重组人粒细胞集落刺激因子对大鼠脑缺血再灌注损伤脑组织NF-κB和iNOS表达的影响

目的探讨重组人粒细胞集落刺激因子(rhG-CSF)在大鼠脑缺血再灌注损伤中的神经保护机制。方法将健康成年雄性SD大鼠随机分为假手术组、模型组和rhG-CSF治疗组(治疗组),每组12只。用Longa线栓法制作大鼠大脑中动脉缺血模型,治疗组于脑缺血后2h实施再灌注并予rhG-CSF(50μg/kg)腹部皮下注射,假手术组和模型组给予等量生理盐水。采用Longa 5分制评分标准进行神经功能缺损评分,免疫组化法(PV-6001二步法)检测各组大鼠脑组织中核转录因子-κB p65(NF-κB p65)和诱导型一氧化氮合酶(iNOS)表达水平,2,3,5-三苯基氯化四氮唑(TTC)染色法测定脑梗死体积。结果模型组与治疗组大鼠均可见大脑中动脉供血区梗死灶,治疗组大鼠脑梗死体积〔(24.04±1.49)%〕较模型组〔(31.05±1.49)%〕减小(t=8.12,P<0.01),治疗组神经功能评分(1.25±0.45)低于模型组(2.58±0.67)(U=12.00,P<0.01);治疗组NF-κB p65、iNOS表达的灰度值〔分别为(136.18±5.26)、(128.05±3.19)〕均较模型组〔分别为(96.67±3.94)、(109.73±6.07)〕增高(分别t=-39.51、P<0.01,t=-18.31、P<0.01);假手术组大鼠脑组织未发现梗死灶,脑组织内NF-κB和iNOS表达的灰度值〔分别为(161.86±4.27)、(163.99±4.08)〕高于模型组(分别t=65.20、P<0.01,t=54.26、P<0.01)。结论 rhG-CSF对脑缺血再灌注损伤具有神经保护作用,其机制可能与降低NF-κB p65、iNOS表达,抑制炎性反应有关。     

阿魏酸钠对慢性脑缺血大鼠的神经保护作用机制研究

目的探讨阿魏酸钠对慢性脑缺血大鼠的神经保护作用及其机制。方法以双侧颈总动脉结扎(2-VO)法制备慢性脑缺血模型,于术后6周分别给予阿魏酸钠和PBS干预,分为阿魏酸钠干预组和模型对照组。另设假手术组(仅分离双侧颈总动脉,但不结扎)作为空白对照。术后8周行Morris水迷宫实验,评价大鼠的空间学习记忆功能,同时观察双侧颞叶内侧缺血区脑组织血管密度、激光共聚焦法检测毛细血管内径、缺血边界地区的毛细血管分支点数目和微血管总面积等指标、海马细胞增殖情况(免疫组化法)和血浆血管内皮生长因子(VEGF)水平(ELISA法检测),以探讨其可能的机制。结果 Morris水迷宫结果显示,阿魏酸钠干预组第2、3、4、5天逃避潜伏期[分别为(43.55±6.34)s、(38.11±1.20)s、(34.75±5.30)s、(24.39±3.93)s]明显短于模型对照组[分别为(50.89±6.31)s、(43.72±8.21)s、(50.79±9.36)s、(44.39±3.93)s,均P0.01];阿魏酸钠干预组第一象限游泳时间明显长于模型对照组[分别为(27.36±3.89)s、(14.68±2.36)s,P=0.002]。阿魏酸钠干预组毛细血管内径与模型对照组比较变短[分别为(3.02±0.21)μm、(3.35±0.18)μm,P=0.003],阿魏酸钠干预组缺血边界地区的毛细血管分支点数目与模型对照组同源组织区比较显著增加(分别为205.80±12.70、158.42±10.92,P=0.001),0.002mm3体积内阿魏酸钠干预组微血管总面积与模型对照组比较明显增加[分别(83389±4026)μm2、(73349±3986)μm2,P=0.004]。阿魏酸钠干预组缺血脑组织内的BrdU阳性细胞数明显高于模型对照组(分别为23.82±3.05、10.26±2.89,t=18.26,P=0.004)。阿魏酸钠干预组VEGF水平明显高于模型对照组[分别为(67.58±9.61)pg/mL、(21.90±5.16)pg/mL,P=0.008]。结论阿魏酸钠可以显著改善慢性脑缺血大鼠的空间学习记忆能力,其机制可能与VEGF介导的血管密度增加有关。     

黄芪注射液对大鼠红核神经元逆行溃变的影响

目的探讨黄芪注射液对大鼠红核神经元逆行溃变的影响。方法将48只SD大鼠随机分为4组:正常组、假手术组、实验组和模型对照组,每组12只。假手术组在脊髓C3、C4之间切开黄韧带。实验组和模型对照组在脊髓C3、C4之间外侧索横断损伤红核脊髓束,随后分别以黄芪注射液和生理盐水进行腹腔注射。4周后,各组取6只大鼠将轴突示踪剂生物素葡聚糖胺(BDA)注入红核进行顺行示踪,检测轴浆顺行运输能力;另外6只大鼠行尼氏染色显示红核神经元形态及数目。结果实验组和模型对照组被BDA标记轴突的相对面积及数目低于正常组或假手术组(均P0.01),实验组被BDA标记轴突的相对面积及数目明显高于模型对照组(均P0.01);实验组和模型对照组存活的红核神经元数目和平均截面积均低于正常组或假手术组(均P0.01),实验组的红核神经元数目和平均截面积均高于模型对照组(均P0.01)。结论黄芪注射液可通过改善轴浆运输能力,提高胞体的存活率,从而对逆行溃变的红核神经元具有保护作用。     

再程序化脂肪干细胞移植治疗大鼠脊髓损伤的机制

目的制备再程序化脂肪干细胞(ADSCs),并在体研究再程序化ADSCs移植入大鼠脊髓损伤模型后促进损伤脊髓神经功能恢复的作用和机制。方法体外培养、纯化和鉴定大鼠ADSCs,并利用慢病毒包装神经元生成素2(Ngn2)基因转染ADSCs制备再程序化干细胞。体内实验将48只雌性SD大鼠随机分成3组:SCI对照(A)组、单纯ADSCs移植(B)组和Ngn2-ADSCs移植(C)组。采用BBB评分评价大鼠运动功能,并通过HE染色、免疫组化和免疫荧光等方法检测脊髓组织学改变和相关蛋白的表达水平,进而观察实验动物脊髓功能恢复情况。结果 Ngn2-ADSCs移植组在运动功能评分、胶质瘢痕的形成、脊髓损伤后病理变化和分泌神经营养因子BDNF和VEGF蛋白含量明显优于其他组。结论 Ngn2-ADSCs移植后能有效地存活,并分化为神经细胞,抑制胶质瘢痕形成,减小脊髓损伤空洞,增加BDNF和VEGF表达,最终促进SCI大鼠的运动功能恢复,较单纯应用ADSCs能更好地促进SCI修复。     

运动神经元病患者的肛门外括约肌肌电图特征

目的总结运动神经元病(motor neuron disease,MND)患者的肛门外括约肌肌电图(EAS-EMG)特点。方法分析20例不同临床亚型MND患者的EAS-EMG资料,并与无二便障碍症状和体征的阴性对照组(对照组)对比。结果与对照组〔(12.21±2.26)ms、(512.89±363.55)(ms.μV)〕比较,MND患者的肛门外括约肌(EAS)运动单位电位(motor unit potential,MUP)平均时限延长〔(14.55±2.27)ms,P=0.000〕,面积增大〔(718.47±236.57)(ms.μV),P=0.05〕,MUP波幅、多相波比例、平均相在两组间无统计学差异(P>0.05)。结论 MND患者EAS存在临床下神经源性损害,MUP时限、面积是反映MUP特征的敏感指标。     

NG2细胞的增殖活化对大鼠脊髓损伤后神经病理性疼痛产生和维持的影响

目的探讨NG2细胞在脊髓损伤(SCI)后神经病理性疼痛的产生和维持中的作用。方法将100只健康成年雄性SD大鼠按随机数字表法分为对照组(n=20, 不做任何干预措施)、假手术组(n=40, 暴露T10节段但不实施脊髓撞击)及SCI组(n=40, 暴露T10节段并采用改进型Allen’’s法构建SCI模型)。分别于术前1 d及术后14 d、21 d、28 d时, 应用Von Frey纤维探针检测大鼠后肢的机械缩足反射阈值(MWT), 采用免疫荧光染色检测大鼠脊髓背角NG2阳性细胞数量占细胞总数比例, 应用Western blotting实验检测大鼠脊髓背角硫酸软骨素蛋白多糖(CSPG)的表达。结果术后14 d、21 d、28 d时, SCI组大鼠后肢MWT均明显低于对照组及假手术组, 脊髓背角NG2阳性细胞数量占细胞总数比例均明显高于对照组及假手术组, 脊髓背角CSPG表达均明显高于对照组及假手术组, 差异均有统计学意义(P<0.05)。SCI组大鼠术前1 d及术后14 d、21 d、28 d时的后肢MWT呈现先下降后回升趋势, 脊髓背角NG2阳性细胞数量占细胞总数比例呈现先上升后...     

HCV感染诱导BV-2细胞TNF-α分泌与TLR2 mRNA表达的关系

目的探讨丙型肝炎病毒(HCV)感染后小鼠小胶质细胞(BV-2)上清液中TNF-α水平与Toll样受体2(TLR2)mRNA表达的相关性,为进一步探讨TLR2介导的小胶质细胞抗HCV的免疫机制提供依据。方法将BV-2细胞分为空白对照组(常规培养用DMEM高糖培养液)、正常血清对照组〔常规培养用含有20%(体积分数)正常血清的DMEM高糖培养液〕及实验组〔常规培养用含有20%(体积分数)HCV阳性血清的DMEM高糖培养液〕,分别以ELISA方法检测各组HCV感染后3、6、9 h的BV-2细胞培养上清液中的TNF-α水平,以RT-PCR法检测同组相同时间点BV-2细胞TLR2 mRNA表达变化,并分析两者的相关性。结果空白对照组与正常血清对照组相同时间点TLR2 mRNA表达及TNF-α水平比较无统计学差异(P>0.05)。实验组3、6、9h TNF-α水平分别为(144.67±5.51)(、168.33±3.06)、(185.50±4.82)pg/mL,均高于两对照组〔空白对照组分别为(43.17±1.79)(、44.23±2.13)、(45.61±2.38)pg/mL、正常血清对照组分别为(43.33±1.97)、(43.34±1.55)(、48.08±2.24)pg/mL〕(均P<0.05);实验组3、69、h时TLR2 mRNA表达水平分别为1.08±0.061、.42±0.05、1.61±0.57,各时间点间比较有统计学差异(P<0.05),实验组69、h与3 h比较有统计学差异(P<0.05),但9 h时与6 h时比较无统计学差异(P>0.05)。Pearson相关分析显示TLR2 mRNA表达与TNF-α分泌水平呈正相关(r=0.819,P<0.01)。结论 HCV感染后TLR2表达及TNF-α水平均明显增高,两者可能参与了BV-2细胞抗HCV的免疫过程。     

直流电场治疗脊髓损伤的实验研究

目的 通过开展直流电场治疗脊髓损伤的实验研究,以证实其疗效并为临床提供依据。方法 ２４只中国家犬随机分成３组,用Ａｌｌｅｎ ＷＤ法致脊髓完全损伤,再置入电刺激器,观察伤后１、２、３个月神经功能、皮层体感诱发电位、神经元数量、神经元截面积和尼氏体密度恢复情况。结果 伤后立即置入电刺激器（Ｂ组）及脊髓损伤后６小时再置入电刺激器（Ｃ组）上述各项指标均优于同时期对照组（Ａ组）（Ｐ〈０．０５或Ｐ〈０．０１）     

大鼠脊髓损伤后Nogo-A表达变化的免疫组织化学研究

目的观察大鼠脊髓损伤后不同时间点Nogo—A蛋白在脊髓的表达变化。方法大鼠分脊髓损伤组、假手术组和正常对照组。损伤动物存活1d、3d、7d后，分别进行Nogo—A抗体的免疫组织化学染色。结果损伤部位的灰质神经元和白质少突胶质细胞均呈明显的Nogo—A免疫阳性反应，随着损伤后存活时间的延长，两者的阳性反应细胞相对染色强度及数量均逐渐下降。结论脊髓损伤后，Nogo—A在灰质神经元有表达，其表达相对强度和表达细胞数量先明显增加，随后逐渐减少，与少突胶质细胞的表达变化相似。     

Neuroimaging in epilepsy in tropics

Epilepsy is a major public health problem in many tropical countries. Also, some of the tropical diseases are major contributors to the higher prevalence of epilepsy in these countries. The etiologic factors responsible for epilepsy in these countries are quite different from those in the developed world. This article discusses the etiologic factors and neuroimaging of epilepsy in light of the conditions in these tropical countries.     

癫痫与抑郁关系的研究进展

抑郁是癫痫患者中常见的精神障碍,严重地影响了患者的生活质量。传统的观点认为癫痫患者因为存在着诸多社会学问题易出现抑郁倾向,癫痫和抑郁是单向的联系,但大量的研究已经证明癫痫和抑郁之间存在双向的联系,一种异常状态的存在可能易转化为另一种异常状态的发展。癫痫和抑郁存在着共同的发病机制。本文主要就癫痫和抑郁的双向联系以及抗抑郁药物在癫痫患者中的应用进行阐述。     

Sudanophilic lipid accumulation in astrocytes in periventricular leukomalacia in monkeys

Summary Sudanophilic lipid accumulation is a characteristic feature of periventricular leukomalacia (PVL) of infants. At least two types of lipid-containing cells have been identified, one being the macrophage, the other the pre-myelin glial cell. A third type of lipid-containing cell has been seen in two monkeys with spontaneous PVL. Electron microscopically this cell appears to be an astrocyte. This probably represents a reaction of the astrocyte to hypoxia and may be the equivalent of the hypertrophic astrocytes found in human infants.Supported in part by NIH grant HDO 8633 and the Regional Primate Research Center Grant RR-00166     

Increase in cathepsin D activity in rat brain in aging

Cathepsin D-like activity in homogenates of five brain areas of 3-month-old and 24-month-old Fischer 344 rats was measured. With hemoglobin as substrate at pH 3.2, more than 90% of the activity was inhibited by pepstatin. In each area studied, activity was more than twice as high in the old rat brain: 140-160% higher in the cortex, cerebellum, pons-medulla, and striatum and 90-100% higher in the hippocampus and spinal cord. The greatly increased metabolic capacity in the absence of an increase in protein turnover may have a role in age-related pathological degeneration in the brain.     

Increase in noradrenaline-synthesizing enzyme activity in medulla oblongata in Parkinson's disease

Summary Dopamine beta hydroxylase (DBH), the noradrenaline-synthesizing enzyme, and phenylethanolamine-N-methyltransferase (PNMT), the adrenaline-synthesizing enzyme, were assayed in 18 areas of brain stem in eight cases of parkinsonian syndromes and of four age- and postmortem delay-matched controls. Dissection was performed by the punch technique and enzyme activities assayed by radiometric methods. No significant change was found for PNMT activity. DBH activity was significantly increased in the A2-C2 area of the medulla oblongata (including the nucleus tractus solitarius) in the cases of Parkinson's disease.The A2-C2 area is known to be implicated in the control of blood pressure in rats. These findings are discussed in relation to orthostatic hypotension and the influence ofl-dopa therapy.Supported by grants from INSERM ATP 657897, ATP 8179113, CRL 79-1-356-6, DGRST (80 E 0882), FRMF, and Sandoz-France France     

Issues in evaluation of cognition in the elderly in developing countries

Background:

Developing regions of the world host the majority of elderly subjects who are at risk for dementia. Reliable epidemiological data from these countries is invaluable in tackling this global problem. Scarcity of such data in literature is largely attributable to problems that are unique to developing communities worldwide.

Objective:

To classify and describe the problems that interfere with the collection of reliable epidemiological data on cognitive impairment in the elderly in developing communities, and to suggest practical solutions for some of them.

Methods:

Inferring from the experiences of a large, ongoing, population-based study on the cognitive impairments in the elderly in South India and from the review of literature.

Conclusion:

A fatalistic attitude regarding aging in the communities, significant heterogeneity in educational abilities and activities of daily living, high illiteracy among rural subjects, and lack of an organized health care system and updated demographic figures are some of the major factors that contribute to technical, namely, methodology-related problems and practical, namely, subject-related problems in such epidemiological studies.     

Suicide in the elderly in Austria

In most countries men and women have the highest suicide rates in age groups over 60 years. We investigated suicide rates for the elderly in Austria, a country with one of the highest suicide rates in the world, for the period 1980–1991, using data from the Federal Statistical Division. Suicide rates remained stable over the last decade at a very high level. The mean rate for men was 85.2, for women 28.6/100 000. In men and women rates rise with age. The mean rate of men rises from 51.2 (60–64 years) to 117.3/100 000 (over 85 years); in women there is an increase from 21.4 (60–64 years) to 32.8/100 000 (over 85 years). We did not confirm findings in other countries, where suicide rates have increased in recent years.     

Characteristics of nociceptors in the periodontium--an in vitro study in rats

Recent studies have indicated that nociceptors can be classified into various types according to their physiological properties. These studies have clarified that the frequency distribution of various nociceptor types is different among body sites and animal species. In the present study, we investigated the physiological properties of rat's periodontal nociceptors in an in vitro jaw-nerve preparation. Responses were recorded from functional single filaments in the inferior alveolar nerve. To determine the nociceptor type, calibrated von Frey filaments, heat, and bradykinin (BK) stimuli were used. We found five subtypes of nociceptors in the periodontal ligaments of the lower incisor: Adelta-high threshold mechanonociceptors (Adelta-HTM, n=28), Adelta-mechanoheat nociceptors (Adelta-MH, n=6), Adelta-polymodal nociceptors (Adelta-POLY, n=26), C-high threshold mechanonociceptors (C-HTM, n=3) and C-polymodal nociceptors (C-POLY, n=4). Most nociceptors were Adelta-innervated, while only a small number of C-innervated nociceptors were found. The present results suggest that periodontal nociceptors transmit mainly fast pain, and may thus play a role in rapid detection of injure-related stimuli during mastication.     

Ethnic disparities in problem behaviour in adolescence contribute to ethnic disparities in social class in adulthood

BACKGROUND: It is important for prevention of social class disparities to know how ethnic disparities in social class arise among migrant children. We contribute to this understanding by examining the role of problem behaviour in adolescence. METHODS: Prospective observational study with 753 Dutch native and 217 Turkish migrant adolescents (11-18 year) followed for 10 years. Internalising and externalising problems were assessed in adolescence and employment status and occupational level were assessed in adulthood. The difference in odds ratios (OR) before and after adjustment for internalising and externalising problems was an indication of the predictive value of disparities in internalising and externalising problems for the development of social class disparities. RESULTS: A total of 135 (62%) of the Turkish and 602 (80%) of the Dutch adults were employed. Internalising and externalising problems were not associated with employment status. Of the employed, 65 (48%) Turkish and 179 (30%) Dutch adults worked in low-level occupations (p < 0.0001). Internalising and externalising problems were associated with both ethnicity and occupation. The OR for low-level occupation for Turkish adults was 1.78 (1.19-2.65), indicating ethnic disparities. Adjustment for internalising problems lowered the OR with 36% to 1.50 (0.97-2.31), and adjustment for externalising problems lowered it with 8% to 1.72 (1.15-2.57). Findings were similar for men and women and did not vary by age. CONCLUSIONS: Ethnic disparities in occupational level in adulthood could partly be attributed to disparities in mental health between Turkish migrants and Dutch natives in adolescence. Prevention of ethnic disparities in mental health at young age may therefore also contribute to the prevention of occupational differences in adulthood.     

Defects in Bioenergetic Coupling in Schizophrenia

Synaptic neurotransmission relies on maintenance of the synapse and meeting the energy demands of neurons. Defects in excitatory and inhibitory synapses have been implicated in schizophrenia, likely contributing to positive and negative symptoms as well as impaired cognition. Recently, accumulating evidence has suggested that bioenergetic systems, important in both synaptic function and cognition, are abnormal in psychiatric illnesses such as schizophrenia. Animal models of synaptic dysfunction demonstrated endophenotypes of schizophrenia as well as bioenergetic abnormalities. We report findings on the bioenergetic interplay of astrocytes and neurons and discuss how dysregulation of these pathways may contribute to the pathogenesis of schizophrenia, highlighting metabolic systems as important therapeutic targets.