脑卒中后抑郁的发生率与危险因素的研究

目的:调查脑卒中患者抑郁的发生率,分析影响脑卒中后抑郁(post-stroke depression,PSD)发生率的相关因素。方法:随机调查400例符合纳入标准的脑卒中后的患者,采用自行设计的基本资料调查表收集患者的一般资料,采用抑郁自评量表(SDS)和汉密尔顿抑郁量表(HAMD)17项版本评定患者的抑郁情况,采用Barthel生活能力指数(B1)对患者日常生活能力评分,采用改良的爱丁堡斯堪的那维亚神经功能缺损评分表(SSS)对神经功能缺损评分(NFA)。结果:PSD总发生率为49.5%,其中轻度抑郁为26.5%,中度抑郁为16.0%,重度抑郁为7.0%,影响脑卒中后抑郁发生的相关因素有既往抑郁病史(P=0.000)、性别(P=0.046)、社会交往(P=0.000)、家庭关系(P=0.000)、照料人(P=0.000)、既往患病(P=0.000)、合并疾病种类(P=0.000)、卒中后病程(P=0.000)、日常生活能力(P=0.000)和神经功能缺损(P=0.000)。结论:脑卒中后抑郁的发生可能是多种因素共同作用的结果。     

Synaptogenesis: a balancing act between excitation and inhibition

Recent studies have implicated a number of membrane-associated proteins, including the signaling pair neuroligin and beta-neurexin, in synapse formation, suggesting that they govern the ratio of inhibitory and excitatory synapses on CNS neurons. These findings, together with data indicating that the genes encoding neuroligin and PSD95 are altered in autism patients, suggest that a molecular understanding of complex neurological diseases is within reach.     

Factors determining post-stimulation dilatation

Post-stimulation dilatation (PSD) of the femoral artery and vein after cessation of postganglionic sympathetic stimulation were related to the frequency and pulse number of the preceding stimulation. It was found that: 1) A minimum number of pulses (MNP) is needed to evoke PSD. MNP is inversely related to the stimulation frequency. A marked PSD develops after stimulation at 1 Hz when only 100 pulses were applied, whereas, if stimulated at 4 Hz or at higher frequencies, even 2,000 pulses fail to induce PSD. 2) The maximum value, the maximum rate and the overall diameter change of PSD (expressed either in absolute values or in relation to the preceding contraction) are a) directly related to the number of pulses at a constant stimulation frequency, b) for a constant number of pulses the above values are inversely related to the stimulation frequency. 3) The relation of PSD values to the stimulation parameters contradict the assumption that PSD is elicited either by a neurogenic transmitter released by the stimulation, or by an extraneuronal transmitter whose release is associated with the release of noradrenaline. PSD is suggested to be due to a decreased noradrenaline level within the synaptic cleft due to persistence of the reuptake after the release of noradrenaline had ceased.     

Scaffolding Proteins of the Post-synaptic Density Contribute to Synaptic Plasticity by Regulating Receptor Localization and Distribution: Relevance for Neuropsychiatric Diseases

Synaptic plasticity represents the long lasting activity-related strengthening or weakening of synaptic transmission, whose well-characterized types are the long term potentiation and depression. Despite this classical definition, however, the molecular mechanisms by which synaptic plasticity may occur appear to be extremely complex and various. The post-synaptic density (PSD) of glutamatergic synapses is a major site for synaptic plasticity processes and alterations of PSD members have been recently implicated in neuropsychiatric diseases where an impairment of synaptic plasticity has also been reported. Among PSD members, scaffolding proteins have been demonstrated to bridge surface receptors with their intracellular effectors and to regulate receptors distribution and localization both at surface membranes and within the PSD. This review will focus on the molecular physiology and pathophysiology of synaptic plasticity processes, which are tuned by scaffolding PSD proteins and their close related partners, through the modulation of receptor localization and distribution at post-synaptic sites. We suggest that, by regulating both the compartmentalization of receptors along surface membrane and their degradation as well as by modulating receptor trafficking into the PSD, postsynaptic scaffolding proteins may contribute to form distinct signaling micro-domains, whose efficacy in transmitting synaptic signals depends on the dynamic stability of the scaffold, which in turn is provided by relative amounts and post-translational modifications of scaffolding members. The putative relevance for neuropsychiatric diseases and possible pathophysiological mechanisms are discussed in the last part of this work.     

Down-expressed GLT-1 in PSD astrocytes inhibits synaptic formation of NSC-derived neurons in vitro

Little is known about the effect of astroglial GLT-1 of post-stroke depression (PSD) rat model on the function of neural stem cells (NSCs). This study aimed to investigate whether astroglial GLT-1 of PSD rats affect differentiation of NSCs from neonatal rat hippocampus and synaptic formation of NSC-derived neurons. Astrocytes were isolated from the left hippocampus of normal adult SD rats and PSD rats. A lentiviral vector was used to silence the expression of GLT-1 in astrocytes of PSD rats. NSCs were respectively co-cultured with normal (control), PSD, and GLT-1 silenced astrocytes for 7 days. GLT-1, GFAP, MAP2, Synaptophysin (SYN), glutamate (Glu) and glutamine (Gln) were respectively measured by qRT-PCR, western blot, immunofluorescence and efficient mass spectrometry (MS). PSD astrocytes increased the number of NSC-derived astrocytes, but inhibited the expression of GLT-1 of NSC-derived astrocytes and synapses of NSC-derived neurons. On the basis of the low expression of GLT-1 in PSD astrocytes, we further silenced GLT-1 in PSD astrocytes. Interestingly, GLT-1 silenced PSD astrocytes more obviously inhibited synapses of NSC-derived neurons, but increased the number of NSC-derived neurons and reversed the expression of GLT-1 in NSC-derived astrocytes. At the same time, concentration of glutamate in the medium elevated, and glutamine in the medium gradually reduced. In NSC-derived neurons and astrocytes, glutamate metabolism was also affected by changed GLT-1. Down-expressed GLT-1 in PSD astrocytes stimulated NSCs differentiating into astrocytes, but inhibiting the formation of functional synapses by influencing glutamate metabolism in vitro.     

卒中后抑郁与血清炎性细胞因子水平及神经功能损害的相关性分析

目的：探讨急性脑梗死患者不同时间卒中后抑郁（PSD）发病与血清炎性细胞因子水平、神经功能缺损、日常生活能力的相关性。方法：用Hamilton抑郁量表（HDRS）筛查280例符合条件的急性脑梗死患者急性期与恢复期PSD的发病情况,并同时测定血清炎性细胞因子hs-CRP、TNF-α、IL-6的水平,NIHSS评分进行神经功能缺损评估,Barthel指数进行日常生活能力的评估,分析PSD的发生与各因素之间的相关性,采用多因素logistic回归分析进行危险因素分析。结果：脑梗死恢复期PSD的发病率高于急性期,但无明显差异。急性期PSD组血清炎性细胞因子水平高于非PSD组,有显著性差异,而急性期、恢复期神经功能缺损和日常生活能力与非PSD组比较均有显著性差异;急性期血清TNF-α、IL-6和Barthel指数,恢复期NIHSS评分、Barthel指数与PSD发生的OR值分别1.765、1.646、1.817、1.188、2.015。结论：PSD的发病机制在病程的不同时间可能存在着差异,急性期血清升高的炎性细胞因子水平和降低的日常生活能力,恢复期神经功能缺损的程度和降低的日常生活能力是不同时间PSD发病的危险因素。     

血清5-HT、Obestatin、APRIL与老年脑卒中患者神经功能的相关性及对卒中后抑郁的预测价值

摘要 目的：探讨血清5-羟色胺（5-HT）、肥胖抑制素（Obestatin）、增殖诱导配体（APRIL）与老年脑卒中患者神经功能的相关性及对卒中后抑郁（PSD）的预测价值。方法：选择2019年5月至2022年5月内蒙自治区人民医院收治的老年脑卒中患者120例为研究对象。入院时采集血样本,采用酶联免疫吸附法（ELISA）检测血清5-HT、Obestatin和APRIL水平。患者出院后随访6个月,根据是否发生PSD分为PSD组和非PSD组,比较两组血清5-HT、Obestatin、APRIL水平。采用Pearson相关分析法分析5-HT、Obestatin、APRIL与美国国立卫生研究院卒中量表（NIHSS）的相关性;采用多因素Logistic回归模型分析PSD的影响因素;采用受试者工作特征（ROC）曲线分析血清5-HT、Obestatin联合APRIL对老年脑卒中患者出院后PSD的预测价值。结果：PSD组血清5-HT低于非PSD组（P＜0.05）,血清Obestatin、APRIL和NIHSS评分高于非PSD组（P＜0.05）。血清5-HT与NIHSS评分呈负相关（P＜0.05）;血清Obestatin、APRIL与NIHSS评分呈正相关（P＜0.05）。单因素分析显示,老年脑卒中患者出院后PSD与体质量指数（BMI）、吸烟史、饮酒史有关（P＜0.05）。多因素Logistic回归分析显示,血清Obestatin、APRIL及NIHSS评分升高是脑卒中患者出院后发生PSD的危险因素（P＜0.05）,血清5-HT升高是其保护因素（P＜0.05）。ROC曲线分析结果显示,血清5-HT、Obestatin、APRIL及联合检测对预测PSD的曲线下面积（AUC）分别为0.735（0.483～0.978）、0.765（0.595～0.918）、0.707（0.464～0.954）、0.867（0.742～0.972）,联合检测的预测效能优于各指标单独检测。结论：血清5-HT水平降低、Obestatin、APRIL水平及NIHSS评分升高是老年脑卒中患者出院后发生PSD的独立危险因素,还可导致神经功能损伤,血清5-HT、Obestatin和APRIL可预测老年脑卒中患者出院后PSD,且联合预测价值更高。     

Effects of paradoxical sleep deprivation on genital reflexes in five rat strains

This study examined the effects of cocaine on genital reflexes in paradoxical sleep-deprived (PSD) male rats of five strains since it has been demonstrated that this drug enhances genital reflexes in Wistar PSD rats. At the end of a 4-day period of PSD or at the equivalent time-point to control animals, cocaine or saline was acutely administered to the animals and penile erection (PE) and ejaculation (EJ) were quantified. Results indicated that PSD induced genital reflexes in all strains, and cocaine potentiated these behaviors in Wistar and Long-Evans rats. Wistar PSD rats injected with cocaine performed significantly more PE than all the other PSD + cocaine strains. The number of Wistar and Long-Evans PSD + cocaine ejaculating was significantly higher than the respective PSD + saline and control, whereas a tendency of increase was seen in relation to other groups. Wistar PSD + cocaine rats showed the highest EJ frequency compared to F344, Sprague-Dawley and Wistar-Kyoto strains, and the Long-Evans displayed more EJ than Sprague-Dawley and Wistar-Kyoto. Analysis of testosterone concentrations revealed that after sleep deprivation, Wistar, Long-Evans, and F344 rats showed significantly lower testosterone concentrations than control rats. In F344, Sprague-Dawley and Wistar-Kyoto controls rats, testosterone was significantly lower than in the control Wistar and Long-Evans. Progesterone concentrations were significantly higher in Wistar and Long-Evans PSD rats than in respective control groups. In the other strains, this hormone was significantly lower compared to the Wistar and Long-Evans PSD. This study demonstrates that genital reflexes are differently influenced by PSD associated to cocaine in five rat strains.     

Poststroke Depression and Risk of Recurrent Stroke at 1 Year in a Chinese Cohort Study

Background

Studies show that poststroke depression (PSD) increases mortality risk at 1 year. However, whether PSD increases the risk of recurrent stroke at 1 year remains unclear. This study was to investigate whether PSD at 2 weeks following a stroke could increase risk of recurrent stroke at 1 year.

Methods and Results

This was a multi-centered prospective cohort study. A total of 2306 patients with acute stroke were enrolled in our study. PSD was diagnosed according to the criteria set by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). The outcomes of recurrent stroke were followed up via face-to-face or phone interview. A total of 1713 patients had complete follow-up data, with 481 (28.1%) cases of PSD and 158 (9.2%) cases of cumulative recurrent stroke at 1 year. Multivariate logistic regression analysis showed a 49% increase of OR of recurrent stroke at 1 year in patients with PSD, compared to patients without PSD following a stroke (OR = 1.49, 95%CI: 1.03–2.15). There was no significant correlation between anti-depressant drugs and the risk of recurrent stroke at 1 year following a stroke (OR = 1.96, 95%: CI 0.95–4.04).

Conclusions

Based on the DSM-IV diagnostic criteria, nearly 3 out of 10 hospitalized stroke patients in China were diagnosed with PSD at 2 weeks following a stroke. PSD is associated with a higher risk of recurrent stroke at 1 year. Our study did not find benefit of anti-depressant drugs in reducing such risk.     

Application of a novel protein biochip technology for detection and identification of rheumatoid arthritis biomarkers in synovial fluid

We compared protein profiles of the synovial fluid of patients with rheumatoid arthritis and osteoarthritis by using surface-enhanced laser desorption/ionization mass spectrometry technology. With this approach, we identified a protein expressed specifically in the synovial fluid of the patients with rheumatoid arthritis. During the investigation, we found several reproducible and discriminatory biomarker candidates for distinction between rheumatoid arthritis and osteoarthritis. Among these candidates, a 10 850 Da protein peak was the clearest example of a single signal found specifically in the rheumatoid arthritis samples. This candidate was purified using a size-exclusion spin column followed by gel electrophoresis and subsequently identified by peptide mapping and post-source decay (PSD) analysis. The results clearly indicate that the protein is myeloid-related protein 8, which was verified by the enzyme immunoassay. It is known that the myeloid-related protein 8 level in serum and synovial fluid is related to disease activity in juvenile rheumatoid arthritis. The results suggest that the ProteinChip platform is useful to detect and identify protein biomarkers expressed specifically in diseases or in some stage of diseases.     

Coordinate regulation of phosphatidylserine decarboxylase in Saccharomyces cerevisiae.

Regulation of the activity of the mitochondrial enzyme phosphatidylserine decarboxylase (PSD) was measured in vitro by using membrane preparations from wild-type and mutant strains of Saccharomyces cerevisiae. PSD specific activity was not affected by carbon source, and on all carbon sources, the highest specific activity was observed in cells entering the stationary phase of growth. However, PSD activity was found to be regulated in response to soluble precursors of phospholipid biosynthesis. PSD specific activity was reduced to about 63% of the level observed in unsupplemented wild-type cells when the cells were grown in the presence of 75 microM inositol. The presence of 1 mM choline alone had no repressing effect, but the presence of 1 mM choline and 75 microM inositol together led to further repression to a level of about 28% of the derepressed activity. Regulatory mutations known to affect regulation or expression of genes encoding phospholipid-synthesizing enzymes also affected PSD specific activity. opi1 mutants, which are constitutive for a number of phospholipid-biosynthetic enzymes, were found to have high, constitutive levels of PSD. Likewise, in ino2 or ino4 regulatory mutants, PSD activity was found to be at the fully repressed level regardless of growth condition. Regulation of PSD activity was also affected in several structural-gene mutants under conditions of impaired phosphatidylcholine biosynthesis. Together, these data strongly suggest that PSD expression is controlled by the mechanism of general control of phospholipid biosynthesis that regulates many enzymes of phospholipid biosynthesis.     

A Prospective Study of the Incidence and Correlated Factors of Post-Stroke Depression in China

Background

Post-stroke depression (PSD) is commonly observed among stroke survivors. However, statistical analysis of such data is scarce in developing countries. The purpose of this study is to examine the incidence of PSD and its relationship with stroke characteristics in China.

Methods

This was a prospective hospital-based study. Stroke patients were assessed within two weeks after acute ischemic stroke onset and then reevaluated at three months. Hamilton Depression Scale (HAMD) was used for screening depression (PSD). Subjects with HAMD score of ≥7 were further assessed with the World Health Organization Composite International Diagnostic Interview. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIHSS). Stroke outcome was measured by the modified Rankin Scale (mRS).

Results

One hundred and two stroke patients were recruited, only ninety-one patients completed del period (men = 53, 63.74%), with mean age 60.0±10.4 years (range, 34–82 years). The incidence of PSD was 27.47% two weeks after stroke. The occurrence of PSD was unrelated with age, stroke type, stroke lesion and the history of disease. In univariate analysis gender, PSD was correlated with female gender. In multivariate logistic regression analysis, poor stroke outcome (mRS≥3) (OR 12.113, CI 1.169 to 125.59, P<0.05) was the important predictors of PSD.

Conclusions

The study indicated that gender, functional dependence and stroke outcome are determinants of PSD occurrence during the first 2 weeks after stroke in China.     

FRET-FLIM Investigation of PSD95-NMDA Receptor Interaction in Dendritic Spines; Control by Calpain,CaMKII and Src Family Kinase

Little is known about the changes in protein interactions inside synapses during synaptic remodeling, as their live monitoring in spines has been limited. We used a FRET-FLIM approach in developing cultured rat hippocampal neurons expressing fluorescently tagged NMDA receptor (NMDAR) and PSD95, two essential proteins in synaptic plasticity, to examine the regulation of their interaction. NMDAR stimulation caused a transient decrease in FRET between the NMDAR and PSD95 in spines of young and mature neurons. The activity of both CaMKII and calpain were essential for this effect in both developmental stages. Meanwhile, inhibition of Src family kinase (SFK) had opposing impacts on this decrease in FRET in young versus mature neurons. Our data suggest concerted roles for CaMKII, SFK and calpain activity in regulating activity-dependent separation of PSD95 from GluN2A or GluN2B. Finally, we found that calpain inhibition reduced spine growth that was caused by NMDAR activity, supporting the hypothesis that PSD95-NMDAR separation is implicated in synaptic remodeling.     

Prevalence of Disease and Relationships between Laboratory Phenotype and Bleeding Severity in Platelet Primary Secretion Defects

Background

The prevalence of platelet primary secretion defects (PSD) among patients with bleeding diathesis is unknown. Moreover, there is paucity of data on the determinants of bleeding severity in PSD patients.

Objective

To determine the prevalence of PSD in patients with clinical bleeding and to study the relationships between the type of platelet defect and bleeding severity.

Methods

Data on patients referred for bleeding to the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan (Italy) in the years between 2008 and 2012 were retrieved to study the prevalence of PSD. Demographic, clinical and laboratory information on 32 patients with a diagnosis of PSD was used to compare patients with or without associated medical conditions and to investigate whether or not the type and extension of platelet defects were associated with the bleeding severity score (crude and age-normalized) or with the age at first bleeding requiring medical attention.

Results

The estimated prevalence of PSD among 207 patients with bleeding diathesis and bleeding severity score above 4 was 18.8% (95% confidence interval [CI]: 14.1–24.7%). Patients without associated medical conditions had earlier age of first bleeding (18 vs 45 years; difference: -27 years; 95% CI: -46 to -9 years) and different platelet functional defect patterns (Fisher''s exact test of the distribution of patterns, P = 0.007) than patients with accompanying medical conditions. The type and extension of platelet defect was not associated with the severity of bleeding.

Conclusions

PSD is found in approximately one fifth of patients with clinical bleeding. In patients with PSD, the type and extension of laboratory defect was not associated with bleeding severity.     

Postsynaptic density antigens: preparation and characterization of an antiserum against postsynaptic densities

Long-term immunization of rabbits with postsynaptic densities (PSD) from bovine brain produced an antiserum specific for PSD as judged by binding to subcellular fractions and immunohistochemical location at the light and electron microscope levels. (a) The major antigens of bovine PSD preparations were three polypeptides of molecular weight 95,000 (PSD-95), 82,000 (PSD-82), and 72,000 (PSD-72), respectively. Antigen PSD-95, also present in mouse and rat PSDs was virtually absent from cytoplasm, myelin, mitochondria, and microsomes from rodent or bovine brain. Antigens PSD-82 and PSD-72 were present in all subcellular fractions from bovine brain, especially in mitochondria, but were almost absent from rodent brain. The antiserum also contained low-affinity antibodies against tubulin. (b)Immunohistochemical studies were performed in mouse and rat brain, where antigen PSD-95 accounted for 90 percent of the antiserum binding after adsorption with purified brain tubulin. At the light microscope level, antibody binding was observed only in those regions of the brain where synapses are known to be present. No reaction was observed in myelinated tracts, in the neuronal cytoplasm, or in nonneuronal cells. Strong reactivity was observed in the molecular layer of the dentate gyrus, stratum oriens and stratum radiatum of the hippocampus, and the molecular layer of the cerebellum. Experimental lesions, such as ablation of the rat entorhinal cortex or intraventricular injection of kainic acid, which led to a major loss of PSD in well- defined areas of the hippocampal formation, caused a correlative decrease in immunoreactivity in these areas. Abnormal patterns of immunohistochemical staining correlated with abnormal synaptic patterns in the cerebella of reeler and staggerer mouse mutants. (c) At the electron microscopic level, immunoreactivity was detectable only in PSD. The antibody did not bind to myelin, mitochondria or plasma membranes. (d) The results indicate that antigen PSD-95 is located predominantly or exclusively in PSD and can be used as a marker during subcellular fractionation. Other potential uses include the study of synaptogenesis, and the detection of changes in synapse number after experimental perturbations of the nervous system.     

Are endogenous sex hormones related to DNA damage in paradoxically sleep-deprived female rats?

The aim of this investigation was to evaluate overall DNA damage induced by experimental paradoxical sleep deprivation (PSD) in estrous-cycling and ovariectomized female rats to examine possible hormonal involvement during DNA damage. Intact rats in different phases of the estrous cycle (proestrus, estrus, and diestrus) or ovariectomized female Wistar rats were subjected to PSD by the single platform technique for 96 h or were maintained for the equivalent period as controls in home-cages. After this period, peripheral blood and tissues (brain, liver, and heart) were collected to evaluate genetic damage using the single cell gel (comet) assay. The results showed that PSD caused extensive genotoxic effects in brain cells, as evident by increased DNA migration rates in rats exposed to PSD for 96 h when compared to negative control. This was observed for all phases of the estrous cycle indistinctly. In ovariectomized rats, PSD also led to DNA damage in brain cells. No significant statistically differences were detected in peripheral blood, the liver or heart for all groups analyzed. In conclusion, our data are consistent with the notion that genetic damage in the form of DNA breakage in brain cells induced by sleep deprivation overrides the effects related to endogenous female sex hormones.     

Association between Single-Nucleotide Polymorphisms of the Tyrosine Kinase Receptor B (TrkB) and Post-Stroke Depression in China

Background

Polymorphisms of the brain-derived neurotrophic factor (BDNF) have been investigated as candidate genes for post-stroke depression (PSD), and its receptor, neurotrophic tyrosine kinase receptor B (TrkB), has been associated with depression. However, no further data have yet reported the association between PSD and polymorphisms in TrkB. This study aims to investigate whether a relationship exists between TrkB polymorphisms and PSD.

Methods

A total of 312 depression patients (PSD patients) and 472 non-depression patient controls (NPSD patients) were recruited. All patients were evaluated using the Hamilton Rating Scale for Depression (HAMD) to determine depression severity, and PSD patients were diagnosed in accordance with DSM-V criteria. Three single-nucleotide polymorphisms (SNPs), namely, rs1187323, rs1212171, and rs1778929, in the TrkB gene were genotyped by high-resolution melt analysis.

Results

The SNP rs1778929 was significantly more associated with incident PSD in participants with the TT genotype than in those with CC (OR 0.482, 95% CI: 0.313–0.744). In terms of rs1187323, stroke was significantly more associated with incident depression in participants with the AC genotype than in those with AA (OR 0.500, 95% CI: 0.368–0.680). The minor allele (T) of rs1778929 (P = 0.024, OR = 0.725, 95% CI = 0.590–0.890) and the minor allele (C) of rs1187323 (P = 0.000, OR = 0.598, 95% CI = 0.466–0.767) were found to be significantly associated with PSD. Neither genotype nor allele frequencies of rs1212171 showed statistically significant differences between PSD and NPSD patients.

Conclusions

The results suggest that rs1778929 and rs1187323 in the TrkB gene are significantly associated with post-stroke depression in the Chinese population. Further studies are necessary to confirm our findings.     

出血性卒中后抑郁患者认知功能与生活质量的研究

目的:探讨不同时期出血性脑卒中后抑郁(Post-Stroke Depression,PSD)患者认知功能和生活质量的特征。方法:采用前瞻性队列研究,对57例PSD患者和91例非PSD(None PSD,NPSD)患者在基线期、6周和12周后分别进行临床神经功能缺损程度评分量表(China Stroke Scale,CSS)、汉密尔顿抑郁量表(Hamilton Depression Scale,HAMD)、蒙特利尔认知评估量表(Montreal Cognitive Assessment,Mo CA)和Barthel指数(Barthel Index,BI)的评估。结果:基线期PSD和NPSD患者Mo CA总分[分别为(11.6±2.9)分、(11.2±3.1)分]和BI总分[分别为(45.6±8.3)分、(46.2±7.2)分],差异无统计学意义(P0.05);治疗6周和12周后PSD组Mo CA总分[分别为(13.4±2.3)分、(18.2±3.2)分]和BI总分[分别为(63.8±6.5)分、(77.2±4.1)分]均低于NPSD组[分别为(15.8±2.8)分、(22.6±2.4)分;(72.2±7.5)分、(85.8±5.6)分],差异有统计学意义(P0.000)。结论:在卒中的康复后期,PSD患者较NPSD患者认知功能障碍损害更严重,生活质量更差。推测认知功能是PSD患者长期预后的独立预测因素,可为PSD患者康复策略的制定提供帮助。     

Molecular mechanisms underlying specificity of excitotoxic signaling in neurons

The central role of glutamate receptors in mediating excitotoxic neuronal death in stroke, epilepsy and trauma has been well established. Glutamate is the major excitatory amino acid transmitter within the CNS and it's signaling is mediated by a number of postsynaptic ionotropic and metabotropic receptors. Although calcium ions are considered key regulators of excitotoxicity, new evidence suggests that specific second messenger pathways rather than total Ca(2+) load, are responsible for mediating neuronal degeneration. Glutamate receptors are found localized at the synapse within electron dense structures known as the postsynaptic density (PSD). Localization at the PSD is mediated by binding of glutamate receptors to submembrane proteins such as actin and PDZ containing proteins. PDZ domains are conserved motifs that mediate protein-protein interactions and self-association. In addition to glutamate receptors PDZ-containing proteins bind a multitude of intracellular signal molecules including nitric oxide synthase. In this way PDZ proteins provide a mechanism for clustering glutamate receptors at the synapse together with their corresponding signal transduction proteins. PSD organization may thus facilitate the individual neurotoxic signal mechanisms downstream of receptors during glutamate overactivity. Evidence exists showing that inhibiting signals downstream of glutamate receptors, such as nitric oxide and PARP-1 can reduce excitotoxic insult. Furthermore we have shown that uncoupling the interaction between specific glutamate receptors from their PDZ proteins protects neurons against glutamate-mediated excitotoxicity. These findings have significant implications for the treatment of neurodegenerative diseases using therapeutics that specifically target intracellular protein-protein interactions.     

Bone marrow and peripheral white blood cells number is affected by sleep deprivation in a murine experimental model

Sleep deficit and related disorders are becoming increasingly prevalent in modern life and an extensive literature has documented that acute or chronic sleep deprivation can lead to several physiological consequences. Here, we evaluated the effects of sleep deprivation on hematopoietic composition of either bone marrow or peripheral blood. Mice were subjected to paradoxical sleep deprivation (PSD) for 72 h by modified multiple platform method, with or without an additional sleep recovery (SR) period of 10 days. PSD decreased total cellularity of the bone marrow and peripheral blood concomitantly. Subsequent analysis of cell composition showed that absolute number of hematopoietic stem/progenitor cells and colony-forming units was decreased. Moreover, the absolute number of granulocytes and monocytes in bone marrow was reduced in PSD group. These alterations were paralleled by an accumulation of neutrophils and monocytes in peripheral blood. PSD also induced lymphopenia in the circulation. To the best of our knowledge, this is the first study that demonstrates the importance of sleep on the hematopoietic microenvironment and provides new insights into the relationship between sleep and the immune system.