氟桂利嗪对青霉素致癎大鼠海马细胞单位放电特征的影响

目的：探讨青霉素癫癎模型大鼠海马神经元单位放电的特征。方法：36只Wistar雄性健康大鼠,随机分为正常对照组、癫癎模型组、癫癎预处理组,各12只。①正常对照组记录单位放电后处死;②癫癎模型组用青霉素钠按600万U／kg体重腹腔注射制作成癫癎模型,记录单位放电后处死;③癫癎预处理组制作模型前用盐酸氟桂利嗪按20mg／kg体重每隔12h灌胃共两次,第二次给药后2h制作成癫癎模型,然后作单位放电记录后处死。结果：①正常对照组大鼠共记录到24个单位海马神经元放电;②癫癎模型组共记录到78个单位海马神经元放电;③癫癎预处理组共记录到47个单位海马神经元放电。与正常对照组比较,癫癎模型组海马神经元单位放电频率增加,放电形式多为混合型,差异有极显著意义（P〈0．01）;与癫癎模型组比较,癫癎预处理组海马神经元单位放电频率降低,差异有统计学意义（P〈0．05）。结论：①癫癎大鼠是以暴发放电为主的混合型放电,抽搐时多表现为束簇状;②盐酸氟桂利嗪对癫癎大鼠放电有显著的抑制作用。     

高胆红素血症新生儿血清神经元特异性烯醇化酶水平变化及意义

目的探讨血清神经元特异性烯醇化酶（s—NSE）水平与新生儿行为神经测定（NBNA）的相关性,探讨s—NSE在急性胆红素脑病（ABE）发生、发展中的价值。方法对63例高胆红素血症新生儿在高胆期及黄疸消退后分别采用电化学发光免疫法测定s—NSE及行NBNA,生后1、3、6个月追踪随访,并与24例正常新生儿对照。结果高胆期：s-NSE水平随血清总胆红素（TSB）升高而升高,各组s—NSE水平比较差异有统计学意义（F=56．287,P〈0．01）;高胆组NBNA评分明显下降,NBNA评分随TSB升高而降低,各组NBNA评分比较差异有统计学意义（F=50．247,P〈0．01）;s—NSE水平与NBNA评分间呈显著负相关（r=-0．609,P〈0．01）。高胆消退后,s—NSE水平均有明显下降,NBNA评分同步上升。结论高胆红素血症患儿s—NSE浓度显著升高,与NBNA评分呈负相关,可以作为临床早期监测新生儿是否进入ABE的危险期的一个生物学指标。     

新生儿缺血缺氧性脑病血清神经元特异性烯醇化酶与Apgar评分及头颅CT的关系

目的探讨缺血缺氧性脑损伤新生儿血清神经元特异性烯醇化酶（NSE）的变化与Apgar评分及头颅CT的关系。方法50例窒息新生儿在出生后6～12h采集血标本,2h内分离血清,用电发光化学法检测NSE浓度。5d左右行头颅CT检查。结果影像学检查阳性组（23例）和阴性组（27例）,血清NSE浓度分别为（34±10）ug／L和（15±6）ug/L（P〈0．01）,血清NSE浓度与5分钟Apgar评分呈负相关（r=-0．812,P〈0．01）。结论外周血清NSE水平可作为临床早期评价窒息新生儿脑损伤严重程度的客观指标。     

Development and pharmacological modulation of embryonic stem cell-derived neuronal network activity

Embryonic stem cells can be differentiated into neurons of diverse neurotransmitter-specific phenotypes. While the time course of functional progression of ES cell-derived neural precursors towards mature neurons has been described in detail on single-cell level, the temporal development and pharmacological modulation of ES cell-derived neuronal network activity have not been explored yet. Neuronal network activity can be assessed by the microelectrode array (MEA) technology that allows simultaneous monitoring of the electrical activity exhibited by entire populations of neurons over several weeks or months in vitro. We demonstrate here that ES cell-derived neural precursors cultured on MEAs for 5 to 6 weeks develop neuronal networks with oscillating and synchronous spike patterns via distinct states of activity and change electrophysiological characteristics even after 5 to 6 weeks in culture pointing towards late maturational processes. These processes were accompanied by an increasing density of presynaptic vesicles. Furthermore, we demonstrated that ES cell-derived network activity was sensitive to synaptically acting drugs indicating that pharmacologically susceptible neuronal networks were generated. Thus, the MEA technology represents a powerful tool to describe the temporal progression of stem cell-derived neural populations towards mature, functioning neuronal networks that can be applied to investigate pharmacologically active compounds.     

Expression patterns of MLC1 protein in the central and peripheral nervous systems

Mutations in MLC1 cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), a disorder characterized clinically by macrocephaly, deterioration of motor functions, epilepsy and mental decline. Recent studies have detected MLC1 mRNA and protein in astroglial processes. In addition, our group previously reported MLC1 expression in some neurons in the adult mouse brain. Here we performed an exhaustive study of the expression pattern of MLC1 in the developing mouse brain by means of optic and electron microscopy. In the central nervous system, MLC1 was detected mainly in axonal tracts early in development. In addition, MLC1 was also observed in the peripheral nervous system and in several sensory epithelia, as retina or saccula maculae. Post-embedding immunogold experiments indicated that MLC1 is localized in astrocyte-astrocyte junctions, but not in the perivascular membrane, indicating that MLC1 is not a component of the dystrophin-glycoprotein complex. In neurons, MLC1 is located at the plasma membrane and vesicular structures. Our data provide a mouse MLC1 expression map that could be useful to understand the phenotype of MLC patients, and suggested that MLC disease is caused by an astrocytic and a neuronal dysfunction.     

Neuronal Apoptosis Revealed by Genomic Analysis: Integrating Gene Expression Profiles with Functional Information

Apoptosis is a key physiological response that occurs during development of the nervous system, resulting in the death of nearly half of the embryonic neuronal population. Aberrant apoptotic mechanisms are thought to contribute significantly to many neurological disorders including Alzheimer’s disease. Although many experiments in the past have demonstrated the requirement of de novo gene expression during neuronal apoptosis, the complete spectrum of genes involved in distinct temporal domains is mostly unknown. To begin a comprehensive survey of the gene-based molecular mechanisms that underlie neuronal apoptosis, we have used the unprecedented experimental opportunities that genome sequences and the development of DNA microarray technology now provide to perform genome-wide expression analysis in different paradigms of neuronal apoptosis. In order to extract knowledge from gene expression information we have developed new informatics applications that enable clustering methods based on semantic characteristics, such as gene ontologies. This review will highlight the use of a genomic approach to identify the molecular program underlying neuronal apoptosis and illustrate how a semantic clustering method can be useful to extract more knowledge from microarray data.     

The bradykinin B2 receptor mediates hypoxia/reoxygenation induced neuronal cell apoptosis through the ERK1/2 pathway

The bradykinin B2 receptor (B2R) mediates many physiological processes such as hypotension, inflammation and blood-vessel permeability. Hypoxia/reoxygenation (H/R) induces neuronal cell apoptosis. It was found that B2R expression was enhanced in primary cultured cortical neurons after H/R treatment. Addition of bradykinin (BK) alleviated the neuronal damage from H/R. This protective effect of BK was inhibited by the B2R antagonist, HOE140, and the ERK1/2 antagonist, PD98059. The phosphorylation of ERK1/2 was increased under H/R, and the addition of BK enhanced this effect. These results indicate that B2R plays an important role in protecting neurons from damage induced by H/R and this effect may function through the ERK1/2 pathway.     

Function and regulation of TRP family channels in C. elegans

Seventeen transient receptor potential (TRP) family proteins are encoded by the C. elegans genome, and they cover all of the seven TRP subfamilies, including TRPC, TRPV, TRPM, TRPN, TRPA, TRPP, and TRPML. Classical forward and reverse genetic screens have isolated mutant alleles in every C. elegans trp gene, and their characterizations have revealed novel functions and regulatory mechanisms of TRP channels. For example, the TRPC channels TRP-1 and TRP-2 control nicotine-dependent behavior, while TRP-3, a sperm TRPC channel, is regulated by sperm activation and required for sperm–egg interactions during fertilization. Similar to their vertebrate counterparts, C. elegans TRPs function in sensory physiology. For instance, the TRPV channels OSM-9 and OCR-2 act in chemosensation, osmosensation, and touch sensation, the TRPA member TRPA-1 regulates touch sensation, while the TRPN channel TRP-4 mediates proprioception. Some C. elegans TRPM, TRPP, and TRPML members exhibit cellular functions similar to their vertebrate homologues and have provided insights into human diseases, including polycystic kidney disease, hypomagnesemia, and mucolipidosis type IV. The availability of a complete set of trp gene mutants in conjunction with its facile genetics makes C. elegans a powerful model for studying the function and regulation of TRP family channels in vivo.     

经颅磁刺激对海马原代神经元突起生长的影响

目的 观察经颅磁刺激(transcranial magnetic stimulation,TMS)对体外培养的海马原代神经元突起生长及形态的影响,并初步探讨磁刺激对细胞生长发育的影响机制.方法 体外培养的海马原代神经元分为正常培养组(C组),假刺激组(S组),40%最大刺激强度组(M1组),60%最大刺激强度组(M2组),培养细胞24 h后开始磁刺激,每天固定时间刺激,刺激的频率为1 Hz,磁刺激最大输出强度为1.9 T,每天刺激3次,每次20序列,每个序列间隔1 s,每次间隔1 min,连续刺激5 d,刺激源距离细胞1.0 cm.刺激结束后进行免疫荧光染色,观察原代神经元突起形态学改变,比较突起生长数目的 改变及SYN-I表达的改变.结果 TMS 5 d后观察细胞生长状态良好,细胞与细胞间联系较多,部分细胞表现为多突起生长.M1、M2组2个突起的神经元占总神经元的比例分别为(45.6±14.9)%和(45.2±15.6)%,较C组和S组明显增多,差异有统计学意义(P＜0.05);3个及3个以上突起的神经元占总神经元的比例分别为(30.3±10.8)%和(29.3±11.5)%,较C组和S组亦明显增多,差异有统计学意义(P＜0.05).M2组的SYN-I mRNA的表达较C、S两组增高,差异有统计学意义(P＜0.05).结论 TMS可以促进体外培养的海马原代神经元突起的生长.