this analysis. The results show a disconnection between the anterior and posterior hubs of the DMN in TLE during the basal state. In addition, increased DMN connectivity to other brain regions in left TLE along with decreased connectivity in right TLE is revealed. The analysis demonstrates how seed-based fcMRI can be used to probe cerebral networks in brain disorders such as TLE.