中枢神经系统一氧化氮对大鼠的痛觉调制作用

以钾离子透入引起大鼠甩尾的电流强度(mA)作为痛反应指标,采用侧脑室微量注射L-精氨酸(L-Arg)、亚甲基蓝(MB)等,观察大鼠痛阈的变化,分析探讨中枢神经系统中一氧化氮(NO)对大鼠痛觉的调制作用.结果显示:大鼠侧脑室微量注射NO前体及供体物质L-Arg和硝普钠(SNP)均引起明显的痛敏效应.微量注射MB和L-NAME后大鼠痛阈升高非常显著.侧脑室微量注射MB和L-Arg混合液后,大鼠痛阈较单纯注射MB组表现出明显降低的趋势,但与L-Arg组相比大鼠痛阈升高明显.提示:提高中枢内NO水平具有明显的痛敏效应,而降低中枢神经系统NO水平表现显著镇痛作用.中枢神经系统NO对大鼠痛觉的调制作用至少部分是通过NO-cGMP途径实现的.     

大鼠尾核内一氧化氮对apelin受体mRNA表达的影响(英文)

目的研究大鼠尾核内一氧化氮(nitric oxide,NO)的作用机理及其与apelin 受体mRNA表达的相关性。方法大鼠尾核内微量注射NO前体L-精氨酸(L-Arg)、NG-硝基-L-精氨酸甲酯(NG-nitro-L-arginine methyl ester,L-NAME)和生理盐水(NS),应用逆转录 - 聚合酶链反应(RT-PCR)检测大鼠尾核给药 4、8、12、24 及 48 h 后一氧化氮合酶(neuronal nitric oxide synthase,nNOS) mRNA和apelin受体mRNA表达的变化及二者的相关性。结果注射L-Arg后大鼠尾核nNOS和apelin受体的mRNA表达明显升高,注射L-NAME后大鼠尾核nNOS和apelin受体mRNA表达明显降低,且均有统计学意义。注射L-Arg和L-NAME后,nNOSmRNA和apelin受体mRNA的表达呈正相关。结论在中枢神经系统,尤其是在尾核中,NOS的活性是NO作为神经递质或调质参与包括中枢痛觉调制作用在内的多种生物学作用的关键因素之一,尾核内NO的神经生物学作用可能与apelin受体作用相关 。     

L-NAME抗C6胶质瘤细胞增殖的体外研究

一氧化氮 (NO)对实体肿瘤具有促进生长作用 ,但它对离体肿瘤细胞生长、分化作用尚存在争议。该实验通过体外培养 C6细胞株检测应用 NO合酶 (NOS)抑制剂 N-硝基精氨酸甲酯 (L-NAME)对其生长的影响。1　材料和方法　取对数生长期细胞 ,加 0 .2 g/ L EDTA-1 .2 5 g/ L 胰蛋白酶 (1     

大鼠尾核内一氧化氮对apelin受体mRNA表达的影响

目的研究大鼠尾核内一氧化氮（nitric oxide,NO）的作用机理及其与apelin受体mRNA表达的相关性。方法大鼠尾核内微量注射NO前体L-精氨酸（L-Arg）、N^G-硝基-L-精氨酸甲酯（N^G-nitro-L-arginine methyl ester,L-NAME）和生理盐水（NS）,应用逆转录-聚合酶链反应（RT-PCR）检测大鼠尾核给药4、8、12、24及48h后一氧化氮合酶（neuronal nitric oxide synthase,nNOS）mRNA和apelin受体mRNA表达的变化及二者的相关性。结果注射L-Arg后大鼠尾核nNOS和apelin受体的mRNA表达明显升高,注射L-NAME后大鼠尾核nNOS和apelin受体mRNA表达明显降低,且均有统计学意义。注射L-Arg和L-NAME后,nNOSmRNA和apelin受体mRNA的表达呈正相关。结论在中枢神经系统,尤其是在尾核中,NOS的活性是NO作为神经递质或调质参与包括中枢痛觉调制作用在内的多种生物学作用的关键因素之一,尾核内NO的神经生物学作用可能与apelin受体作用相关。     

L-精氨酸枕大池注射对蛛网膜下腔出血脑血管痉挛的影响

目的:研究L-精氨酸枕大池注射对兔蛛网膜下腔出血后脑血管痉挛的影响及作用机制。方法:采用双侧颈动脉结扎及枕大池二次注血法制造兔蛛网膜下腔出血模型。在蛛血后第4天,以比色法测定血清及脑脊液中NO及脑组织NOS的含量。光镜下测定基底动脉的动脉壁厚度和基底动脉的内径,以其比值作为脑血管痉挛的指标。治疗组分为300μmol及500μmol组,在蛛血后第4天,枕大池持续微泵滴注L-精氨酸,在滴注后再分别测定上述指标。结果:蛛血后第4天,基底动脉的动脉壁厚度和内径的比值明显升高,血清及脑脊液中NO及脑组织NOS的含量降低。在L-精氨酸滴注后,脑血管痉挛缓解。血清及脑脊液中NO及脑组织NOS的含量较对照明显升高。结论:L-精氨酸枕大池注射对兔蛛网膜下腔出血后的血管痉挛具有治疗作用。L-精氨酸可能是通过NO及NOS系统起作用。     

抑郁症患者血浆精氨酸加压素与促肾上腺皮质激素增高的关系

目的:探讨精氨酸加压素(AVP)的功能变化在抑郁症发生中的作用. 方法:应用化学发光免疫分析法和酶联免疫法测定83例抑郁症患者、57例正常对照者的血浆促肾上腺皮质激素(ACTH)、AVP和皮质醇(Cor)浓度水平. 结果:抑郁症组血浆ACTH浓度(48±30) ng/L、Cor浓度( 188±59) μg/L分别高于正常对照组(18 ±7) ng/L、( 165±55)μg/L,差异有统计学意义(t=9.422,P＜0.01;t =2.453,P＜0.05);抑郁症组血浆AVP浓度(6.0±5.7) ng/L与对照组(4.5±2.6) ng/L差异无统计学意义(t=1.849,P＜0.05).ACTH异常的(ACTH≥50ng/L)抑郁症患者AVP、Cor浓度[(8.0±7.0)ng/L,(211±55) μg/L]高于ACTH正常的(ACTH＜ 50 ng/L)抑郁症患者[(3.5±3.2) ng/ml,( 174±58)μg/L],差异有统计学意义(t=2.728,t =3.027,P均＜0.01).抑郁症患者的AVP与ACTH存在正相关(r=0.286,P=0.027),ACTH与Cor存在正相关(r=0.455,P=0.000). 结论:ACTH水平增高的抑郁症患者AVP异常,AVP调节功能可能是影响抑郁症疾病过程的一个因素.     

L-精氨酸对偏头痛患者血浆一氧化氮、内皮素含量的影响及临床意义

目的　探讨L -Arg对偏头痛患者血浆NO、ET含量变化的影响及其临床意义 ,为防治偏头痛的发生发作提供依据。方法　NO测定采用分光光度法 ,ET用放射免疫法。结果　偏头痛患者血浆NO、ET含量均高于对照组 ,两组注射L -Arg与未注射L -Arg血浆NO含量有非常显著性差异 (P<0 .0 1) ,而ET基本无变化。结论　偏头痛发生发作可能与L -Arg/NO通路活动增强有关 ,L -Arg增加抑制血管内皮细胞释放ET是偏头痛加剧的因素之一。     

L—NA对大鼠学习记忆的影响及NO、SS相关性研究

目的 探讨一氧化氮（NO）和生长抑素（SS）在学习记忆过程中的作用及相互作用。方法 大鼠海马微量注射一氧化氮合酶（NOS）抑制剂N-ω硝基－L精氨酸（N-ω－Nitro-L-Arginine,L-NA) 后采用Y型电迷宫观察大鼠学习记忆能力的改变,以硝酸还原酶法测定海马NO含量,以放射免疫法测定海马SS含量,并进行学习记忆能力、NO含量和SS含量相关性分析。结果 海马微量注射L－NA组大鼠与生理盐水对照组和正常对照组比较,海马中NO、SS含量明显下降（P＜0．01）。Y型电迷宫测定次数明显增加（P＜0．01）,L－NA组大鼠海马NO水平和SS水平呈显著正相关,NO、SS水平均与Y型电迷宫测试次数呈显著负相关。结论 海马中NO、SS水平的正常是机体实现正常学习和记忆过程的重要因素;NO可能通过调节SS的合成和释放,共同促进学习和记忆过程。     

SB-271046对匹罗卡品致痫大鼠空间学习记忆的影响

目的观察5-羟色胺6受体拮抗剂SB-271046对匹罗卡品致痫大鼠空间学习记忆的作用效应。方法成年雄性SD大鼠分为两组:空白对照组(Vehicle组,n=10),氯化锂-匹罗卡品组(Lithium chloride-Pilocarpine,LiCl-PILO组,n=40)。首先根据注射LiCl-PILO后是否出现癫痫持续状态(Status Epilepticus,SE),出现SE者纳入实验,未出现SE和死亡者则剔除;然后再随机分为3组:模型组即侧脑室注射羟丙基-β-环糊精(Hydroxypropyl-β-cyclodextrine,HP-β-CD),4μl;药物组按不同剂量分为2组,即侧脑室注射N-[4-Methoxy-3-(4-methyl-1-piperazinyl)-phenyl]-5-chloro-3-methylbenzo-thiophene-2-yl-sulphonamide monohydrochloride(SB-271047)剂量为10μg,4μl和侧脑室注射SB-271046剂量为20μg,4μl。结果在Y迷宫自主交替行为实验中,模型组自主交替率显著下降(P0.01),药物组显著提高尤其是20μg剂量组(P0.05)。在Y迷宫新奇事物探索实验中,模型组的新臂时间比显著下降(P0.01),药物组有提高趋势(P0.05)。在Morris水迷宫定位航行实验中,模型组平均潜伏期延长显著延长(P0.01),药物组明显缩短尤其是20μg剂量组(P0.05)。在Morris水迷宫空间探索实验中,模型组平均潜伏期延长,穿越平台次数减少,原平台象限停留时间缩短(P0.05),药物组有改善趋势(P0.05)。结论 SB-271046可以改善癫痫大鼠的空间学习记忆,主要作用于记忆获得巩固阶段,20μg剂量作用明显。     

L-精氨酸及氧对颅高压后神经源性肺水肿的影响

目的 探讨L-精氨酸（L-Arg）及氧对神经源性肺水肿的影响。方法 40只家兔随机分为:A组（n=10）颅高压未吸氧;B组（n=10）颅高压吸氧;C组（n=10）颅高压吸氧并静脉注射L-Arg;对照组（n=10）。行平均动脉压（MAP）、左心房压（LAP）、肺动脉压（PAP）及肺血管阻力（PVR）监测;肺循环血浆NO;肺血管外水量（EVLW）测定及组织学检查。结果 与A组比较B组PAP、PVR明显降低（P<0.01）,肺循环血浆NO无明显升高,EVLW低于A组但高于对照组;C组肺循环血浆NO明显高于其他各组,EVLW无明显增加,电镜毛细血管基底膜基本完整。结论 L-Arg使内源性NO增加,在氧的协同作用下使PAP、PVR降低,维持了肺血管内皮细胞完整性。     

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.     

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.     

Gender in Voice Perception in Autism

Deficits in the perception of social stimuli may contribute to the characteristic impairments in social interaction in high functioning autism (HFA). Although the cortical processing of voice is abnormal in HFA, it is unclear whether this gives rise to impairments in the perception of voice gender. About 20 children with HFA and 20 matched controls were presented with voice fragments that were parametrically morphed in gender. No differences were found in the perception of gender between the two groups of participants, but response times differed significantly. The results suggest that the perception of voice gender is not impaired in HFA, which is consistent with behavioral findings of an unimpaired voice-based identification of age and identity by individuals with autism. The differences in response times suggest that individuals with HFA use different perceptual approaches from those used by typically developing individuals.     

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.     

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.     

Progress in neuroprotection in Parkinson's disease

Slowing or aborting the progress of neurodegeneration in Parkinson's disease (PD) remains the most important unmet need of this disorder. There are several recent developments in trial design and also in drugs under investigation for possible neuroprotective effect. Emphasis has been placed on clinical as opposed to imaging end-points and these include change in a clinical rating scale, e.g. United Parkinson's disease Rating Scale (UPDRS), or time to additional therapy. The introduction of the delayed-start, or wash-in, trial design adds an additional dimension to drug evaluation for neuroprotection. Compounds that have been recently tested in clinical trial include the monoamine oxidase-B inhibitor rasagiline, the anti-apoptotic agents TCH346 and CEP1347, and the promitochondrial agent creatine. The dopamine agonists have been evaluated for a neuroprotective effect using imaging end-points. Perhaps the most important and simplest concept for neuroprotection has been the theory that early dopaminergic support for the degenerating dopaminergic system per se provides significant long-term clinical benefit for PD patients.     

Changes in parasympathetic system in medulla oblongata in male pigs in the course of tachycardia-induced cardiomyopathy

Background

Autonomic imbalance constituting a fundamental feature of heart failure (HF) has been assessed mainly at the periphery. Changes in the functioning of autonomic centers in the brain remain unclear. We investigated the molecular elements of parasympathetic system, i.e. α7 nicotinic acetylcholine receptor (α7nAChR) and enzymes metabolizing acetylcholine (acetylcholinesterase, AChE, choline acetyltransferase, ChAT) in medulla oblongata (MO) of male pigs with chronic tachycardia-induced cardiomyopathy.

Methods

The mRNA levels of AChE, ChAT, α7nAChR and X-box binding protein 1 (spliced form, XBP1s) in MO were analyzed using qPCR, AChE and ChAT activities using spectrophotometry, proteasome activity using fluorometry, and the protein level of α7nAChR using Western blotting.

Results

The development of systolic HF was accompanied by an increase in circulating catecholamines, a decrease in the AChE and α7nAChR mRNA in MO, an increase in AChE activity (all p < 0.05), and no change in either the mRNA or activity of ChAT. Both circulating catecholamine levels and AChE activity were inversely related to systolic function of left myocardial ventricle (p < 0.05). The level of α7nAChR protein in MO and its cytoplasmatic fraction were higher in pigs with moderate and severe HF as compared to the other animals (p < 0.01). There was no difference in proteasome activity in MO between diseased and healthy animals, whereas the XBP1s mRNA decreased during HF progression (p < 0.05).

Conclusions

Molecular elements of parasympathetic system are changed within the medulla oblongata during the progression of systolic non-ischemic heart failure in male pigs, indicating a functional link between MO and heart in HF.