经侧脑室注射脂多糖诱导大鼠黑质部位小胶质细胞激活及多巴胺能神经元损伤的研究

目的观察经脑室注射脂多糖(LPS)后大鼠的黑质部小胶质细胞激活及多巴胺(DA)能神经元的变化,探讨脑内炎性反应在黑质DA能神经元慢性变性过程中的作用。方法健康雄性SD大鼠30只,随机分为生理盐水(NS)对照组和LPS组,分别向大鼠右侧脑室注射20μL NS或50μg LPS,40周后用免疫组织化学方法检测大鼠黑质小胶质细胞是否激活、激活的程度(OX-42及OX-6抗体水平),以及酪氨酸羟化酶(TH)阳性神经元的形态和数量。以Fluoro-Jade B(FJB)染色法检测黑质部位神经元变性情况。结果 (1)NS对照组大鼠黑质部位OX-42阳性小胶质细胞呈静息状态,染色浅。LPS组大鼠黑质部OX-42阳性小胶质细胞呈部分激活状态,染色深。两组大鼠黑质部位均未发现OX-6阳性小胶质细胞。(2)NS对照组大鼠黑质部位有大量深染的TH阳性神经元。LPS组大鼠黑质部位TH阳性染色神经元数目(99.11±20.31)比NS对照组(189.52±12.12)减少47.7%(P<0.01)。(3)两组大鼠黑质部位均未见FJB阳性染色神经元。结论经侧脑室单次注射LPS可能造成大鼠黑质部位小胶质细胞长期慢性激活及DA能神经元慢性迟发性功能性损伤。     

黑质内注射脂多糖对不同年龄大鼠DA能神经元和小胶质细胞活性的影响

目的 探讨青年和老年大鼠黑质DA能(DA)神经元对脂多糖(LPS)所诱导的损伤作用的敏感性差异和对小胶质细胞活性的影响.方法 采用立体定向技术向大鼠单侧黑质内注入LPS建立PD大鼠模型;采用免疫组化法观察黑质酪氨酸羟化酶(TH)阳性细胞和OX6阳性小胶质细胞变化;采用Fluoro-Jade B染色法检测黑质的变性神经元.结果 黑质内注射LPS后,老年组大鼠黑质区TH阳性神经元数量较青年组明显减少(P<0.01);老年组大鼠黑质区Fluoro-Jade B阳性神经元明显多于青年组(P<0.01);青年组大鼠黑质部位的OX6阳性小胶质细胞主要是处在激活期的;而老年组大鼠黑质部位的OX6阳性小胶质细胞主要是活化期的(阿米巴样或巨噬细胞样).结论 老年大鼠的黑质DA能神经元对于LPS所诱导的损伤作用较青年大鼠更为敏感.     

p38MAPK信号通路在小胶质细胞激活介导多巴胺能神经元变性中的作用研究

目的:研究p38丝裂原激活蛋白激酶(p38MAPK)在脂多糖(LPS)诱导小胶质细胞激活介导多巴胺(DA)能神经元变性中的作用。方法:脑立体定位注射LPS于大鼠脑黑质,Western blot印记法检测不同时间点(0、0.5h、1h、6h、12h)黑质p38磷酸化水平。酪氨酸羟化酶(Tyrosine hydroxylase,TH)免疫组织化学染色观察蛋白激酶(MAPK)特异性抑制剂SB203580预处理后LPS对DA能神经元变性的影响。结果:黑质注射LPS后,Western blot结果显示p38MAPK总体蛋白水平在各组均存在表达,无显著性差异(P>0.05),而其磷酸化p-p38MAPK却发生了明显变化。正常对照组和PBS注射侧几乎无p-p38的表达,LPS注射后30min,p-p38即有少量的表达;1h表达量增加;6h表达量达高峰;12h后表达量逐渐下降。与PBS对照侧相比,LPS注入黑质导致TH阳性细胞数下降至38%;SB203580预处理可以显著增加TH+细胞数达63%(P<0.05)。结论:p38MAPK信号通路参与了LPS诱导小胶质细胞激活介导DA能神经元变性,可通过阻断信号通路来减轻LPS诱导DA能神经元变性,为PD治疗提供新的思路。     

青藤碱防护脂多糖所致PD大鼠黑质多巴胺能神经元损伤实验研究

目的观察中药青藤碱(SN)对脂多糖(LPS)所致大鼠黑质多巴胺能(DA)神经元损伤的保护作用。方法黑质内注射LPS制作PD大鼠模型。应用SN对实验动物进行预处理。实验分为对照组、PD组及SN组,采用行为学、酪氨酸羟化酶(TH)、环氧化酶-2(COX-2)等免疫组化及免疫印迹技术等观察SN对LPS所致黑质DA能神经元损伤的保护作用。结果对照组大鼠无任何行为变化,PD组大鼠平均旋转圈数为196.90±9.52,SN组明显减少,为98.79±8.81,差异非常显著(P<0.01)。TH免疫组化表明对照组黑质TH阳性神经元数量较多,胞体较大,突起明显;PD组TH阳性神经元数量明显减少,甚至消失,神经元胞体萎缩,突起亦不清晰,差异非常显著(P<0.01)。SN组TH阳性神经元数量与PD组相比明显增加(P<0.01),神经元形态变化亦不明显。COX-2免疫组化表明对照组黑质致密部偶见COX-2阳性细胞,PD组可见大量散在分布的COX-2阳性细胞,SN组COX-2阳性细胞数与PD组相比明显减少,差异非常显著(P<0.01)。小胶质细胞特异性抗体(OX-42)免疫组化表明对照组大鼠黑质小胶质细胞多呈静止的分枝样状态,PD组多...     

凝血酶诱导小胶质细胞激活与黑质多巴胺能神经元变性关系的研究

目的探讨凝血酶诱导小胶质细胞激活与黑质多巴胺（DA）能神经元变性的关系。方法采用脑立体定向术将凝血酶注射人大鼠黑质，采用尼氏（Nissl）染色、酪氨酸羟化酶（TH）及特异性小胶质细胞表面补体受体（CR3）单克隆抗体（OX-42）标记免疫组织化学染色，观察凝血酶注射人大鼠黑质后不同时间点TH阳性多巴胺能神经元数量及小胶质细胞的激活情况。结果凝血酶注入黑质4h后小胶质细胞开始呈现“灌木丛样”或少量呈现阿米巴样；12h小胶质细胞数目明显增加且绝大部分呈现阿米巴样；24h已完全激活，“阿米巴样”细胞达高峰；3d维持高峰；14d后小胶质细胞染色变淡，体积变小，阿米巴样细胞数目下降。TH阳性细胞数在第3d开始下降，第7d有大量的TH阳性细胞丢失，与对照侧相比下降达约53％（P〈0．01），高倍镜下可见胞体皱缩、突起明显缩短或减少，14d时细胞数下降至21％，30d时约为12％（P〈0．01）。结论凝血酶对DA能神经元具有一定的损毁作用，小胶质细胞的激活先于DA能神经元变性，其活化可能参与DA能神经元变性。     

脂多糖对多巴胺能神经元的损毁作用及其机制研究

目的观察脂多糖(1ipopolysaccharide．LPs)对黑质多巴胺(dopamine，DA)能神经元的损毁作用，探讨免疫机制与帕金森病(Parkinsondisease，PD)发病的相关性。方法采用立体定向术将LPS注人大鼠单侧黑质后分别于注射后2、3、4周经腹腔注射阿朴吗啡诱发动物旋转行为；采用高效液相色谱一电化学法(high performanee liquid chromatography，HPLC)测定纹状体和黑质部位DA等单胺类递质含量；采用免疫组化法检测黑质酪氨酸羟化酶(tyrosine hydroxylase，TH)阳性细胞数；采用尼(氏)染色(Nissl)观察小胶质细胞的活化和以双重免疫酶染色法观察小胶质细胞活化和诱导型一氧化氮合酶(inducible nitric oxide，iNOS)合成。结果大鼠单侧黑质注人LPS后2、3、4周，以阿朴吗啡诱发大鼠均出现旋转行为，其损伤侧纹状体和黑质DA及其代谢物含量降低了30%～70%，注射侧的黑质TH阳性细胞数减少，尤以3周和4周为甚．尼(氏)染色和双重免疫酶染色法也分别显示LPS注射侧小胶质细胞活化，同时伴有iNOS合成的增加。结论LPS对DA能神经元具有一定的损毁作用，小胶质细胞的活化及其释放的NO有可能参与该细胞死亡，提示免疫机制与PD的发病可能存在相关性。     

S-甲基异硫脲对脂多糖诱导多巴胺能神经元变性的保护作用

目的　 探讨诱导型一氧化氮合酶 (iNOS)抑制剂S 甲基异硫脲 (S methylisourea ,SMT)对脂多糖(lipopolysaccharide ,LPS)诱导多巴胺 (DA)能神经元变性的保护作用及其机制。 方法　 4 8只大鼠随机分成 4组(n =12 ) :磷酸缓冲液 (PBS)对照组、LPS组、生理盐水治疗对照组和SMT治疗组 ;此 4组又各分成 1,7d两个亚组。立体定向注射 5 μgLPS致大鼠脑黑质建立PD炎症模型 ,采用化学比色法检测 1d亚组黑质内NO释放量以及iNOS活性改变 ;RT PCR检测iNOSmRNA的表达 ;酪氨酸羟化酶 (tyrosinehydroxylase ,TH)免疫组织化学染色观察 7d亚组黑质DA能神经元的损伤情况。结果　 与PBS对照组相比 ,LPS注入黑质导致TH阳性细胞数下降至 35 % (P <0 .0 5 ) ;同时黑质内NO含量 ,iNOS活性及iNOSmRNA表达明显增高 ;SMT治疗组NO释放量 ,iN OS活性及iNOSmRNA表达显著降低 (P <0 .0 1) ;TH阳性细胞数亦明显增多 ,达 70 % (P <0 .0 5 ) ,生理盐水治疗组对此无明显改善。结论　iNOS上调是LPS诱导DA能神经元变性机制中重要的因素之一 ,iNOS特异性抑制剂SMT可以显著抑制LPS诱导DA能神经元变性及iNOSmRNA的高表达     

蛋白酶体抑制剂诱导多巴胺能神经元变性伴包涵体形成

目的 观察蛋白酶体抑制剂诱导黑质多巴胺(DA)能神经元变性伴胞浆内包涵体形成，探讨蛋白酶体功能在帕金森病发病机制中的作用。方法将蛋白酶体抑制剂Lactacystin立体定向注射至大鼠黑质部位。免疫荧光观察黑质区DA神经元变性缺失及胶质细胞变化。免疫荧光双标法观察DA能神经元内蛋白聚集的包涵体及其主要成分α-共核蛋白(α-synuclein)、Parkin和泛素(ubiquitin)的表达。同时观察。DA能神经元发生细胞凋亡。结果注射Lactacystin第7天大鼠开始出现自发性活动减少，阿扑吗啡可诱导出旋转行为；3周后黑质部位酪氨酸羟化酶(TH)阳性细胞减少，呈剂量依赖性；小胶质细胞增生明显。TH与硫磺素、硫磺素与α-synuclein、硫磺素与Parkin、以及硫磺素与ubiquitin复合染色呈阳性；TH与TUNEL双染亦呈阳性。结论Lactacystin对多巴胺能神经元具有毒性作用，且导致蛋白聚集，包涵体形成。蛋白酶体功能异常可能在帕金森发病机制中起重要作用。     

依达拉奉对脂多糖诱导的大鼠多巴胺能神经元变性保护作用的研究

目的探讨自由基清除剂依达拉奉对脂多糖(LPS)诱导的多巴胺能神经元变性的保护作用。方法18只大鼠随机分成3组:磷酸缓冲液(PBS)对照组、生理盐水+LPS组(生理盐水治疗组)和依达拉奉+LPS组(依达拉奉治疗组)。黑质内立体定向注射15μg(2μl)LPS或PBS,采用免疫组织化学方法观察注射后14d大鼠黑质酪氨酸羟化酶(TH)阳性细胞的数量以及小胶质细胞的形态学变化。结果与对照组相比,生理盐水治疗组TH阳性细胞数减少到对侧的16%(P<0.05),细胞突触也明显减少;依达拉奉治疗组TH阳性细胞数较生理盐水治疗组明显增多,为对侧的59%(P<0.05),部分突触存在。两治疗组小胶质细胞形态无明显差异。结论依达拉奉显著抑制LPS诱导的黑质多巴胺能神经元变性。     

凝血酶诱导的小胶质细胞激活促进多巴胺能神经元变性

目的探讨凝血酶（Thrombin）诱导小胶质细胞（Micoglia）激活与黑质多巴胺能神经元变性的关系。方法采用立体定向术注射凝血酶至大鼠黑质,在不同时间点观察酪氨酸羟化酶（tyrosine hydroxylase,TH）神经元的表达及小胶质细胞的激活情况;同时检测黑质NO量及iNOS mRNA表达。结果（1）凝血酶注入大鼠黑质导致明显的黑质多巴胺能神经元变性,呈时间依赖性,TH阳性细胞数在第3d开始下降,第7d有大量的TH阳性细胞丢失,与对照侧相比下降达约53％（P〈0．01）;高倍镜下可见胞体皱缩、突起明显缩短或减少;14d时细胞数下降至21％,30d时下降至12％（P〈0．01）。（2）凝血酶注射入黑质4h后小胶质细胞开始呈现为“灌木丛样”或少量呈现“阿米巴样”：12h后小胶质细胞数目明显增加且绝大部分呈现“阿米巴样”;24h后细胞已完全激活,“阿米巴样”细胞达高峰;3d维持高峰;14d后小胶质细胞染色变淡,体积变小,“阿米巴样”细胞数目下降。（3）与对照组相比,iNOSmRNA表达明显上调及NO合成增加（P〈0．05）,并且有iNOS在小胶质细胞表达。结论凝血酶对多巴胺能神经元具有一定的损毁作用,小胶质细胞的激活先于多巴胺能神经元变性,其激活后释放的NO有可能参与多巴胺能神经元变性。     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

腺垂体功能减退症临床特征变化分析

目的探讨腺垂体功能减退症患者的病因结构变化及临床表现。方法回顾性分析我院2013-01—2016-12住院及门诊78例腺垂体功能减退症患者的临床资料。结果男32例(41.03%),女46例(58.97%);诊断时年龄11~89岁,平均62.5岁;鞍区占位(包括术前及术后)52例(66.67%),席汉综合征8例(10.26%),空泡蝶鞍9例(11.65%),病因不明8例(10.26%),垂体-下丘脑发育不良1例(1.28%)。首次就诊科室:纳差厌食、恶心呕吐就诊于消化内科36例(46.15%)最常见。ACTH+TSH+Gn+G激素缺乏为19例最多,占24.36%,ACTH+TSH+Gn缺乏15例,占19.23%。结论腺垂体功能减退症病因结构发生变化,发病人群、首发症状及受累激素也不同,患者女性多于男性,发病年龄偏高,症状不典型,分布于临床多个科室,其中以低钠血症为首发临床表现就诊消化内科最多。     

Standards of instrumentation of EMG

Standardization of Electromyography (EMG) instrumentation is of particular importance to ensure high quality recordings. This consensus report on “Standards of Instrumentation of EMG” is an update and extension of the earlier IFCN Guidelines published in 1999. First, a panel of experts in different fields from different geographical distributions was invited to submit a section on their particular interest and expertise. Then, the merged document was circulated for comments and edits until a consensus emerged.The first sections in this document cover technical aspects such as instrumentation, EMG hardware and software including amplifiers and filters, digital signal analysis and instrumentation settings. Other sections cover the topics such as temporary storage, trigger and delay line, averaging, electrode types, stimulation techniques for optimal and standardised EMG examinations, and the artefacts electromyographers may face and safety rules they should follow. Finally, storage of data and databases, report generators and external communication are summarized.     

帕金森病运动症状进展分析

目的分析帕金森病(PD)患者运动症状进展特点。方法采用PD统一评分量表(UPDRS)Ⅲ对912例PD患者进行评估。结果与病程1年的患者比较,除病程1~2年的患者外,其他病程患者的UPDRSⅢ评分、强直分、姿势或步态异常分、轴性症状总分、言语分、步态分显著升高(均P0.05),病程5~6年及14年患者的震颤分,病程5~6年、7~8年、9~13年、14年患者的运动迟缓分、姿势分显著升高(P0.05~0.01)。轴性症状进展速度高于UPDRSⅢ评分。结论 PD患者病程早期UPDRSⅢ评分进展快,震颤症状进展独立于其他症状,轴性症状评分较UPDRSⅢ更敏感地反映疾病加重趋势。     

Frequency of accumulation of filaments in adaxonal cytoplasm of Schwann cells of myelinated fibers of rat spinal roots

Summary The frequency of accumulation of 6-nm filaments in the adaxonal cytoplasm of Schwann cells in the 6th lumbar dorsal and ventral roots was evaluated in 4-, 8-, 26- and 45-week-old Sprague-Dawley rats. The frequency was higher in 4- and 8-week-old (growing) rats than in 26- and 45-week old (mature) rats, and also higher in ventral than in dorsal roots in 4-, 8- and 26-week old rats. There were no clusters on certain groups of myelinated fibers according to the size of transverse axonal area, in both the ventral and dorsal roots. Therefore, this accumulation may reflect certain functions of the adaxonal cytoplasm of Schwann cell during natural growth and maturation of the axon and myelin sheath.     

Function of circle of Willis

Nearly 400 years ago, Thomas Willis described the arterial ring at the base of the brain (the circle of Willis, CW) and recognized it as a compensatory system in the case of arterial occlusion. This theory is still accepted. We present several arguments that via negativa should discard the compensatory theory. (1) Current theory is anthropocentric; it ignores other species and their analog structures. (2) Arterial pathologies are diseases of old age, appearing after gene propagation. (3) According to the current theory, evolution has foresight. (4) Its commonness among animals indicates that it is probably a convergent evolutionary structure. (5) It was observed that communicating arteries are too small for effective blood flow, and (6) missing or hypoplastic in the majority of the population. We infer that CW, under physiologic conditions, serves as a passive pressure dissipating system; without considerable blood flow, pressure is transferred from the high to low pressure end, the latter being another arterial component of CW. Pressure gradient exists because pulse wave and blood flow arrive into the skull through different cerebral arteries asynchronously, due to arterial tree asymmetry. Therefore, CW and its communicating arteries protect cerebral artery and blood–brain barrier from hemodynamic stress.     

Effects of prevention of afferentation of the development of the chick optic lobe

BONDY, S. C., M. E. HARRINGTON AND C. L. ANDERSON. Effects of prevention of afferentation on the developmentof the chick optic lobe. BRAIN RES. BULL. 3(5) 411–413, 1978.—The effects of unilateral extirpation of the right optic cup of the three-day incubated chick embryo upon the rate of synthesis and the stability of DNA in the non-innervated optic lobe, have been studied. This surgical procedure prevents innervation of the optic lobe contralateral to the removed eye, while the other optic lobe is normally innervated by retinal ganglion cells of the remaining eye. At the 20th day of incubation, the DNA content of the non-innervated lobe was below that of the paired lobe receiving normal innervation. This deficiency of cell number was caused by two events; death of an excess number of neurons formed early in embryogenesis and a reduced rate of glial proliferation in the later stages of incubation.     

Release of endogenous catecholamines from slices of hypothalamus of rats

The release of endogenous catecholamines from superfused slices of rat hypothalamus was studied under basal conditions and during release evoked by 40 mM K⁺. Catecholamines in superfusates, and in extracts of the tissue after stimulation, were isolated by column chromatography and quantitated by liquid chromatography with electrochemical detection. Norepinephrine (NE) was not consistently demonstrable in superfusate collected under basal conditions, but 40 mM K⁺ caused the release of from 2 to 4 ng/g of tissue per min. The addition of cocaine to the superfusate caused increases in basal and evoked release of NE. Epinephrine (E) could be measured in superfusates of slices from male but not female rats and then only when cocaine was added to the superfusate. Accordingly, the concentration of E in hypothalamus was greater in male rats than in female rats. Dopamine (DA) was not consistently measurable in the spontaneous overflow from slices either in the presence or absence of cocaine. K⁺-evoked release of DA could be demonstrated in slices from female rats. The addition of cocaine increased the evoked release of DA from slices from both sexes. Corticosterone, added to cocaine, had no effects on the efflux of any of the catecholamines. The experiments suggest that neuronal reuptake of all catecholamines is very efficient in the hypothalamus both under basal conditions and during evoked release.     

《绵阳市社会心理服务工作管理办法》解读

2018年,国家卫生健康委员会等10部委联合发布《关于印发全国社会心理服务体系建设试点工作方案的通知》,四川省绵阳市被列为全国第一批试点地区。绵阳市人民政府依据《中华人民共和国精神卫生法》等相关法律法规和文件精神,结合前期调查研究和社会心理服务工作的试点实际,编制出台了《绵阳市社会心理服务工作管理办法》,并于2021年12月25日起施行。本文围绕社会心理服务的相关概念、办法总则、重点内容、保障措施等方面进行解读,以期为社会心理服务工作的规范、持续和有效开展提供参考。     

阿立哌唑对精神分裂症患者生活质量的影响

目的:比较阿立哌唑与利培酮对精神分裂症患者生活质量的影响。方法:60例精神分裂患者随机平分为两组各30例,分别给予阿立哌唑和利培酮治疗。疗程8周。用生活质量综合评定问卷-74(GQOLI-74)、阳性与阴性症状量表(PANSS)及副反应量表(TESS)评定疗效及不良反应。结果:阿立哌唑与利培酮均能显著提高精神分裂症患者生活质量,但阿立哌唑在改善GQOLI-74总分、躯体健康及社会功能维度优于利培酮。结论:阿立哌唑治疗有利于提高精神分裂症患者生活质量。