艾司西酞普兰与舍曲林治疗老年脑卒中后抑郁对照研究

目的：探讨艾司西酞普兰与舍曲林治疗老年脑卒中后抑郁患者的临床疗效和安全性。方法将80例老年脑卒中后抑郁患者随机分为两组,均予以神经内科常规治疗及康复治疗,在此基础上研究组口服艾司西酞普兰治疗,对照组口服舍曲林治疗,观察8周。治疗前后采用汉密顿抑郁量表评定临床疗效,副反应量表评定不良反应。结果研究组治疗第1周末汉密顿抑郁量表总分较对照组下降更显著（ P＜0．01）,治疗第8周末研究组显效率80．0％、有效率92．5％,对照组分别为70．0％、90．0％,两组比较差异均无显著性（ P＞0．05）。两组不良反应较轻微,但研究组口干、腹泻不良反应发生率显著低于对照组（P＜0．01）。结论艾司西酞普兰治疗老年脑卒中后抑郁的疗效显著,与舍曲林相当,但艾司西酞普兰起效更快,安全性更高,更适合老年脑卒中后抑郁患者。     

Course and predictors of medically unexplained pain symptoms in the general population

OBJECTIVE: The objective of this study was to explore the course and the predictors of clinically significant medically unexplained pain symptoms (MUS-pain) within the 6 months preceding the interviews at baseline and on follow-up in the general population. METHODS: A Norwegian general population study of 605 persons interviewed with the Composite International Diagnostic Interview Somatoform Section was conducted in 1989/1990 (baseline), and 421 persons (69.6% response rate; 242 women and 179 men) were reinterviewed in 2000/2001 (follow-up). Cases of recent MUS-pain compared with those at baseline were assessed on follow-up. Four blockwise logistic regression analyses were undertaken to find predictors (such as stressful life events, living alone, depression and anxiety, and physical morbidity) for recent MUS-pain in 2001. RESULTS: A small "stable" group of recent MUS-pain sufferers (8% of all reinterviewed and 33.6% of those with recent MUS-pain at baseline) was evident. In this group almost all were women. In addition to female gender being a significant (P<.05) marker of recent MUS-pain (which gives a twofold-higher risk compared with men), only depression--not the occurrence of prior recent MUS-pain--remained a significant (P<.05) predictor in the final model, increasing the likelihood of having recent MUS-pain by threefold. CONCLUSION: The prognosis of MUS-pain is relatively good, except for a small group (mainly women) that is prone to chronicity. Clinicians should examine for depression when confronted with MUS-pain patients and should be aware of the twofold-higher risk in women for persistent MUS-pain over a long time.     

Influence of the NR3A subunit on NMDA receptor functions

Various combinations of subunits assemble to form the NMDA-type glutamate receptor (NMDAR), generating diversity in its functions. Here we review roles of the unique NMDAR subunit, NR3A, which acts in a dominant-negative manner to suppress receptor activity. NR3A-containing NMDARs display striking regional and temporal expression specificity, and, unlike most other NMDAR subtypes, they have a low conductance, are only modestly permeable to Ca²⁺, and pass current at hyperpolarized potentials in the presence of magnesium. While glutamate activates triheteromeric NMDARs composed of NR1/NR2/NR3A subunits, glycine is sufficient to activate diheteromeric NR1/NR3A-containing receptors. NR3A dysfunction may contribute to neurological disorders involving NMDARs, and the subunit offers an attractive therapeutic target given its distinct pharmacological and structural properties.     

卒中后抑郁心理护理的临床观察

卒中后抑郁是卒中患者最常见的心理障碍,发挥中医心理治疗与护理的优势,加强对PSD患者的情志调护,使其早日进入躯体、心理康复的良性循环,显得尤为重要,对PSD患者进行中医情志护理,具有重要的临床治疗价值。     

Innervation of orexin/hypocretin neurons by GABAergic, glutamatergic or cholinergic basal forebrain terminals evidenced by immunostaining for presynaptic vesicular transporter and postsynaptic scaffolding proteins

Orexin/hypocretin (Orx) neurons are critical for the maintenance of waking in association with behavioral arousal and postural muscle tone, since with their loss narcolepsy with cataplexy occurs. Given that basal forebrain (BF) neurons project to the hypothalamus and play important diverse roles in sleep/wake states, we sought to determine whether acetylcholine (ACh), glutamate (Glu), and/or GABA-releasing BF neurons innervate and could thereby differentially regulate the Orx neurons. From discrete injections of biotinylated dextran amine (BDA, 10,000 MW) into the magnocellular preoptic nucleus (MCPO) and substantia innominata (SI) in the rat, BDA-labeled fibers projected to the lateral hypothalamus (LH), perifornical area (PF), and dorsomedial hypothalamus (DMH), where approximately 41%, approximately 11%, and 9% of Orx-positive (+) neurons were respectively contacted in each region. Employing triple fluorescent staining for Orx, BDA, and presynaptic vesicular (V) transporters (T), we found that only 4% of the innervated Orx+ neurons in the LH were contacted by BDA+[VAChT+] terminals, whereas approximately 31% and approximately 67% were respectively contacted by BDA+[VGluT2+] and BDA+[VGAT+] terminals. In 3D-rendered and rotated confocal images, we confirmed the latter contacts and examined staining for postsynaptic proteins PSD-95, a marker for glutamatergic synapses, and gephyrin, a marker for GABAergic synapses, that were located on Orx+ neurons facing BDA-labeled terminals in approximately 20% and approximately 50% of contacts, respectively. With such synaptic input, BF glutamatergic neurons can excite Orx neurons and thus act to maintain behavioral arousal with muscle tone, whereas GABAergic neurons can inhibit Orx neurons and thus promote behavioral quiescence and sleep along with muscle atonia.     

Noise reduction based on ICA decomposition and wavelet transform for the extraction of motor unit action potentials

We have studied methods for noise reduction of myoelectric signals and for extraction of motor unit action potentials from these signals. Effective MUAP peak detection is the first important step in EMG decomposition. We first combined independent component analysis and wavelet filtering to remove power line interference, and then applied a wavelet filtering method and threshold estimation calculated using wavelet transform to suppress background noise and Gaussian white noise. The technique was applied to single-channel, short-period real myoelectric signals from normal subjects and to artificially generated EMG recordings. In contrast to existing methods based on amplitude single-threshold filtering of the original myoelectric signal or a conventional digitally filtered signal, our technique is fast and robust. Moreover, the proposed algorithm is substantially automatic. The performance has been evaluated with a set of synthetic and experimentally recorded myoelectric signals. The basic tool for testing was power spectrum density (PSD) estimation by the Welch method, which allowed us to analyze the PSD of nonstationary signals.     

Gender differences in response of hippocampus to chronic glucocorticoid stress: role of glutamate receptors

Glucocorticoids (GC) play critical roles in the pathophysiological reactions to environmental stress. In brain, morphological changes were examined in hippocampal CA3 neurons with 2 weeks of chronic elevation of GC in male and female mice. Molecular correlates and underlying mechanisms paralleling these morphologic changes in hippocampus were investigated. Although the hippocampal neurons in the CA3 area in male mice atrophy with chronically elevated GC, female mice show minimal morphological changes with comparable GC regimens. These sexual morphological differences correlate with differences in the postsynaptic dense protein (PSD95) as well as the spectrum of glutamate receptors induced by GC treatment in male and female mice, including NMDA, AMPA, and KA receptors. These findings suggest that synaptic receptor composition is adapted to the unique physiological requirements of males and females and illuminate underlying mechanisms of GC/stress responses in the brain.     

Characterization of developing rat cortical neurons after epileptiform discharges

The developing brain undergoes major reorganization in response to early environmental changes. The elevated excitation that allows the neonatal brain to develop quickly also makes it highly vulnerable to age-specific seizures that can cause lifelong cognitive and neurological disability. However, it is not yet clear how seizures interfere with the developmental program and how epileptogenesis actualize. Here, by using an in vitro model, we report a global abnormal status of cortical cells after epileptiform activity was induced: more NR2B is targeted on the neuronal surface with less NR2A. Dendrotoxicity including dendritic beading, distortion and simplification of dendritic branching patterns were observed. Early-life seizure-like insults also exert effects on the excitatory synaptic size and interactions between PSD-95 and NR2A or NR2B receptor subunits. Our findings support an abnormal development or, worse, cellular degeneration that resembles immature cells, which may enlighten better understanding of the pathological mechanism of early-life seizures and its related injury.     

Time dependent subthalamic local field potential changes after DBS surgery in Parkinson's disease

Local field potentials (LFPs) recorded through electrodes implanted in patients with Parkinson's disease (PD) for deep brain stimulation (DBS) provided physiological information about the human basal ganglia. However, LFPs were always recorded 2–7 days after electrode implantation (“acute” condition). Because changes in the tissue surrounding the electrode occur after DBS surgery and could be relevant for LFPs, in this work we assessed whether impedance and LFP pattern are a function of the time interval between the electrode implant and the recordings. LFPs and impedances were recorded from 11 patients with PD immediately after (T-0h), 2 h after (T-2h), 2 days after (T-48h), and 1 month after (T-30d, “chronic” condition) surgery. Impedances at T-0h were significantly higher than at all the other time intervals (T-2h, p = 0.0005; T-48h, p = 0.0002; T-30d, p = 0.003). Correlated with this change (p = 0.005), the low-frequency band (2-7 Hz) decreased at all time intervals (p = 0.0005). Conversely, the low- (8–20 Hz) and the high-beta (21–35 Hz) bands increased in time (low-beta, p = 0.003; high beta, p = 0.022), but did not change between T-48h and T-30d. Our results suggest that DBS electrode impedance and LFP pattern are a function of the time interval between electrode implant and LFP recordings. Impedance decrease could be related to changes in the electrode/tissue interface and in the low-frequency band. Conversely, beta band modulations could raise from the adaptation of the neural circuit. These findings confirm that results from LFP analysis in the acute condition can be extended to the chronic condition and that LFPs can be used in novel closed-loop DBS systems.     

Hepatocyte growth factor improves synaptic localization of the NMDA receptor and intracellular signaling after excitotoxic injury in cultured hippocampal neurons

To examine the effects of HGF on synaptic densities under excitotoxic conditions, we investigated changes in the number of puncta detected by double immunostaining with NMDA receptor subunits and presynaptic markers in cultured hippocampal neurons. Exposure of hippocampal neurons to excitotoxic NMDA (100 muM) decreased the synaptic localization of NMDA receptor subunit NR2B, whereas synaptic NR1 and NR2A clusters were not altered. Colocalization of PSD-95, a scaffolding protein of the receptor, with the presynaptic protein synapsin I was also decreased after excitotoxicity. Treatment with HGF attenuated these decreases in number. The decrease in the levels of surface NR2B subunits following the addition of the excitotoxic NMDA was also attenuated by the HGF treatment. The decrease in CREB phosphorylation in response to depolarization-evoked NMDA receptor activation was prevented by the HGF treatment. These results suggest that HGF not only prevented neuronal cell death but also attenuated the decrease in synaptic localization of NMDA receptor subunits and prevented intracellular signaling through the NMDA receptor.