BACKGROUND & AIMS: :This article describes the effects of dexmedetomidine (DEX) - the active ingredient of medetomidine, which is the latest popular sedative for functional magnetic resonance imaging (fMRI) in rodents - on multiple unit activity, local field potential (LFP), cerebral blood flow (CBF), pial vessel diameter [indicative of cerebral blood volume (CBV)], and blood oxygenation level-dependent (BOLD) fMRI. These measurements were obtained from the rat somatosensory cortex during 10 s of forepaw stimulation. We found that the continuous intravascular systemic infusion of DEX (50 μg/kg/h, doses typically used in fMRI studies) caused epileptic activities, and that supplemental isoflurane (ISO) administration of ~0.3% helped to suppress the development of epileptic activities and maintained robust neuronal and hemodynamic responses for up to 3 h. Supplemental administration of N(2)O in addition to DEX nearly abolished hemodynamic responses even if neuronal activity remained. Under DEX + ISO anesthesia, spike firing rate and the delta power of LFP increased, whereas beta and gamma power decreased, as compared with ISO-only anesthesia. DEX administration caused pial arteries and veins to constrict nearly equally, resulting in decreases in baseline CBF and CBV. Evoked LFP and CBF responses to forepaw stimulation were largest at a frequency of 8-10 Hz, and a non-linear relationship was observed. Similarly, BOLD fMRI responses measured at 9.4 T were largest at a frequency of 10 Hz. Both pial arteries and veins dilated rapidly (artery, 32.2%; vein, 5.8%), and venous diameter returned to baseline slower than arterial diameter. These results will be useful for designing, conducting and interpreting fMRI experiments under DEX sedation.

背景与目标： ：本文描述了右美托咪定（DEX）-美托咪定的活性成分-它是啮齿动物功能磁共振成像（fMRI）的最新流行镇静剂-对多种单位活性，局部场电位（LFP）和脑血流的影响（CBF），脉管直径[指示脑血容量（CBV）]和血液氧合水平依赖性（BOLD）fMRI。这些测量是在前脚刺激10 s的过程中从大鼠的体感皮层获得的。我们发现，持续进行的DEX（50μg/ kg / h，fMRI研究中通常使用的剂量）的血管内全身输注引起癫痫活动，补充异氟烷（ISO）的用量约0.3％有助于抑制癫痫活动的发展。维持强劲的神经元和血液动力学反应长达3小时。即使保留神经元活性，除DEX外，N（2）O的补充给药几乎消除了血流动力学反应。与仅使用ISO的麻醉相比，在DEX ISO麻醉下，峰值放电频率和LFP的德尔塔功率增加，而β和γ功率下降。施用DEX可使颈动脉和静脉几乎均等地收缩，从而导致基线CBF和CBV降低。诱发的LFP和CBF对前爪刺激的响应最大，频率为8-10 Hz，并且观察到非线性关系。同样，在9.4 T下测得的BOLD fMRI反应最大，频率为10 Hz。颈动脉和静脉都迅速扩张（动脉，占32.2％；静脉，占5.8％），静脉直径恢复到基线的速度比动脉直径慢。这些结果对于在DEX镇静下设计，进行和解释fMRI实验将是有用的。

BACKGROUND & AIMS: BACKGROUND:In Xenopus the bone morphogenetic protein growth and differentiation factor 6 (GDF6) is expressed at the edge of the neural plate, and within the anterior neural plate including the eye fields. Here we address the role of GDF6 in neural and eye development by morpholino knockdown experiments. RESULTS:We show that depletion of GDF6 (BMP13) resulted in a reduction in eye size, loss of laminar structure and a reduction in differentiated neural cell types within the retina. This correlated with a reduction in staining for Smad1/5/8 phosphorylation indicating a decrease in GDF6 signalling through loss of phosphorylation of these intracellular mediators of bone morphogenetic protein (BMP) signalling. In addition, the Pax6 expression domain is reduced in size at early optic vesicle stages. Neural cell adhesion molecule (NCAM) is generally reduced in intensity along the neural tube, while in the retina and brain discreet patches of NCAM expression are also lost. GDF6 knock down resulted in an increase in cell death along the neural tube and within the retina as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. CONCLUSION:Our data demonstrate that GDF6 has an important role in neural differentiation in the eye as well as within the central nervous system, and that GDF6 may act in some way to maintain cell survival within the ectoderm, during the normal waves of programmed cell death.

背景与目标： 背景：在非洲爪蟾中，骨形态发生蛋白生长和分化因子6（GDF6）在神经板的边缘以及包括眼野在内的前神经板内表达。在这里，我们通过吗啉代敲除实验解决了GDF6在神经和眼睛发育中的作用。
结果：我们显示，GDF6（BMP13）耗竭导致眼睛大小减少，层状结构丧失以及视网膜内分化的神经细胞类型减少。这与Smad1 / 5/8磷酸化染色的减少有关，表明通过骨形态发生蛋白（BMP）信号传导的这些细胞内介质的磷酸化损失，GDF6信号传导减少。此外，Pax6表达域的大小在早期的囊泡阶段被减小。神经细胞粘附分子（NCAM）沿神经管的强度通常会降低，而在视网膜和大脑中，NCAM表达的谨慎斑块也会丢失。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）染色确定，GDF6敲低导致沿神经管和视网膜内细胞死亡增加。
结论：我们的数据表明，GDF6在眼睛以及中枢神经系统内的神经分化中具有重要作用，并且在正常的程序性细胞死亡浪潮中，GDF6可能以某种方式维持外胚层中的细胞存活。 。

BACKGROUND & AIMS: :Only a few methods permit researchers to study selected regions of the central and peripheral nervous systems with a spatial and time resolution sufficient to image the function of neural structures. Usually, these methods cannot analyse deep-brain regions and a high-resolution method, which could repeatedly probe dynamic processes in any region of the central and peripheral nervous systems, is much needed. Here, we show that fibred fluorescence microscopy-which uses a small-diameter fibre-optic probe to provide real-time images-has the spatial resolution to image various neural structures in the living animal, the consistency needed for a sequential, quantitative evaluation of axonal degeneration/regeneration of a peripheral nerve, and the sensitivity to detect calcium transients on a sub-second timescale. These unique features should prove useful in many physiological studies requiring the in situ functional imaging of tissues in a living animal.

背景与目标： ：只有几种方法可以使研究人员以足够的空间和时间分辨率来研究中枢神经系统和周围神经系统的选定区域，以对神经结构的功能进行成像。通常，这些方法无法分析深脑区域，因此非常需要高分辨率的方法，该方法可以反复探查中枢神经系统和周围神经系统任何区域的动态过程。在这里，我们显示纤维荧光显微镜法（使用小直径光纤探针提供实时图像）具有空间分辨率，可以对活体动物的各种神经结构进行成像，具有连续定量地评估动物所需的一致性。周围神经的轴突变性/再生，以及在亚秒级范围内检测钙瞬变的敏感性。这些独特的特征在许多需要活体动物组织原位功能成像的生理研究中应被证明是有用的。

BACKGROUND & AIMS: BACKGROUND:Individuals with HIV disease often must adhere to complex medication regimens. To date, regimen complexity has not been examined in the literature using standardized procedures incorporating all important elements of antiretroviral (ARV) regimens. OBJECTIVE:This article presents a novel method of quantifying regimen complexity using objective criteria addressing the factors that may complicate adherence to ARV regimens. METHODS:Part 1 of this article describes the development of the Antiretroviral Regimen Complexity (ARC) Index scoring system. Based on input from pediatric and adult patients, caregivers of pediatric patients, and health care professionals, this comprehensive system includes the number of medications, dosing schedules, administration methods, special instructions, and required preparations associated with ARV regimens. Weights are applied for each of these factors to produce an overall score representing the regimen's level of complexity. Part 2 of this article presents reliability and validity data for the system. RESULTS:The ARC Index demonstrates excellent test-retest and interrater reliability as well as strong construct and discriminant validity. An on-line version of this system minimizes computation errors. CONCLUSIONS:Although modifications may be necessary for patients requiring nonstandard dosing instructions, preliminary evidence supports the utility of this measure as a reliable and valid indicator of the complexity of antiretroviral treatment regimens.

背景与目标： 背景：艾滋病毒感染者通常必须遵守复杂的药物治疗方案。迄今为止，文献中尚未使用纳入抗逆转录病毒（ARV）方案所有重要要素的标准化程序来检查方案的复杂性。
目的：本文提出了一种新的量化方案复杂性的方法，该方法使用客观标准解决了可能使遵守ARV方案复杂化的因素。
方法：本文的第1部分描述了抗逆转录病毒药物复杂性（ARC）指数评分系统的开发。基于小儿和成年患者，小儿患者的看护者以及医疗保健专业人员的输入，此综合系统包括药物数量，给药方案，给药方法，特殊说明以及与抗逆转录病毒疗法相关的所需制剂。将权重应用于这些因素中的每一个，以产生代表方案复杂程度的总分。本文的第2部分介绍了系统的可靠性和有效性数据。
结果：ARC指数显示出优异的重测性和跨度可靠性，以及强大的构造和判别效度。该系统的在线版本最大程度地减少了计算错误。
结论：尽管对于需要非标准剂量指导的患者可能需要进行修改，但初步证据支持该措施可作为抗逆转录病毒治疗方案复杂性的可靠且有效的指标。

BACKGROUND & AIMS: :Stem cells have been widely assumed to be capable of replacing lost or damaged cells in a number of diseases, including Parkinson's disease (PD), in which neurons of the substantia nigra (SN) die and fail to provide the neurotransmitter, dopamine (DA), to the striatum. We report that undifferentiated human neural stem cells (hNSCs) implanted into 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated Parkinsonian primates survived, migrated, and had a functional impact as assessed quantitatively by behavioral improvement in this DA-deficit model, in which Parkinsonian signs directly correlate to reduced DA levels. A small number of hNSC progeny differentiated into tyrosine hydroxylase (TH) and/or dopamine transporter (DAT) immunopositive cells, suggesting that the microenvironment within and around the lesioned adult host SN still permits development of a DA phenotype by responsive progenitor cells. A much larger number of hNSC-derived cells that did not express neuronal or DA markers was found arrayed along the persisting nigrostriatal path, juxtaposed with host cells. These hNSCs, which express DA-protective factors, were therefore well positioned to influence host TH+ cells and mediate other homeostatic adjustments, as reflected in a return to baseline endogenous neuronal number-to-size ratios, preservation of extant host nigrostriatal circuitry, and a normalizing effect on alpha-synuclein aggregation. We propose that multiple modes of reciprocal interaction between exogenous hNSCs and the pathological host milieu underlie the functional improvement observed in this model of PD.

背景与目标： 干细胞已被广泛认为能够替代许多疾病中丢失或受损的细胞，包括帕金森氏病（PD），在该疾病中黑质（SN）的神经元死亡而无法提供神经递质多巴胺（DA） ），到纹状体。我们报告说，未分化的人类神经干细胞（hNSCs）植入1-甲基-4-苯基-1,2,3,6-四氢吡啶处理的帕金森氏灵长类动物得以存活，迁移并通过行为改善定量评估了功能影响这种DA赤字模型，其中帕金森氏征与降低的DA水平直接相关。少量的hNSC后代分化为酪氨酸羟化酶（TH）和/或多巴胺转运蛋白（DAT）免疫阳性细胞，表明病变成年宿​​主SN内和周围的微环境仍然允许响应性祖细胞发展DA表型。发现大量不表达神经元或DA标记的hNSC衍生细胞沿着持续的黑纹状体路径排列，并与宿主细胞并列。这些表达DA保护因子的hNSCs处于良好位置，可以影响宿主TH细胞并介导其他稳态调节，这体现在恢复基线内源性神经元数与大小之比，保留现存宿主黑质纹状体回路和对α-突触核蛋白聚集的归一化作用。我们建议外源性hNSCs和病理宿主环境之间的相互交互的多种模式奠定了在这种PD模型中观察到的功能改善的基础。

BACKGROUND & AIMS: :Cross-linking of the B cell antigen receptor (BCR) leads to the activation of three types of intracellular protein tyrosine kinases. These tyrosine kinases then phosphorylate signaling components to activate a variety of signaling reactions, including phosphatidylinositol 4,5-bisphosphate hydrolysis, Ras activation, and phosphatidylinositol 3-kinase activation. Each of these signaling reactions, and also the signaling molecules Vav and HS1, appears to be important for at least some of the many types of B cell responses to antigen. The complexity of BCR signaling reactions may be required to allow the B cell to respond in a number of distinct ways to antigen (proliferation, survival, apoptosis, maturational arrest, etc.) depending on the maturation state of the B cell, the location in the body, the physical nature of the antigen, and the possible presence of the antigen in complex with antibody or complement components.

背景与目标： B细胞抗原受体（BCR）的交联导致三种类型的细胞内蛋白酪氨酸激酶的激活。然后，这些酪氨酸激酶使信号转导成分磷酸化，以激活各种信号转导反应，包括磷脂酰肌醇4,5-双磷酸酯水解，Ras活化和磷脂酰肌醇3-激酶活化。这些信号传导反应中的每一个，以及信号传导分子Vav和HS1，似乎对B细胞对抗原的多种反应中的至少一些都很重要。可能需要BCR信号传导反应的复杂性，以使B细胞以多种不同的方式对抗原作出反应（增殖，存活，凋亡，成熟停滞等），具体取决于B细胞的成熟状态，在B细胞中的位置人体，抗原的物理性质以及与抗体或补体成分复合的抗原的可能存在。

BACKGROUND & AIMS: This paper reports on the application of an artificial neural network to the clinical analysis of ophthalmological data. In particular a 2-dimensional Kohonen self-organising feature map (SOM) is used to analyse visual field data from glaucoma patients. Importantly, the paper addresses the problem of how the SOM can be utilised to accommodate the noise within the data. This is a particularly important problem within longitudinal assessment, where detecting significant change is the crux of the problem in clinical diagnosis. Data from 737 glaucomatous visual field records (Humphrey Visual Field Analyzer, program 24-2) are used to train a SOM with 25 nodes organised on a square grid. The SOM clusters the data organising the output map such that fields with early and advanced loss are at extreme positions, with a continuum of change in place and extent of loss represented by the intervening nodes. For each SOM node 100 variants, generated by a computer simulation modelling the variability that might be expected in a glaucomatous eye, are also classified by the network to establish the extent of noise upon classification. Field change is then measured with respect to classification of a subsequent field, outside the area defined by the original field and its variants. The significant contribution of this paper is that the spatial analysis of the field data, which is provided by the SOM, has been augmented with noise analysis enhancing the visual representation of longitudinal data and enabling quantification of significant class change.

背景与目标： 本文报道了人工神经网络在眼科数据临床分析中的应用。特别是，二维Kohonen自组织特征图（SOM）用于分析来自青光眼患者的视野数据。重要的是，本文解决了如何利用SOM来容纳数据中的噪声的问题。这在纵向评估中是一个特别重要的问题，在纵向评估中，检测到重大变化是临床诊断中问题的症结所在。来自737青光眼视野记录（汉弗莱视野分析仪，程序24-2）的数据用于训练SOM，并在一个正方形网格上组织25个节点。 SOM对组织输出图的数据进行聚类，以使具有早期和晚期损失的字段处于极端位置，并且中间节点代表的损失位置和程度的连续变化。对于每个SOM节点100，通过计算机模拟生成的变量也可以通过网络进行分类，以建立分类后的噪声范围，这些变量是在青光眼中可能预期的可变性建模而成的。然后根据原始字段及其变体定义的区域之外的后续字段的分类，测量字段变化。本文的重要贡献在于，由SOM提供的现场数据的空间分析已通过噪声分析得到了增强，从而增强了纵向数据的可视化表示并能够量化重大的类别变化。

BACKGROUND & AIMS: :Atomoxetine improves inhibitory control and visual processing in healthy volunteers and adults with attention-deficit/hyperactivity disorder (ADHD). However, little is known about the neural correlates of these two functions after chronic treatment with atomoxetine. This study aimed to use the counting Stroop task with functional magnetic resonance imaging (fMRI) and the Cambridge Neuropsychological Test Automated Battery (CANTAB) to investigate the changes related to inhibitory control and visual processing in adults with ADHD. This study is an 8-week, placebo-controlled, double-blind, randomized clinical trial of atomoxetine in 24 drug-naïve adults with ADHD. We investigated the changes of treatment with atomoxetine compared to placebo-treated counterparts using the counting Stroop fMRI and two CANTAB tests: rapid visual information processing (RVP) for inhibitory control and delayed matching to sample (DMS) for visual processing. Atomoxetine decreased activations in the right inferior frontal gyrus and anterior cingulate cortex, which were correlated with the improvement in inhibitory control assessed by the RVP. Also, atomoxetine increased activation in the left precuneus, which was correlated with the improvement in the mean latency of correct responses assessed by the DMS. Moreover, anterior cingulate activation in the pre-treatment was able to predict the improvements of clinical symptoms. Treatment with atomoxetine may improve inhibitory control to suppress interference and may enhance the visual processing to process numbers. In addition, the anterior cingulate cortex might play an important role as a biological marker for the treatment effectiveness of atomoxetine. Hum Brain Mapp 38:4850-4864, 2017. © 2017 Wiley Periodicals, Inc.

背景与目标： ：Atomoxetine可改善健康志愿者和患有注意力不足/多动症（ADHD）的成年人的抑制性控制和视觉处理。然而，关于用阿托西汀长期治疗后这两种功能的神经相关性知之甚少。这项研究旨在利用功能性磁共振成像（fMRI）和剑桥神经心理测试自动电池（CANTAB）的计数Stroop任务来研究与ADHD成人抑制控制和视觉处理有关的变化。这项研究是一项为期8周，安慰剂对照，双盲，随机的阿托西汀临床试验，该试验在24名未接受过药物治疗的ADHD成人中进行。我们使用计数Stroop fMRI和两项CANTAB测试研究了与安慰剂治疗的对等药物相比，阿托莫西汀治疗的变化：两种方法进行快速视觉信息处理（RVP）进行抑制控制，对样品进行延迟匹配（DMS）进行视觉处理。 Atomoxetine减少了右下额回和前扣带回皮层的激活，这与RVP评估的抑制控制的改善有关。同样，阿托西汀增加了左前胎的激活，这与DMS评估的正确反应的平均潜伏期的改善相关。此外，在治疗前扣带回激活能够预测临床症状的改善。用阿托西汀治疗可以改善抑制控制以抑制干扰，并可以增强视觉处理能力。此外，前扣带回皮质可能作为阿莫西汀治疗效果的生物学标志物发挥重要作用。嗡嗡声大脑Mapp 38：4850-4864，2017.©2017 Wiley Periodicals，Inc.

BACKGROUND & AIMS: :Suramin is a polyanionic compound currently used under evaluation for antineoplastic activity. One of the main problems encountered during clinical trials was an adverse neurotoxic effect, probably due to a direct cytotoxic effect on neural cells. Suramin is also known to trigger differentiation of human colon cancer cells, yet a chronic treatment induces a lysosomal storage disorder. The aim of this study was to evaluate suramin analogs for their effect: (i) on the lysosomal system of the human colon cancer cell clone HT29-D4; and (ii) on C6 glioma cell growth and morphology. One of the derivatives tested, NF036, induced terminal differentiation of HT29-D4 cells without any impairment of the lysosomal system. Furthermore, in contrast to suramin, NF036 did not alter C6 cell growth and morphology. We conclude that there is a relationship between the ability of a suramin derivative to induce a lysosomal storage disorder in human colon cancer cells and its neurotoxic effect. A double screening of suramin analogs on HT29-D4 and C6 cells allowed us to identify a new candidate antineoplastic drug: NF036.

背景与目标： ：Suramin是目前正在评估抗肿瘤活性的聚阴离子化合物。临床试验期间遇到的主要问题之一是不良的神经毒性作用，这可能是由于对神经细胞的直接细胞毒性作用所致。还已知苏拉明会触发人结肠癌细胞的分化，然而长期治疗会引起溶酶体贮积症。这项研究的目的是评估苏拉明类似物的作用：（i）对人结肠癌细胞克隆HT29-D4的溶酶体系统； （ii）C6胶质瘤细胞的生长和形态。测试的衍生物之一NF036诱导了HT29-D4细胞的终末分化，而对溶酶体系统没有任何损害。此外，与苏拉明相反，NF036不会改变C6细胞的生长和形态。我们得出结论，苏拉明衍生物在人结肠癌细胞中诱导溶酶体贮积病的能力与其神经毒性作用之间存在关联。在HT29-D4和C6细胞上对苏拉明类似物的双重筛选使我们能够鉴定出新的候选抗肿瘤药NF036。

BACKGROUND & AIMS: :Memory formation is hypothesized to involve the generation of event-specific neural activity patterns during learning and the subsequent spontaneous reactivation of these patterns. Here, we present evidence that these processes can also be observed in urethane-anesthetized rats and are enhanced by desynchronized brain state evoked by tail pinch, subcortical carbachol infusion, or systemic amphetamine administration. During desynchronization, we found that repeated tactile or auditory stimulation evoked unique sequential patterns of neural firing in somatosensory and auditory cortex and that these patterns then reoccurred during subsequent spontaneous activity, similar to what we have observed in awake animals. Furthermore, the formation of these patterns was blocked by an NMDA receptor antagonist, suggesting that the phenomenon depends on synaptic plasticity. These results suggest that anesthetized animals with a desynchronized brain state could serve as a convenient model for studying stimulus-induced plasticity to improve our understanding of memory formation and replay in the brain.

背景与目标： 假设记忆形成涉及学习过程中事件特定的神经活动模式的产生以及这些模式的随后自发激活。在这里，我们提供的证据表明，这些过程也可以在氨基甲酸乙酯麻醉的大鼠中观察到，并因尾巴捏合，皮层下卡巴胆碱输注或全身苯丙胺给药引起的失调的大脑状态而得到增强。在去同步期间，我们发现反复的触觉或听觉刺激在体感和听觉皮层中引起了神经放电的独特顺序模式，然后这些模式在随后的自发活动中再次发生，类似于我们在清醒动物中观察到的情况。此外，NMDA受体拮抗剂阻止了这些模式的形成，表明该现象取决于突触可塑性。这些结果表明，具有失步的大脑状态的麻醉动物可以作为研究刺激诱导的可塑性的便捷模型，以增进我们对大脑记忆形成和重放的理解。

BACKGROUND & AIMS: :Recent studies have shown important roles for autophagy genes in the regulation of different tissue stem cells, including neural stem/progenitor cells (NSCs). However, little is known about whether autophagy can regulate NSCs through cell-extrinsic mechanisms. Here, we show that deletion of an essential autophagy gene, FIP200, in NSCs increased expression of Ccl5 and Cxcl10 in a p53-independent manner, mediating increased infiltration of microglia into the subventricular zone of both FIP200hGFAP conditional knockout (cKO) and FIP200;p53hGFAP 2cKO mice. The microglia exhibited an activated M1 phenotype consistent with their potential to inhibit differentiation of FIP200-null NSCs. Blocking either microglia infiltration or activation rescued the deficient differentiation of FIP200-null NSCs from FIP200;p53hGFAP 2cKO mice. Lastly, we showed that increased chemokine expression in FIP200-null NSCs was induced by abnormal p62 aggregate formation and activation of NF-κB signaling. Our results suggest that autophagy plays a crucial role in regulating neurogenesis and restricting local immune response in postnatal NSCs through non-cell autonomous mechanisms.

背景与目标： ：最近的研究表明自噬基因在调节不同组织干细胞（包括神经干/祖细胞（NSC））中的重要作用。然而，关于自噬是否可以通过细胞外源性机制调节NSC的了解甚少。在这里，我们显示出在NSC中缺失必不可少的自噬基因FIP200以不依赖p53的方式增加了Ccl5和Cxcl10的表达，介导了小胶质细胞浸润入FIP200hGFAP条件性基因敲除（cKO）和FIP200; p53hGFAP的脑室下区域2cKO小鼠。小胶质细胞表现出活化的M1表型，与其抑制FIP200无效的NSCs分化的潜力一致。阻断小胶质细胞浸润或激活可以从FIP200; p53hGFAP 2cKO小鼠中拯救FIP200-null NSC的不足分化。最后，我们表明，FIP200-null NSCs中趋化因子表达的增加是由异常的p62聚集体形成和NF-κB信号传导引起的。我们的结果表明自噬在调节神经发生和通过非细胞自主机制限制产后NSC中的局部免疫反应中起着至关重要的作用。

BACKGROUND & AIMS: :The post-ictal immobility syndrome is followed by a significant increase in the nociceptive thresholds in animals and men. In this interesting post-ictal behavioral response, endogenous opioid peptides-mediated mechanisms, as well as cholinergic-mediated antinociceptive processes, have been suggested. However, considering that many serotonergic descending pathways have been implicated in antinociceptive reactions, the aim of the present work is to investigate the involvement of 5-HT(2)-serotonergic receptor subfamily in the post-ictal antinociception. The analgesia was measured by the tail-flick test in seven or eight Wistar rats per group. Convulsions were followed by statistically significant increase in the tail-flick latencies (TFL), at least for 120 min of the post-ictal period. Male Wistar rats were submitted to stereotaxic surgery for introduction of a guide-cannula in the rhombencephalon, aiming either the nucleus raphe magnus (NRM) or the gigantocellularis complex. In independent groups of animals, these nuclei were neurochemically lesioned with a unilateral microinjection of ibotenic acid (1.0 microg/0.2 microL). The neuronal damage of either the NRM or nucleus reticularis gigantocellularis/paragigantocellularis complex decreased the post-ictal analgesia. Also, in other independent groups, central administration of ritanserin (5.0 microg/0.2 microL) or physiological saline into each of the reticular formation nuclei studied caused a statistically significant decrease in the TFL of seizing animals, as compared to controls, in all post-ictal periods studied. These results indicate that serotonin input-connected neurons of the pontine and medullarly reticular nuclei may be involved in the post-ictal analgesia.

背景与目标： ：发作后固定不动综合症之后，动物和男性的伤害感受性阈值显着增加。在这种有趣的发作后行为反应中，已经提出了内源性阿片肽介导的机制以及胆碱能介导的抗伤害感受过程。但是，考虑到许多血清素能下降途径已与抗伤害感受性反应有关，因此本研究的目的是研究5-HT（2）-5-羟色胺能受体亚家族在发作后抗伤害感受中的作用。通过甩尾试验在每组七或八只Wistar大鼠中测量镇痛作用。抽搐后，甩尾潜伏期（TFL）至少在发作后的120分钟内有统计学上的显着增加。将雄性Wistar大鼠接受立体定向手术，以在菱形脑中引入引导套管，以引导中缝大核（NRM）或大细胞复合体。在独立的动物组中，通过单侧显微注射异丁烯酸（1.0微克/0.2微升）对这些细胞核进行神经化学损伤。 NRM或网状巨大巨细胞/副巨干细胞复合物的神经元损伤减少了发作后镇痛作用。此外，在其他独立组中，与对照组相比，在所有给药后的研究中，将利坦色林（5.0微克/0.2微升）或生理盐水集中施用到所研究的每个网状结构核中均导致了癫痫发作动物的TFL值在统计学上显着下降。最重要的时期。这些结果表明桥脑和髓质网状核的5-羟色胺输入连接神经元可能参与了发作后镇痛。

BACKGROUND & AIMS: :The aim of this study was to determine the brain structures as well as the plasticity events associated with the behavioral effects of cholinergic damage. Rats were submitted to injection of 192 IgG-saporin in the medial septum/diagonal band of Broca complex and the nucleus basalis magnocellularis. The immunohistochemical expression of c-Fos protein and PSA-NCAM (polysialylated neural cell adhesion molecule) and the behavioral performances in the nonmatching-to-position task were assessed at various post-lesion times. Thus, 3 days after injection of the immunotoxin, increased c-Fos labeling was observed in the areas of infusion, indicating these cells were undergoing some plastic changes and/or apoptotic processes. A drastic increase was observed in the number of PSA-NCAM positive cells and in their dendritic arborization in the dentate gyrus. At 7 days post-lesion, no behavioral deficit was observed in immunolesioned rats despite the drastic loss of cholinergic neurons. These neurons showed decreased c-Fos protein expression in the piriform and entorhinal cortex and in the dentate gyrus. In the latter, PSA-NCAM induction was high, suggesting that remodeling occurred, which in turn might contribute to sustaining some mnemonic function in immunolesioned rats. At 1 month, cholinergic neurons totally disappeared and behavioral deficits were drastic. c-Fos expression showed no change. In contrast, the increased PSA-NCAM-labeling observed at short post-lesion times was maintained but the plastic changes due to this molecule could not compensate the behavioral deficit caused by the immunotoxin. Thus, as the post-lesion time increases, a gradual degeneration process should occur that may contribute to mnemonic impairments. This neuronal loss leads to molecular and cellular alterations, which in turn may aggravate cognitive deficits.

背景与目标： ：这项研究的目的是确定与胆碱能损害的行为影响有关的大脑结构以及可塑性事件。大鼠在Broca复合体和大细胞基底核的中隔/对角带内注射192种IgG-saporin。在损伤后的各个时间评估c-Fos蛋白和PSA-NCAM（多唾液酸化神经细胞粘附分子）的免疫组织化学表达以及在不匹配位置任务中的行为表现。因此，在注射免疫毒素后三天，在输注区域观察到c-Fos标记增加，表明这些细胞正在经历一些塑性变化和/或凋亡过程。观察到PSA-NCAM阳性细胞的数量及其在齿状回中的树突状乔化急剧增加。在损伤后7天，尽管胆碱能神经元急剧丧失，但在免疫损伤大鼠中未观察到行为缺陷。这些神经元在梨状和内嗅皮层以及齿状回中显示出降低的c-Fos蛋白表达。在后者中，PSA-NCAM诱导较高，表明发生了重塑，这反过来可能有助于维持免疫受损大鼠的某些记忆功能。 1个月时，胆碱能神经元完全消失，行为缺陷严重。 c-Fos表达无变化。相反，在损伤后短时间内观察到的PSA-NCAM标记增加得以维持，但由于该分子引起的塑性变化无法弥补免疫毒素引起的行为缺陷。因此，随着损伤后时间的增加，应该发生逐渐退化的过程，这可能会导致记忆障碍。这种神经元的丧失导致分子和细胞的改变，继而可能加剧认知缺陷。

BACKGROUND & AIMS: :The neurokinin Substance P (SP) is widely distributed in the central nervous system and has been extensively studied in various functional aspects. This review focuses on the behavioral relevance of SP. Here we show that SP can have memory-promoting, reinforcing and anxiolytic-like effects when administered systemically or into the nucleus basalis of the ventral pallidum. These effects seem to be mediated via the SP-preferring NK(1)receptor and differentially related to N- versus C-terminal fragments of the undecapeptide. Secondly, SP injection into the ventral pallidum can lead to increases of acetylcholine in frontal cortex and dopamine in nucleus accumbens, suggesting that the hypermnestic, positively reinforcing and anxiolytic effects observed upon basal forebrain injection of SP are mediated by activation of the nucleus accumbens-ventral pallidum circuitry. Furthermore, SP and certain SP-fragments may not only be considered to have beneficial behavioral effects in normal animals, but can also prevent lesion-induced functional deficits and improve the speed of recovery. This indicates that SP agonists might also have a neuroprotective capacity in parallel with recovery-promoting actions.

背景与目标： ：神经激肽P（SP）广泛分布于中枢神经系统，并已在各个功能方面进行了广泛研究。这篇综述着重于SP的行为相关性。在这里我们表明，当全身或腹侧苍白球的核基底层给药时，SP可以具有促进记忆，增强和抗焦虑的作用。这些作用似乎是通过SP优先的NK（1）受体介导的，并且与十一肽的N端和C端片段差异相关。其次，向腹侧苍白球注射SP可导致额叶皮层中的乙酰胆碱和伏隔核中的多巴胺增加，这表明SP前基底脑注入的高记忆力，正增强和抗焦虑作用是由伏隔核-腹膜的激活介导的。苍白的电路。此外，SP和某些SP片段不仅可以被认为在正常动物中具有有益的行为效果，而且还可以防止病变引起的功能缺陷并提高恢复速度。这表明SP激动剂可能还具有促进恢复作用的神经保护能力。

BACKGROUND & AIMS: OBJECTIVE:The aim of this study was to review cases of neural tube defect with special focus on presentation, epidemiology and clinical presentation. Management with complications and results of surgery were discussed. METHODS:Ninety-three cases, born with neural tube defect (spina bifida aperta) were operated upon in our unit at King Hussein Medical Centre, Amman, Jordan, from June 1997 to October 2000. Data was retrospectively reviewed and analyzed. RESULTS:Major neurological deficits were present in 28 cases (complete loss of function below the level of the lesion) and 19 cases were intact. Lesion size was less than 3.5 cm in 72 cases (77.4%); 3.5-7.5 cm in 15 cases (16.1%) and 6 cases were more than 7.5 cm. Seventy-two cases had an intact lesion before surgery while the other 21 cases ruptured either during delivery or soon later. For the site of lesion, 51 cases were lumbar, 22 cases were lumbosacral, 13 cases were thoracolumbar, 4 cases were thoracic and 3 cases were cervical. Early surgery was carried out for all cases, primary closure was possible in all cases. Nineteen cases had post-operative complications, wound infection (superficial) 6 cases (7%), leakage of cerebrospinal fluid 5 cases (5%), meningitis 3 cases (3%), skin necrosis 3 cases (3%) and 2 deaths. CONCLUSION:Jordan has a large number of born spina bifida cases, as the practice of pregnancy termination is socially and religiously unacceptable. Our approach to management, is to repair all intact patients. For patients with major neurological deficits we advise the family on the natural history of the disease and postoperative status of the patient leaving the decision to the family. The presentation was similar to that described in literature.

背景与目标： 目的：本研究旨在回顾神经管缺损的病例，特别侧重于表现，流行病学和临床表现。讨论了并发症的处理和手术结果。
方法：1997年6月至2000年10月，在约旦安曼国王侯赛因医学中心对我科收治的93例神经管缺损（脊柱裂）患者进行了手术。对数据进行回顾性分析。
结果：28例患者存在严重的神经功能缺损（在病变水平以下完全丧失功能），完整者19例。 72例病灶小于3.5cm（占77.4％）； 3.5厘米至7.5厘米的病例中有15例（占16.1％），超过7.5厘米的有6例。手术前有72例病灶完整，而其他21例在分娩时或不久后破裂。病变部位：腰51例，腰ac22例，胸腰13例，胸4例，颈3例。所有病例均进行了早期手术，所有病例均可能进行初次闭合。术后并发症19例，伤口感染（浅表）6例（7％），脑脊液漏5例（5％），脑膜炎3例（3％），皮肤坏死3例（3％），2例死亡。
结论：约旦有大量出生的脊柱裂病例，因为终止妊娠的做法在社会和宗教上都是不可接受的。我们的管理方法是修复所有完整的患者。对于有严重神经功能缺损的患者，我们建议其自然疾病史和患者的术后状况告知家人，并由家人决定。该介绍与文献中描述的类似。