Spatial learning and psychomotor performance of C57BL/6 mice: age sensitivity and reliability of individual differences

Two tests often used in aging research, the elevated path test and the Morris water maze test, were examined for their application to the study of brain aging in a large sample of C57BL/6JNia mice. Specifically, these studies assessed: (1) sensitivity to age and the degree of interrelatedness among different behavioral measures derived from these tests, (2) the effect of age on variation in the measurements, and (3) the reliability of individual differences in performance on the tests. Both tests detected age-related deficits in group performance that occurred independently of each other. However, analysis of data obtained on the Morris water maze test revealed three relatively independent components of cognitive performance. Performance in initial acquisition of spatial learning in the Morris maze was not highly correlated with performance during reversal learning (when mice were required to learn a new spatial location), whereas performance in both of those phases was independent of spatial performance assessed during a single probe trial administered at the end of acquisition training. Moreover, impaired performance during initial acquisition could be detected at an earlier age than impairments in reversal learning. There were modest but significant age-related increases in the variance of both elevated path test scores and in several measures of learning in the Morris maze test. Analysis of test scores of mice across repeated testing sessions confirmed reliability of the measurements obtained for cognitive and psychomotor function. Power calculations confirmed that there are sufficiently large age-related differences in elevated path test performance, relative to within age variability, to render this test useful for studies into the ability of an intervention to prevent or reverse age-related deficits in psychomotor performance. Power calculations indicated a need for larger sample sizes for detection of intervention effects on cognitive components of the Morris water maze test, at least when implemented at the ages tested in this study. Variability among old mice in both tests, including each of the various independent measures in the Morris maze, may be useful for elucidating the biological bases of different aspects of dysfunctional brain aging.     

In vivo synaptic plasticity in the dentate gyrus of mice deficient in the neural cell adhesion molecule NCAM or its polysialic acid

The neural cell adhesion molecule NCAM and its associated polysialic acid (PSA) play important roles in synaptic plasticity in the CA1 and/or CA3 regions of the hippocampus in vitro. Here, we address the question of whether NCAM and PSA are involved in regulation of synaptic transmission and plasticity also in vivo at synapses formed by entorhinal cortex axons in the dentate gyrus of mice anaesthetized with urethane. We show that basal synaptic transmission, measured as the slope of field excitatory postsynaptic potentials, was reduced strongly in mice lacking ST8SiaII/STX, the enzyme involved in polysialylation of NCAM in stem cell-derived immature granule cells, but not in mice deficient either in the NCAM glycoprotein or the enzyme ST8SiaIV/PST involved in polysialylation of NCAM in mature neurons. Strikingly, only mice deficient in NCAM, but not in PST or STX, were impaired in long-term potentiation (LTP) induced by theta-burst stimulation, suggesting that LTP in the dentate gyrus depends on the NCAM glycoprotein alone rather than on its associated PSA. As also patterns of synaptic activity during and immediately after induction of LTP were impaired in NCAM-deficient mice, it is likely that induction of LTP requires NCAM. These data are the first to describe that NCAM is necessary for induction of synaptic plasticity in identified synapses in vivo and suggest that polysialylation of NCAM expressed by immature granule cells in the dentate gyrus supports development of basal excitatory synaptic transmission in this region.     

Cardiotoxic effects of Loxosceles intermedia spider venom and the recombinant venom toxin rLiD1

Loxosceles spider bites cause many human injuries worldwide. Injections in mice of whole Loxosceles (L.) intermedia venom or a recombinant toxin (rLiD1) produce systemic symptoms similar to those detected in envenomed humans. This animal model was used to characterize the effects of Loxosceles intermedia venom in cardiac tissues. L. intermedia antigens were detected by ELISA in kidney, heart, lung and liver of experimentally envenomed mice. In addition, rLiD1 binding to cardiomyocytes was demonstrated by immunofluorescence and confocal microscopy. Furthermore, isolated perfused heart preparations and ventricular cardiomyocytes from envenomed mice showed heart function impairment, and a significant increase of I_Ca,L density and intracellular Ca²⁺ transients, respectively. Thus, L. intermedia spider venom, as shown through the use of the recombinant toxin rLiD1, causes cardiotoxic effects and a protein from the sphingomyelinase D family plays a key role in heart dysfunction. Thus, L. intermedia spider venom and the Loxtox rLiD1 play a key role in heart dysfunction.     

11种临床路径疾病围术期预防性使用抗菌药物情况调查与分析

目的：调查分析11种临床疾病中抗菌药物的预防使用情况。方法：随机抽取2009年12月—2010年3月手术患者出院病历65份,采用药物利用评估（drug use evaluation,DUE）进行抗菌药物合理性评价。结果：65份病例中抗菌药物使用率为86.15%,术前使用抗菌药物的为33.85%;术前使用了抗菌药物的病例中术前2h内用药的为66.15%;术后使用时间大于72h占89.33%。使用的抗菌药物中,头孢米诺、哌拉西林/舒巴坦、美洛西林应用的频次较高。综合分析11种临床路径中,子宫肌瘤、声带息肉、股骨颈骨折、乳癌围术期抗菌药物合理应用仅占15.38%。结论：临床路径中围术期抗菌药物的应用不合理现象较为突出,药物日剂量控制较好,但用药级别偏高,术后抗菌药物的使用时间偏长。     

健康教育路径在脑卒中住院患者中的应用评价

健康教育路径是对病人进行健康教育的时间表和计划表,使护士知道做什么,怎么做。在运用健康教育路径的时候,护理人员要将护理程序思维贯穿其中,通过评估-诊断-计划-实施-评价,不断完善健康教育工作,使病人和家属能够在护理人员的指导下配合完成。2009年2～7月,我们对256例脑卒中住院患者实施健康教育路径,取得满意效果。现报告如下。     

大容量全肺灌洗治疗尘肺临床路径的变异因素分析

目的分析大容量全肺灌洗治疗尘肺临床路径中的变异因素,研究临床路径实施中存在的问题并提出改进措施。方法观察228例实施临床路径管理的大容量全肺灌洗患者。在临床路径表上记录每例患者每日目标完成情况,对于偏离路径的病例在变异记录单上记录其变异原因,并分析临床路径变异的影响因素。结果通过对变异事项的统计得出:发生变异的病例达50.43%。来源于操作因素变异发生率25.44%、医院系统变异发生率24.56%、负性变异发生率达40.35%。结论通过对变异结果分析,可及早发现重要的变化趋势,不断修改、完善CP,使之形成一个良性的医疗过程     

c-fos Protooncogene expression in rat hippocampus and entorhinal cortex following tetanic stimulation of the perforant path

The elevated expression of the c-fos protooncogene has been proposed to be a marker of cell activation leading to a long term cellular response. In this communication we compared the c-fos mRNA accumulation in the hippocampus (i.e. postsynaptic cells) and entorhinal cortex (i.e. presynaptic cells) following high (tetanic) and low frequency electrical stimulation of the perforant path. Using Northern blot analysis we have found that high frequency stimulation elevates c-fos expression in both hippocampus and entorhinal cortex, and the increase of c-fos mRNA levels in the entorhinal cortex is less pronounced, but longer lasting, than in the hippocampus. Slight increase of c-fos mRNA levels has been also observed in low frequency treated animals in the entorhinal cortex, but not in the hippocampus. These findings raise the question about differences in mechanisms involved in c-fos activation in both parts of the brain after stimulation which evokes long term potentiation (LTP) of synaptic efficacy.     

Development of spontaneous seizures over extended electrical kindling: I. Electrographic, behavioral, and transfer kindling correlates

The present study was aimed at evaluating an extended kindling model of spontaneous epilepsy. Behavioral and electrographic responses to repeated kindling of either the perforant path or amygdala were monitored for up to 300 trials. Kindling initially led to generalized convulsions equivalent to the level 5 seizure on the rating scale developed by Racine. The evoked seizures became progressively more complex with additional kindling, which was described by a 10-stage classification system. The highest stage (stage 10) was achieved when the kindling stimulation evoked two or more bouts of level 5 seizures combined with running and jumping fits. These more complex seizures developed over the course of amygdala, but not perforant path kindling. Electrographic seizures from both the amygdala and dentate gyrus increased in duration and amplitude during the early phase of kindling, but did not correlate with motor seizure development beyond level 5. During the late phase of kindling, the dentate gyrus afterdischarge amplitude decreased and became dissociated from the behavioral seizures. Manifestations of spontaneously recurring seizures were seen in the majority of animals, but spontaneous seizures of level 4 or greater were observed in only five rats. The second part of this study examined kindling transfer effects, the efficacy of kindling a new site after the completion of the initial (in this case extended) kindling protocol. The effect depended on both primary and secondary site location. When the amygdala served as primary site, perforant path transfer was complete in some animals but absent in others. No transfer occurred in the opposite direction, from the perforant path to the amygdala. Finally, transfer effects in the dentate gyrus, which was tested as tertiary site, were complete. Previous studies have found weaker transfer effects in the dentate when kindling to the standard stage 5 level.     

Profiling of endogenous brain peptides and small proteins: Methodology, computer-assisted analysis, and application to aging and lesion models

Significant advances in the technology for the isolation of peptides and small proteins have permitted their identification as biologic markers and enhanced the study of the posttranslational life of proteins. The protocol described here examined large numbers of tissue-derived peptides and small proteins, extracted in low pH and boiled so that proteolysis was interrupted. These were then fractionated batchwise using size exclusion and ion-exchange chromatography. Profiles of species in the peptide pools were then generated on reverse-phase high-performance liquid chromatography (HPLC). The HPLC profiles were evaluated with chromatographic analysis software to identify and quantify peptide peaks and with data compilation programs to sort this information into spreadsheets for comparison of profiles among groups. Using rodent brain, the effects of postmortem delay or age were examined. Postmortem delay produced limited alterations to the profiles, but the effect of age was more pronounced. Many changes were apparent until 12 months, after which the profiles became more constant. Additional peptide profiling of the hippocampus demonstrated changes in peptide content as a function of perforant pathway ablation. The major strengths of HPLC-mediated peptide profiling are that it lends itself to automation and can be used to detect changes in peptides and small proteins among experimental groups or subjects without any prior assumptions concerning which ones might be altered.