白藜芦醇对戊四氮致痫大鼠脑脊液、血清S1OOB蛋白的影响

目的 研究白藜芦醇(Res)对戊四氮致痫大鼠脑脊液、血清S100B蛋白的影响.方法 采用戊四氮(PTZ)腹腔注射建立慢性癫痫模型,造模成功后予以Res(15 mg/kg·d)灌胃干预10 d;采用酶联免疫吸附法测定脑脊液、血清S100B蛋白含量,海马标本行Nissl染色.结果 经28 d连续给药,18只大鼠符合Racine点燃标准,Res干预组大鼠痫性发作潜伏期明显延长,且发作时间明显低于癫痫模型组、二甲基亚砜组(P＜0.05).海马Nissl染色提示Res干预对大鼠海马CA1、CA3区神经元有保护作用(P＜0.05),而对齿状回保护作用不明显(P＞0.05).Res干预组大鼠脑脊液、血清S100B蛋白含量低于癫痫模型组、二甲基亚砜组(P＜0.05).结论 Res降低PTZ致痫大鼠脑脊液、血清S100B蛋白含量,或许减缓癫痫发作脑损伤发挥神经保护作用.     

白藜芦醇对戊四氮致痫大鼠脑脊液、血清S100B蛋白的影响

目的研究白藜芦醇（Res）对戊四氮致痫大鼠脑脊液、血清S100B蛋白的影响。方法采用戊四氮（PTZ）腹腔注射建立慢性癫痫模型,造模成功后予以Res（15mg／kg·d）灌胃干预10d;采用酶联免疫吸附法测定脑脊液、血清S100B蛋白含量,海马标本行Nissl染色。结果经28d连续给药,18只大鼠符合Racine点燃标准,Res干预组大鼠痫性发作潜伏期明显延长,且发作时间明显低于癫痫模型组、二甲基亚砜组（P〈0．05）。海马Nissl染色提示Res干预对大鼠海马CAl、CA3区神经元有保护作用（P〈0．05）,而对齿状回保护作用不明显（P〉0．05）。Res干预组大鼠脑脊液、血清S100B蛋白含量低于癫痫模型组、二甲基亚砜组（P〈0．05）。结论Res降低PTZ致痫大鼠脑脊液、血清SIOOB蛋白含量,或许减缓癫痫发作脑损伤发挥神经保护作用。     

新生期大鼠惊厥发作后血清神经元特异性烯醇酶、S100蛋白的动态变化及其意义

目的探讨新生期大鼠惊厥发作后血清神经元特异性烯醇酶(NSE)、S100蛋白(S100B)的动态变化及其意义。方法 80只新生期SD大鼠随机分为单次对照组(8只)、反复对照组(8只)和单次惊厥组(32只)、反复惊厥组(32只)。新生大鼠惊厥模型采用三氟乙醚诱导法建立。采用ELISA法测定各组大鼠血清NSE、S100B水平。结果单次惊厥组新生期大鼠致痫后12 h、24 h时血清NSE水平均明显高于单次对照组(P0.05~0.01)。反复惊厥组新生期大鼠致痫后12 h、24 h、48 h血清NSE水平均明显高于反复对照组(P0.05~0.01)。单次惊厥组新生期大鼠致痫后24 h时血清S100B明显高于单次对照组(P0.01)。反复惊厥组新生期大鼠致痫后12 h、24 h、48 h时血清S100B水平均明显高于反复对照组(P0.05~0.01)。结论NSE、S100B是新生期惊厥性脑损伤敏感生化指标,反复惊厥更易造成脑损伤。     

致痫后雌性大鼠血清及海马雌二醇和孕烯醇酮水平的动态变化

目的 观察致病后雌性大鼠血清及海马雌二醇(E2)和孕烯醇酮(PREG)水平的动态变化,研究海马E2水平与癫痫发作严重程度的关系. 方法 选择动情期雌性大鼠制备海人藻酸(KA)经杏仁核点燃的癫痫模型,观察大鼠癫痫发作的行为学表现.应用放射免疫法和酶联免疫吸附分析分别检测癫痫发作后0、1、2、3、4、5、6、12和24 h的大鼠以及经杏仁核注射生理盐水后相应时间的大鼠血清及海马组织E2和PREG水平.对检测结果进行统计学分析. 结果 杏仁核注入KA后5～10min大鼠均出现痫样发作,3 h达峰值,随后呈下降趋势.致痫后的大鼠血清E2水平无明显变化,但海马E2水平在癫痫发作后1 h开始上升,4 h达峰值,随后呈下降趋势,12 h恢复至对照水平,1～12 h相邻时间点E2水平差异均有统计学意义(P,0.05).此外,随着大鼠的癫痫发作程度的加重,海马E2水平逐渐升高,进行相关性检验后发现.海乌E2水平与癫痫发作严重程度呈正相关(R~2=0.646,P<0.05).致痫前及致痫后24 h内不同时间点各组大鼠海马的PREG水平没有明显变化. 结论 癫痫发作后大鼠海马E2水平的动态变化与癫痫发作程度相关.癫痫发作可以诱导大鼠海马局部E2的合成.     

红藻氨酸致痫大鼠海马S100B、CGRP蛋白表达及病理改变

目的 研究红藻氨酸(KA)致痫大鼠海马S100B、降钙素基因相关肽(CGRP)的表达及病理改变.方法 雄性SD大鼠按照完全随机数字表法分成对照组(8只)和模型组(40只),模型组再根据处死时间分为造模后6 h、12 h、24 h、72 h、1周5个亚组,每组8只.模型组采用KA建立颞叶癫痫动物模型,对照组用等体积生理盐水代替KA注射.模型组造模后6 h、12 h、24 h、72 h、1周,对照组注射后24 h取大鼠海马组织行Nissl染色、Timm染色和免疫组化染色,观察S100B、CGRP蛋白的表达情况以及海马神经元和胶质细胞的病理变化.结果 Nissl染色结果显示,模型组大鼠1周后CA3区出现大量固缩的坏死神经元,胞体萎缩,尼氏体消失.Timm染色结果显示,模型组大鼠1周后CA3区始层出现条带状分布的棕色颗粒,齿状回内分子层亦可见少量棕色颗粒.免疫组化染色结果显示,模型组大鼠海马CGRP蛋白大量表达,72 h时达到高峰,同时伴随大量神经元丧失及胶质细胞增生.结论 KA致痫大鼠出现S100B、CGRP蛋白高表达,尼氏体消失,苔藓纤维发芽等一系列病理学改变,推测S100B、CGRP蛋白参与了癫痫发生.

Abstract：

Objective To investigate the expressions of S100B and calcitonin gene related peptide (CGRP) and the pathologic alterations of the hippocampus in kainic acid (KA)-induced epileptic rats. Methods Male SD rats were randomly divided into control group (n=8) and model group (n=40).Animal models of temporal lobe epilepsy were established by intracerebroventricular injection of KA; the same volume of saline was injected into the rats in the control group. Hippocampal tissues within various phases after seizures (6, 12, 24 and 72 h, and 24 h after the success of model making) were performed Nissl staining, Timm staining and immunohistochemical staining. The expressions of S100B and CGRP were observed, and the pathologic alterations of the hippocampal neurons and glial cells were studied.Results All rat models were successfully induced with epileptic seizures. Nissl staining showed that pyknotic neuronal necrosis appeared in the CA3 area of the hippocampus in the model group with cell body atrophy and disappearance of Nissl bodies 1 week after the injection. Timm staining showed that brown particles showed stripped distribution in the CA3 area of the hippocampus and some brown particles in the molecular layer of fascia dentate. Immunohistochemical staining indicated that significant neurons lost and gliosis appeared after seizures with abundant expressions of S100B and CGRP.Conclusion KA-induced epileptic rats express abundant S100B and CGRP and appear such pathological changes as disappearance of Nissl bodies and mossy fiber sprouting, indicating that both S100B and CGRP participate in the onset of epilepsy.     

戊四氮致痫大鼠脑脊液神经元特异性烯醇化酶的水平测定

目的通过测定戊四氮致痫大鼠脑脊液中的神经元特异性烯醇化酶(NSE)水平的变化,探讨痫性发作与脑损伤之间的关系。方法110只Wistar大鼠分为实验组和对照组。实验组给予戊四氮(PIZ)腹腔注射。根据痫性发作的强度分为轻度组和重度组。用酶联免疫吸附法(ELISA)测定不同痫性发作强度、不同时间点大鼠脑脊液中NSE水平的变化,并与对照组进行对比。结果重度组脑脊液NSE水平在1h、2h、4h、6h均显著高于轻度组和对照组(P<0.01);轻度组脑脊液NSE含量在1h高于对照组(P<0.05),在2h、4h、6h显著高于轻度组;脑脊液NSE水平在痫性发作后1h迅速升高。4h达到高峰,24h恢复到正常水平。结论痫性发作可对大鼠神经细胞造成明显的损害。损害的程度与痫性发作的程度有关。痫性发作后4h可能是进行早期干预、防止脑细胞损伤的时间窗。     

癫(癇)大鼠血清、海马组织中神经元特异性烯醇化酶和S-100β蛋白的变化及其临床意义

目的 探讨红藻氨酸（KA）诱导癫痫大鼠血清及海马组织中神经元特异性烯醇化酶（NSE）和S-100β蛋白（S-100β）的变化及其临床意义。方法 180只Wistar大鼠随机分为对照组、KA组和卡马西平（CBZ）组，后两组再按癫痫发作后1h、4h、12h、24h、48h和72h不同时点分为6个亚组。以放射免疫法（RIA）和酶联免疫吸附试验（ELISA）分别测定大鼠血清和海马匀浆液中NSE和S-100β的变化。结果 癫痫发作72h内，血清和海马匀浆液中NSE和S-100β的含量是一个动态变化过程，且呈同步变化的趋势，在12h时均达到峰值。在4～48h时，KA组和CBZ组的二者含量均明显高于对照组（P〈0．05～0．01）。结论 癫痫发作后NSE和S-100β的含量升高，二者可作为癫痫发作后脑组织损伤的一个参考指标。     

海人酸致痫大鼠脑内白蛋白、S100B及GFAP动态表达的研究

目的通过测定海人酸(kainic acid,KA)致痫大鼠不同时间点脑脊液及脑组织中白蛋白、S100B蛋白及胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)表达量,探讨白蛋白、S100B蛋白和GFAP表达量变化与癫痫的关系。方法经SD大鼠侧脑室注射KA制备癫痫大鼠模型,对照组注射生理盐水。各模型组于造模后6h、24h、3d和7d四个时间点,对照组于注射生理盐水后6h,分别采用ELISA方法测定脑脊液白蛋白和S100B蛋白水平,以免疫组化法检测脑组织中白蛋白、S100B和GFAP表达,HE染色观察海马CA3区细胞及结构变化。结果 (1)脑脊液:模型组6h时白蛋白水平高于对照组(P0.05),模型组其余时间点与对照组比较差异均无统计学意义(均P0.05);其中,模型组7d、3d时白蛋白水平低于6h时(均P0.05)。模型组6h、24h、3d和7d4个时间点脑脊液S100B水平均高于对照组(均P0.05);模型组4个时间点间两两比较差异均有统计学意义(均P0.05),其中以模型组3d时最高。(2)脑组织:模型组24h及模型组6h侧脑室室管膜白蛋白表达均高于对照组(均P0.05),3d和7d时与对照组比较差异无统计学意义(P0.05);模型组四个时间点两两比较,模型组3d、7d时均低于模型组6h(P0.05),模型组7d时亦低于其他2个模型组(均P0.05)。模型组4个时间点海马区S100B表达均高于对照组(均P0.05);模型组四个时间点两两比较,模型组24h、3d和7d时均高于模型组6h时(P0.05),且模型组7d时低于模型组3d时(P0.05)。模型组3d、7d时海马区GFAP表达均高于对照组(均P0.05),其余时间点与对照组比较差异无统计学意义(P0.05);模型组四个时间点两两比较,模型组3d、7d时均高于模型组24h与6h时(均P0.05),且7d时亦高于3d时(P0.05)。(3)HE染色显示,模型组6h时海马CA3区神经元排列紊乱、分散,细胞多形性改变,部分细胞核深染;24h时细胞由圆形改变为多形性改变;3d和7d时,核深染的细胞数增加,细胞排列层次减少、紊乱,细胞坏死。结论癫痫发作后脑脊液中白蛋白、S100B及脑组织中白蛋白、S100B及GFAP表达增高。     

戊四氮诱导大鼠癫痫发作的mGLuR1α表达与神经元凋亡

目的探讨癫痫发作后mGLuR1α的表达及其与神经元凋亡的关系,并明确mGLuR1α在癫痫活动中的作用。方法将大鼠随机分为致痫后6、12、24、48、72h组及对照组,应用免疫组织化学和RT-PCR方法检测戊四氮（PTZ）诱导大鼠癫痫发作后不同时间点脑神经细胞mGLuR1α的表达变化,采用原位末端标记法和流式细胞仪检测其神经元凋亡情况。结果（1）致痫后6hTUNEL染色阳性神经元开始表达,致痫后l2h最明显,24h开始下降,48h仍有表达。致痫后12h细胞凋亡率最高,之后随时间延长逐渐下降。（2）致痫后6hmGLuR1αmRNA转录水平即达最高,12h仍处于较高水平,之后逐渐降低,72h时仍高于正常水平,而受体的蛋白表达则稍晚,于致痫后l2h达到高峰,24h开始下降。（3）致痫大鼠mGLuR1α受体表达的最早和高峰时间与TUNEL反应时间基本吻合。结论mGLuR1α表达与致痫大鼠的神经细胞凋亡机制有关,癫痫发作可导致mGLuR1α一过性高表达,从而造成神经元损伤。     

S100B蛋白与颅脑损伤预后的关系

目的研究血清和脑脊液中S100B蛋白含量与颅脑损伤预后的关系。方法用ELISA法测定125例急性颅脑损伤患者在伤后不同时间血清和脑脊液中S100B蛋白含量,结合GOS评分进行分析。结果伤后早期(24h内)血清中S100B蛋白含量均较对照组明显升高(P<0.01),在不同预后患者中S100B水平差异有显著意义(P<0.01)。脑脊液和血清中S100B变化趋势一致结论颅脑损伤后脑脊液和血清中。S100B蛋白均与患者预后密切相关,血清中S100B检测具有更大的临床应用价值。     

Genetic findings in obsessive-compulsive disorder in childhood and adolescence and in adulthood

Obsessive-compulsive disorders (OCD) are on the rise, and affected children, 1-2% of the general population, often are seriously impaired in their development. OCD is characterized by recurrent, intrusive and disturbing thoughts as well as by repetitive stereotypic behaviours. Depending on their age and developmental status, patients usually try unsuccessfully to suppress the obsessive thoughts and compulsive behaviours. The current state of genetic research on OCD and early-onset OCD is presented and discussed. OCD, especially early-onset OCD, has been shown to be familial. Convincing evidence indicates that both environmental and genetic factors substantially influence OCD. Various approaches, including linkage and association studies, yielded conflicting results as well as the notion that multiple genes of modest effect sizes, in interaction with environmental factors, cause vulnerability to the disorder. The phenotypic and genetic heterogeneity of OCD complicate the identification of specific genetic factors. Further studies have to be designed in consideration of subtypes, e.g. age at onset, symptom dimensions, or comorbid disorders.     

Changes in extra- and intracellular pH in the brain during and following ischemia in hyperglycemic and in moderately hypoglycemic rats

Incomplete forebrain ischemia of 15-min duration was induced in rats made hyperglycemic or moderately hypoglycemic prior to ischemia. Tissue CO2 tension, CO2 content, labile tissue metabolites, and extracellular pH (pHe) were measured, and intracellular pH (pHi) was derived by calculation on the assumption that cerebral intracellular fluids can be lumped into one space. In hypoglycemic animals, mean tissue lactate content increased from 2 to 10 mumol g-1. Tissue CO2 content was virtually unchanged and the CO2 tension increased from approximately 50 to approximately 145 mm Hg. In hyperglycemic animals, tissue lactate content rose to 20 mumol g-1, and the CO2 content decreased by 25%, demonstrating that some CO2 was lost to the blood supplied by the remaining perfusion. Accordingly, tissue CO2 tension did not rise above 200 mm Hg. pHe was reduced in proportion to the amount of lactate accumulated, the values obtained in hypo- and hyperglycemic animals showing relatively little scatter (6.76 +/- 0.03 and 6.25 +/- 0.04, respectively). In hypoglycemic animals the extracellular HCO-3 concentration was virtually unchanged, demonstrating that any influx of lactic acid from the cells must have been accompanied by H+ efflux and/or HCO-3 influx via independent routes. In hyperglycemic animals [HCO-3]e fell by greater than 10 mumol ml-1. In both groups [HCO-3]e was reduced during the first 5 min of recovery. Recovery of pHe was slower in hyper- than in hypoglycemic animals. During ischemia calculated pHi fell to 6.37 +/- 0.04 and 5.95 +/- 0.06 in hypo- and hyperglycemic animals, respectively. Differences in pHi were maintained for the first 15 min of recovery, but in both hypo- and hyperglycemic animals pHi had normalized after 30 min. It is concluded that preischemic hyperglycemia leads to a more pronounced intra- and extracellular acidosis than normo- and hypoglycemia, an acidosis that also resolves more slowly during recirculation.     

Dopamine-derived alkaloids in alcoholism and in Parkinson's and Huntington's diseases

Summary Tetrahydroisoquinoline (TIQ) alkaloids and 1-carboxy TIQ derivatives have been found in human fluids and/or tissues. The possible biosynthetic pathways of salsolinol (Sal), taken as an example of TIQs, are discussed, and the possibility that biosynthesis occurs through a stereospecific enzymatic reaction is considered. In this respect, it is reported that the R enantiomer of Sal predominates in urines of healthy volunteers, whereas the S enantiomer predominates in port wine and possibly in other beverages and foods, suggesting that Sal present in humans could have, at least partially, and endogenous enzymatic origin.TIQs and other dopamine-derived alkaloids are weak MAO inhibitors, the R enantiomer of Sal and salsolidine being more potent than the S form.The changes in monoamine oxidase activity and the nigrostriatal concentrations of dopamine and homovanillic acid in Parkinson's and Huntington's diseases and in alcoholism are reviewed. In these pathological situations, changes in the levels of dopamine-derived alkaloid levels may occur. The possibility that the modifications found might cause or contribute to changes in mental and/or neurophysiological states in these pathological situations is considered.