精神分裂症幻听症状神经机制的研究进展

<正>幻听是精神分裂症最常见的症状之一,其出现频率高于任何其他类型幻觉,可作为临床诊断、判断精神分裂症严重程度以及治疗效果的重要依据之一。揭示幻听的神经机制,不仅具有显著临床意义,还有助于探讨精神分裂症的病理生理机制。本文将从神经影像学、电生理、遗传学等方面对其做一系列综述。1神经影像学研究精神分裂症患者影像学检查通常并不表现出脑结构异常,但随着科学技术发展,不断涌现的脑成像新技术及数据     

磁共振质子波谱分析首发精神分裂症患者脑内谷氨酸能水平的研究进展

随着神经影像学在精神分裂症中的研究不断发展,对精神分裂症的病因假说相关的神经 生化递质也不断深入,谷氨酸作为精神分裂症病因学假说的重要补充,在精神分裂症病理生理机制中 有着至关重要的地位。现对磁共振质子波谱的基本原理及其分析首发精神分裂症患者脑中谷氨酸能水 平的研究进展作一综述。     

精神分裂症发病的一种新学说:神经末梢异常再分布

神经病理学和脑影像学研究发现许多精神分裂症患者具有脑损害。这些脑损害能够引起神经细胞轴突侧支的增生、突触增殖和神经通路重组。这类变化可能系生理性的适应,但也可能由此导致另一种意义的损害。据此认为异常的神经末梢再分布在精神分裂症的病理生理过程中具有特殊作用。     

精神分裂症脑神经影像学及神经病理学的研究进展

精神分裂症的病因及发病机制迄今未明。影像学、神经化学、分子生物学等方法的快速发展和应用 ,使人们能够从宏观及微观两个水平 ,对精神分裂症大脑的神经病理学改变有更多认识 ,从而不断加深对精神分裂症病因及发病机制的理解。我们结合精神分裂症脑影像学和尸检大脑神经病理学研究的文献复习 ,对其研究进展作简要论述。一、大体结构改变1 脑室和脑皮质 :精神分裂症患者的脑室扩大和脑体积减小 ,是有关的影像学研究结果一致性很高的发现[1,2 ] 。如在超过 10 0篇CT的研究中 ,75 %报道精神分裂症患者有侧脑室扩大 ,83%报道第 3脑室扩大 ,6 …     

精神分裂症影像基因组学研究进展

影像学技术已成为研究大脑结构和功能的重要工具,此技术已经初步运用于对精神分裂症患者脑结构和功能的研究,发现精神分裂症患者的脑结构和功能均存在异常。而遗传基因在精神分裂症患者大脑发育过程中起着重要作用。影像学和基因组学结合起来的研究技术可以探索和评价大脑相关基因对脑功能的影响,从而了解这些基因对精神分裂症行为的影响。现就有关精神分裂症影像基因组学方面研究进行综述。     

精神分裂症神经电生理的研究进展

精神分裂症是一种病因不明、预后欠佳的复杂重性精神疾病,目前诊断精神分裂症主要依据临床症状,电生理及影像学特征不能作为诊断依据,但大量研究结果提示,精神分裂症患者脑结构和功能异常是发病的病理生理基础。随着脑成像技术的发展,特别是当前功能神经影像学已成为精神分裂症研究的热点之一,多种设备联合检测技术的运用,使精神疾病的研究将进入了多学科和多模态的发展阶段［1］。功能神经影像学主要包括脑电图（EEG ）／脑电地形图（BEAM ）及诱发电位、多导睡眠图（PSG）、脑电超慢涨落图（EFG ）、脑磁图（M EG ）及磁源性成像（MSI）、功能磁共振成像（fMRI）、正电子发射计算机断层显像（PE T ）和单光子发射计算机断层成像（SPECT ）,均从不同角度研究大脑的功能［2］。fMRI、PET及SPECT 检测均依赖局部脑血流,是神经元活动的间接反应,受时间分辨率不高等因素的限制。EEG／BEAM 、诱发电位、PSG、EFG、M EG 及MSI均属于神经电生理检测方法。EEG／BEAM 具有可长时间连续监测和成本低廉等优势,在精神分裂症的研究中具有重要价值;PSG 能够准确检测精神分裂症患者睡眠障碍的严重程度;EFG 是一种用于精神科的新技术,具有广阔前景;M EG的时间、空间分辨率高,干扰少,具有无法比拟的优势［2－3］。目前,精神分裂症神经电生理的相关研究较少,现对此复习文献并综述如下。     

MBP和GFAP及其基因多态性在精神分裂症中的研究进展

精神分裂症是一种病因尚未完全阐明的常见的重性精神病,其疾病过程、致病因素及如何造成其长期病理生理的改变尚不清楚.既往认为精神分裂症是一种功能性疾病,没有脑器质性改变.但随着神经病理学、神经影像学等的发展,越来越多的证据支持精神分裂症存在着脑器质性改变,包括大脑皮层、白质、颞叶及基底等病变,如何用特异性生化指标确定精神分裂症发作致脑损害的存在与否或评价其损害程度是学者们长期讨论的课题,近来的研究表明血液中髓鞘碱性蛋白和神经胶质纤维酸性蛋白水平的变化可反映脑内中枢神经的损伤程度,然而这些生化指标能否作为精神分裂症病程呈进行性进展且具有程度不等的认知功能障碍的指标有待探讨.本文就精神分裂症患者血液髓鞘碱性蛋白(MBP)和胶质纤维酸性蛋白(GFAP)的浓度变化及其基因多态性和认知功能与精神分裂症患者的神经系统损伤的关系作一些阐述.     

精神分裂症的认知障碍与脑影像研究

本文复习了结构性脑影像和功能性脑影像学与精神分裂症的认知功能障碍研究的最新进展     

精神分裂症的认知障碍与脑影像研究

本文复习了结构性脑影像和功能性脑影像学与精神分裂症的认知功能障碍研究的最新进展。     

中国精神分裂症的神经影像学研究进展(英文)

自Hounsfield于1972年首次报道X线计算机断层扫描(CT)后,神经影像学技术应用持续发展,用于研究大脑结构、功能和生物化学等方面。本文就中国近年来对精神分裂症结构性和功能性神经影像学的研究做了一个概述并且用4个表格来描述中国大陆所有相关研究。国内在精神科领域使用神经影像学技术的首个研究报告可追溯至1983年,研究发现30%精神分裂症患者存在脑萎缩。上世纪90年代国内逐渐出现功能神经影像学研究,并且快速发展。近年来,脑结构网络和脑功能网络研究已成为中国神经影像学研究的一个热门话题。     

Tissue with high intelligence quotient Adipose-derived stem cells in neural regeneration

The aim of the present review is to highlight the possible neuroregenerative potential ol adipose-derived stem cells. The key property of stem cells is plasticity including self-renewal, multilineage differentiation, and migration, whereas the required property is transplantability. For a long time, embryonic stem cells were thought to be the only source of pluripotency, a dogma that has been challenged during the last decade. Today, an alternative option might be adipose-derived stem cells, as easily accessible, ethical and autologous cellular source. Recent knowledge of adipobiology increasingly recognizes that adipose tissue is the major endo- and paracrine organ of the human body. Likewise, numerous neuropetides, neurotrophic factors, neurotransmitters, hypothalamic and steroid hormones and their receptors are shared by adipose tissue and brain. Accordingly, the regenerative potential of neuroprotective factor-secreting adipose-derived stem cells is outlined. Whether the possible benefits of adipose stem cell-based therapy may be mediated via cell transdifferentiation and/or paracrine mechanisms remains to further be evaluated.     

人参皂甙Rg1对去卵巢大鼠面神经核脑源性神经营养因子表达的影响：半定量分析

BACKGROUND： Estrogen is neuroprotective effects such as breast carcinoma, endometria but long-term estrogen treatment can induce side cancer, and stroke. However, phytoestrogen is neuroprotective without these side effects. OBJECTIVE： To study the effects of Ginsenoside Rgl on facial neurons and brain-derived neurotrophic factor （BDNF） expression in the facial nucleus in ovariectomized rats. DESIGN, TIME AND SETTING： The randomized, controlled animal experiments were performed at the Ultrasonic Institute, Second Affiliated Hospital, Chongqing Medical University, China, from September 2007 to September 2008. MATERIALS： Ginsenoside Rgl （Sigma, USA）, rabbit anti-rat BDNF, Bcl-2, Bax antibodies, biotin-labeled goat anti-rabbit IgG （Boster, China）, and a TUNEL kit （Roche, Germany） were used in this study. METHODS： A total of 48 adult Sprague Dawley rats undergoing ovariectomy were randomly assigned into sham operation （n = 8）, model （n = 20）, and Ginsenoside Rgl （n = 20） groups. Facial nerve damage was induced by bilateral clamping of the facial nerve trunk. The bilateral facial nerve trunk was exposed in the sham operation group, with no clamping. Rats in the Ginsenoside Rgl group were intraperitoneally injected with 10 mg/kg per day Ginsenoside Rgl; other groups received 2 mL saline, once a day, for 14 days. MAIN OUTCOME MEASURES： Morphologic changes in neurons of the facial nucleus were observed following hematoxylin-eosin staining. Neuronal apoptosis was detected by TUNEL. Changes in ultrastructure of the facial nerve fibers were observed with a transmission electron microscope. Expression of BDNF, Bcl-2, and Bax protein was quantified by semiquantitative immunohistochemistry. RESULTS： At 3-14 days following facial nerve damage, Ginsenoside Rgl increased BDNF expression and the number of regenerated nerve fibers, and produced thicker myelin sheaths （P 〈 0.05）. Ginsenoside Rgl also gradually increased Bcl-2 protein expression and decreased Bax protein expression （P 〈 0.05）. By day 7, apoptosis was observed in facial neurons, but Ginsenoside Rgl reduced the number of apoptotic neurons. Sham animals did not show any changes in BDNF, Bcl-2, or Bax expression or facial neuron morphology. CONCLUSION： Ginsenoside Rgl can substantially inhibit facial neuronal apoptosis by increasing endogenous BDNF and Bcl-2 expression and by decreasing Bax expression in ovariectomized rats after facial nerve damage.     

Hippocampal CA1 pyramidal cells and neurotrophic factors in a rat model of vascular dementia following Xiongma drop pill versus Ginkgo leaf tablets

BACKGROUND： Previous studies have demonstrated the neuroprotective effects of Xiongma drop pill （XMDP） in a mouse model of vascular dementia. Neurotrophic factors play an important role in repair and regeneration of injured neurons. OBJECTIVE： To compare the effects of XMDP and Ginkgo leaf tablets on the appearance and number of hippocampal CA1 pyramidal neurons, as well as neurotrophic factor content in brain tissues, during vascular dementia formation to explore the neuroprotective mechanisms of XMDP. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Pharmacology, College of Pharmacy, Harbin University of Commerce between April 2007 and December 2008. MATERIALS： XMDP was prepared by the College of Pharmacy, Harbin University of Commerce, with each 40 mg pill containing ferulic acid （≥ 0.149 mg） and gastrodin （≥ 0.171 mg）. Ginkgo leaf tablets were purchased from Taiyuan Qianyuan Pharmacy, China. METHODS： Healthy, adult, male, Wistar rats were randomly assigned to 6 groups： sham-operation, model, XMDP （high-, middle-, and low- dose）, and Ginkgo leaf tablets. The 6 groups were subdivided into two subgroups according to administration days, i.e., 30 and 60 days, with 8 animals in each subgroup. Rats in the model, XMDP, and Ginkgo leaf tablets groups were subjected to permanent bilateral ligation of the common carotid artery to establish a vascular dementia model. At 8 days after model establishment, all groups received intragastric administration once daily of the following： 10 mL/kg normal saline in the sham-operation and model groups; 0.4, 0.2, and 0.1 g/kg XMDP in the high-, middle-, and low-dose XMDP groups, respectively; and 50 mg/kg Ginkgo leaf tablets in the Ginkgo leaf tablets group. MAIN OUTCOME MEASURES： Hematoxylin-eosin staining was used to observe appearance and to quantify the number of hippocampal CA1 pyramidal neurons. Brain-derived neurotrophic factor and nerve growth factor concentrations in brain tissues were detected by enzyme-linked immunosorbent assay. RESULTS： Following model establishment, hippocampal CA1 neurons exhibited pathological changes. Compared with the sham-operation group, the number of pyramidal neurons significantly decreased （P 〈 0.05 or P 〈 0.01）, and neurotrophic factor concentration increased in the model rats （P 〈 0.05 or P 〈 0.01）. XMDP attenuated neuronal injury in a dose-dependent manner： the number of pyramidal neurons and neurotrophic factor concentrations were significantly increased compared with the model group （P〈 0.05 or P〈 0.01）. High- and middle-dose XMDP resulted in equivalent effects to Ginkgo leaf tablets. In addition, neurotrophic factor concentrations in all XMDP groups, after 60 days of administration, were remarkably greater than corresponding concentrations at 30 days （P 〈 0.05 or P 〈 0.01 ）. CONCLUSION： Hippocampal CA1 pyramidal cells exhibited pathological injury following establishment of the vascular dementia model. Middle- and high-dose XMDP increased neurotrophic factor expression in the brain of vascular dementia rats, which suggested neuroprotection equivalent to Ginkgo leaf tablets.     

Association of single nucleotide polymorphisms of brain-derived neurotrophic factor gene and multidrug resistance 1 gene to refractory epilepsy in Chinese Han children

BACKGROUND： There are two hypotheses for the underlying cause of refractory epilepsy： ＂target＂ and ＂transport＂. Studies have shown that brain-derived neurotrophic factor （BDNF） is over-expressed in refractory epilepsy. Multidrug resistance 1 （MDR1） gene encodes for P-glycoprotein, the primary ATP-binding cassette transporter in the human body. Some single nucleotide polymorphisms of the MDR1 gene have been associated with refractory epilepsy. OBJECTIVE： To investigate the association between BDNF gene C270T polymorphism and MDR1 T-129C polymorphism with refractory epilepsy in Chinese Han children through the use of polymerase chain reaction （PCR）-restriction fragment length polymorphism analysis. DESIGN, TIME AND SETTING： A case-control, genetic association study was performed at the Central Laboratory, Third Xiangya Hospital of Central South University from June 2005 to November 2007. PARTICIPANTS： A total of 84 cases of unrelated children with epilepsy, including 41 cases of refractory epilepsy and 43 cases of drug-responsive epilepsy, were enrolled. An additional 30 healthy, Chinese Han children, whose ages and gender matched the refractory epilepsy patients, were selected as normal controls. METHODS： Venous blood was collected and genomic DNA was extracted from the blood specimens. C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene were genotyped using PCR-restriction fragment length polymorphism analysis. Association analysis using the Ftest and Chi-square test was statistically performed between C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene and refractory epilepsy. MAIN OUTCOME MEASURES： The distribution of genotypes and allele frequencies of C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene. RESULTS： The distribution of CC, CT, and TT genotypes, as well as C and T allele frequencies, in the BDNF gene was not significantly different between the refractory epilepsy group, drug-responsive epilepsy group, or the normal control group （P 〉 0.05）. The distribution of TT genotype and T allele frequencies of the MDR1 gene was significantly different in the refractory epilepsy group compared with the drug-responsive epilepsy and normal control groups （P 〈 0.05）. Comparison of haplotype combinations demonstrated that there were no significant differences in combinations of TT＋CC, -FI-＋CT, TC＋CC, and TC＋CT among the three groups （P 〉 0.05）. CONCLUSION： C270T polymorphism of the BDNF gene was not associated with refractory epilepsy in Chinese Han children, but T-129C polymorphism in the MDR1 gene was associated with refractory epilepsy in Chinese Han children. The TT genotype and T allele frequencies could serve as susceptibility loci for refractory epilepsy. Interactions between C270T in BDNF gene and T-129C in MDR1 gene were not observed in refractory epilepsy in Chinese Han children.     

转化生长因子β和脑源性神经营养因子联合诱导成年大鼠骨髓基质细胞向神经元样细胞的分化

BACKGROUND： It has been demonstrated that transforming growth factor-β （TGF-β） and brain- derived neurotrophic factor （BDNF） can induce stem cell differentiation into neuron-like cells. OBJECTIVE： To investigate the efficacy of TGF-β and BDNF at inducing the differentiation of adult rat bone marrow stromal cells （BMSCs） into neuron-like cells, both in combination or alone. DESIGN, TIME AND SETTING： A comparative observation experiment was performed at the Department of Orthopedics, First Affiliated Hospital of Liaoning Medical University between October 2007 and January 2008. MATERIALS： TGF-~ and BDNF were purchased from Sigma, USA; mouse anti-rat neuron specific enolase, neurofilament and glial fibrillary acidic protein were purchased from Beijing HMHL Biochem Ltd., China. METHODS： BMSCs were isolated from rats aged 4 weeks and incubated with TGF-β（1μ g/L） and/or BDNF （50 μ g/mL）. MAIN OUTCOME MEASURES： Expression of neuron-specific enolase, neurofilament and glial fibrillary acidic protein were determined by immunocytochemistry. RESULTS： BMSCs differentiated into neuron-like cells following induction of TGF-β and BDNF, and expressed both neuron-specific enolase and neurofilament. The percent of positive cells was significantly greater in the combination group than those induced with TGF-β or BDNF alone （P 〈 0.01）. CONCLUSION： Treatment of BMSCs with a combination of TGF-β and BDNF induced differentiation into neuron-like cells, with the induction being significantly greater than with TGF-β or BDNF alone.     

Environmental factors in the development and progression of late-onset Alzheimer＇s disease

Late-onset Alzheimer＇s disease （LOAD） is an age-related neurodegenerative disorder characterized by gradual loss of synapses and neurons, but its pathogenesis remains to be clarified. Neurons live in an environment constituted by neurons themselves and glial cells. In this review, we propose that the neuronal degeneration in the AD brain is partially caused by diverse environmental factors. We first discuss various environmental stresses and the corresponding responses at different levels. Then we propose some mechanisms underlying the specific pathological changes, in particular, hypothalamic-pituitary adrenal axis dysfunction at the systemic level; cerebrovascular dysfunction, metal toxicity, glial activation, and Aβ toxicity at the intercellular level; and kinase-phosphatase imbalance and epigenetic modification at the intracellular level. Finally, we discuss the possibility of developing new strategies for the prevention and treatment of LOAD from the perspective of environmental stress. We conclude that environmental factors play a significant role in the development of LOAD through multiple pathological mechanisms.     

Effects of brain-derived neurotrophic factor on induced differentiation of SH-SY5Y cells in vitro

BACKGROUND： Previous studies have demonstrated that brain-derived neurotrophic factor （BDNF） promotes neural differentiation. However, the mechanisms involved in cell cycle-related protein regulation, which highly correlates to neural proliferation and apoptosis, remain poorly understood. OBJECTIVE： To investigate the effects of various concentrations of BDNF on cycle-related protein mRNA expression in induce-differentiated SH-SY5Y cells in vitro prior to and following G2 phase, and to analyze the neuroprotective effects of BDNF. DESIGN, TIME AND SETTING： A comparison, observational study, based on cell biology, was performed at the Department of Biochemistry, Medical College of Tongji University, from March 2005 to October 2006. MATERIALS： SH-SY5Y cells were provided by Shanghai Institute of Cytology, Chinese Academy of Science; BDNF by Alomone Labs, Israel; all-trans retinoic acid （ATRA） by Sigma-Aldrich, USA. METHODS： SH-SY5Y cells were randomly divided into three groups： blank control [cells were treated in Insulin-Transferrin-Selenium （ITS） solution for 7 days], ATRA （cells were treated with ITS solution containing 10 μmol/L ATRA for 7 days）, and BDNF （cells were treated identical to the ATRA group for 5 days, and then respectively treated in ITS solution containing 1, 10, and 100 μg/L BDNF for 2 days）. The experiment was repeated three times for each group. MAIN OUTCOME MEASURES： mRNA expression levels of cyclin A1, B1, B2, cyclin-dependent kinase 1, and 5 were detected using quantitative real-time RT-PCR; percentage of cells in G1, S, and G2 phases were detected using fluorescence-activated cell sorting. RESULTS： mRNA expression levels of cyclin A1 in the high-dose BDNF group was significantly less than the ATRA group （P 〈 0.05）.mRNA expression levels of cyclin B1 was significantly less in the different BDNF concentration groups compared with the control and ATRA groups （P 〈 0.05 or P 〈 0.01）. mRNA expression levels of cyclin B2 and cyclin-dependent kinase 1 were significantly decreased in the high-dose BDNF group （P 〈 0.05 or P 〈 0.01）. Cyclin-dependent kinase 5 mRNA expression was significantly greater in the low-dose and moderate-dose BDNF groups compared with the ATRA group （P 〈 0.05）. The percentage of cells in G1 phase was significantly greater in the different BDNF concentration groups compared with the ATRA and control groups （P 〈 0.01）. Moreover, the percentage of cells in S phase was significantly less in the three BDNF groups compared with the ATRA group （P 〈 0.01）. However, the percentage of cells in S phase was significantly less in the low-dose and high-dose BDNF groups compared with the control group （P 〈 0.01）. CONCLUSION： BDNF enhanced the percentage of cells in G1 phase, but did not alter mRNA expression of cell cycle-related proteins prior to or following G2 phase. These results suggested that BDNF was not a risk factor for inducing apoptosis.     

高血压脑出血的显微外科治疗进展

高血压脑出血（Hypertensive intrac-rebral hemorrhage,HICH）是具有高发病率、高病死率、高致残率的急性脑血管疾病,占所有脑卒中患者的10%-20%,早期病死率可高达49.4%。随着人口老龄化,其发病率逐年提高;而外科手术的干预,使其病死率有所下降,但致残率居高不下。如何提高手术疗效和患者生存质量,一直是神经外科医师努力的方向。微侵袭血肿清除术因其手术创伤小,恢复快,是目前国内治疗高血压脑出血的重要手段。     

神经内镜联合亚低温治疗高血压基底节区脑出血

目的 探讨神经内镜联合亚低温在治疗高血压基底节区脑出血中的临床应用价值.方法 回顾性分析我院神经内镜治疗高血压基底节区脑出血患者40例的临床资料,并对治疗结果进行分析.结果 神经内镜治疗组22例(甲组),神经内镜联合亚低温治疗组18例(乙组),术后3个月根据GCS评分,甲组恢复良好1例,中残4例,重残6例,植物生存6例,死亡5例;乙组恢复良好4例,中残8例,重残3例,植物生存1例,死亡2例,两组比较差异有统计学意义(P＜0.05).两组颅内压比较第1天两者差异不明显,但第2、3天亚低温组颅内压明显降低.结论 神经内镜是治疗高血压基底节区脑出血较为有效的手术方式,联合亚低温治疗能有效降低颅内压,改善术后神经功能恢复,具有较好的临床应用价值.