Disturbance of Oxidative Phosphorylation in the Mitochondria of Late Post-Traumatic Epileptic Nidus

We measured the rate of oxygen consumption by the mitochondria from the brain tissues of rabbits within a remote period after light cranio-cerebral trauma. One and six months after traumatization, oxidative phosphorylation in rabbits of the experimental groups demonstrated no significant difference from that in the control group. Yet, after a 12-month-long interval, clear differences were observed within the cortical zone with post-traumatic epileptic nidus. The coefficient of energy production decreased, and the process of oxidative phosphorylation became uncoupled. When succinate was used as a substrate for oxidation, we observed significant decreases in the rate of oxygen consumption in ADP phosphorylation and in the coefficient of respiration control. A significant decrease in the rate of oxygen consumption in the resting state (V ₂), the absence of disturbances in the respiration control, and preservation of a sufficient reserve ATPase activity were characteristic features when glutamate was used as a substrate. It seems probable that such shifts in oxidative phosphorylation can result in creation of an excessive glutamate pool and provide excessive epileptogenic glutamatergic activation of the neurons.     

Upregulation of SYNGAP1 expression in mice and human neurons by redirecting alternative splicing

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Stretch-activated ion channel TMEM63B associates with developmental and epileptic encephalopathies and progressive neurodegeneration

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电刺激右后背海马诱导双侧前背海马网络癫痫

目的 :急性强直电刺激右侧后背HPC诱导双侧HPC癫痫电网络形成的细胞机制。方法 :强直电刺激 (6 0Hz,2s,0 .4～ 0 .6mA)大鼠右后背HPCCA1基树突区 ,每隔 10min刺激一次 ,施加 10个刺激串。结果 :①分别抑制双侧CA1神经元单位放电频率 ,对侧的抑制效应更明显 (对侧 :6 2 .94 %± 3.6 8% ;同侧 :36 .6 1%± 3.14 % ,P <0 .0 1) ,出现抑制后爆发式放电。随着刺激串数的增加 ,抑制作用逐渐减弱。②同步原发性网络和单位后放电 ,以同侧CA1多见 (P<0 .0 1)。③ 90Hz或 12 0Hz原发性或继发性网络后放电仅仅累及同侧CA1。④对侧CA3基树突区网络与下托神经元单位放电出现同步继发性后放电 ,反复发作 ,持续约数小时。结论 :电刺激诱导的对侧HPC抑制后爆发式放电和长时程、反复发作的网络与单个神经元同步继发性后放电可能是跨半球癫痫网络形成的重要表现形式。     

Comparison of DNA variants in the PRNP and NF1 regions between bovine spongiform encephalopathy and control cattle

DNA from 252 bovine spongiform encephalopathy (BSE) cattle and 376 non-diseased control cattle were genotyped for nine loci in the prion protein (PRNP) gene region, three loci in the neurofibromin 1 (NF1) region and four control loci on different chromosomes. The allele and genotype frequencies of the control loci were similar in BSE and control cattle. In the analysed 7.4 Mb PRNP region, the largest differences between BSE and control cattle were found for the loci REG2, R16 and R18, which are located between +300 and +5600 bp, spanning PRNP introns 1 to 2. Carriers of the REG2 genotype 128/128 were younger at BSE diagnosis than those with the other genotypes (128/140 or 140/140). The predominant haplotype REG2 128 bp-R18 173 bp occurred more frequently (P < 0.001), and the second-most frequent haplotype (REG2 140 bp-R18 175 bp) occurred less frequently (P < 0.05) in BSE than in control cattle. The largest frequency differences between BSE and control groups were observed in the Brown Swiss breed. Across all breeds, most of the same alleles and haplotypes of the PRNP region were associated with BSE. In the 23-cM NF1 region, associations with BSE incidence were found for the RM222 allele and for the DIK4009 genotype frequencies. Cattle carrying RM222 genotypes with the 127- or 129-bp alleles were about half a year older at BSE incidence than those with other genotypes. Across the breeds, different alleles and genotypes of the NF1 region were associated with BSE. The informative DNA markers were used to localize the genetic disposition to BSE and may be useful for the identification of the causative DNA variants.     

Review. The origin of the prion agent of kuru: molecular and biological strain typing

Kuru is an acquired human prion disease that primarily affected the Fore linguistic group of the Eastern Highlands of Papua New Guinea. The central clinical feature of kuru is progressive cerebellar ataxia and, in sharp contrast to most cases of sporadic Creutzfeldt-Jakob disease (CJD), dementia is a less prominent and usually late clinical feature. In this regard, kuru is more similar to variant CJD, which also has similar prodromal symptoms of sensory disturbance and joint pains in the legs and psychiatric and behavioural changes. Since a significant part of the clinicopathological diversity seen in human prion disease is likely to relate to the propagation of distinct human prion strains, we have compared the transmission properties of kuru prions with those isolated from patients with sporadic, iatrogenic and variant CJD in both transgenic and wild-type mice. These data have established that kuru prions have prion strain properties equivalent to those of classical (sporadic and iatrogenic) CJD prions but distinct from variant CJD prions. Here, we review these findings and discuss how peripheral routes of infection and other factors may be critical modifiers of the kuru phenotype.     

40例慢性脑型血吸虫病的脑电图分析

目的:了解脑型血吸虫病脑电图(EEG)的脑电活动状况,为临床诊断与治疗提供参考。方法:收集1997~2004年临床诊断为脑型血吸虫病的40例EEG资料,主要分析异常EEG的脑电活动状况与异常程度、临床分型及预后的关系。结果:31例出现不同程度的EEG异常改变,异常率为77.5%,其中癫痫性为70%;脑瘤型为100%。绝大部分EEG检查是患者经治疗后作的。治疗前后均作了EEG检查的仅9例。治疗前,9例均有不同程度异常,治疗后7例有不同程度改善,2例恢复正常。结论:EEG对脑型血吸虫病的诊断及预后的评价有参考价值。     

传染性海绵状脑病的诊断进展和存在的问题

传染性海绵状脑病是由朊病毒引起的人和多种哺乳动物以神经退行性变化为主要特征的一种慢性致死性传染病。引起这类疾病的病原因子是一种编码宿主蛋白的PrPC转变为异常的PrPSC沉积在大脑,导致传染性海绵状脑病的发生。本文从临床症状识别、组织病理学诊断、致病性朊蛋白检测、生物学测定以及毒株鉴定等几个方面作一回顾和总结,为揭示朊病毒疾病致病机理和诊断研究提供借鉴。     

红藻氨酸癫痫大鼠海马GFAP基因调控蛋白表达的变化

目的和方法：用Southwestern印迹从红藻氨酸（KA）癫痫大鼠海马结构中筛选调控胶质原纤维酸性蛋白（GFAP）基因表达的DNA结合蛋白;并观察其在海马内表达变化的规律,旨在从基因调控水平深入探讨癫痫反复发作形成的神经病理学机制。结果：Southwestern印迹的实验显示海马结构内有两种调控GFAP基因表达的序列特异的DNA结合蛋白,分子量分别为39kDa和35.5kDa;KA后1d,两种调控蛋白的表达即开始增加,5－7d时表达显著增加,3周时表达最多,3个月时表达仍很高。结论：KA通过上调调控GFAP基因表达的转录因子,使海马GFAP过量表达,提示该转录调控因子很可能参与一次KA后癫痫反复发作的形成。