胶质细胞源性神经营养因子与缺血缺氧脑损害研究进展

1993年 ,Lin等[1] 从鼠胶质细胞系B49中分离出一种能有效促进多巴胺神经元摄取多巴胺的因子 ,命名为胶质细胞源性神经营养因子 (Glialcellline derivedneurotrophicfactor ,GDNF)。自GDNF被发现以来 ,学者们对它进行了大量深入的研究 ,本文作者就近年来对GDNF的研究情况作一综述 ,并探讨其在法医学中的应用前景。1　GDNF的分子结构与基因1997年 ,Eigenbrot和Gerber报道了大鼠GDNF的晶体结构 ,与TGFβ 2十分相似 ,含有TGF β超家族的 7个保守半胱氨酸残基 ,其成熟多肽链结构中的 7个保守半胱氨酸 ,分别由 41和 10 2、 68和 13 1…     

大鼠脑损伤后GDNF表达变化的时间规律性研究

目的探讨大鼠脑损伤后胶质源性神经营养因子(GDNF)在神经元、神经胶质细胞中表达变化的时间规律性。方法以冲击应力σd为355.09kPa致大鼠脑损伤后,于不同时问段分别应用原位杂交、免疫组化、免疫组化双染色技术检测GDNF mRNA和蛋白的表达强度,用图像分析系统测定阳性反应物平均灰度,进行统计学分析。结果正常对照组GDNF mRNA和蛋白弱表达,伤后15min开始表达呈增强趋势,分别于伤后1d、2d,表达至峰值,平均灰度值分别为133.08±4.53、125.05±2.00,与对照组、邻近上组比较均具有显著性差异(P<0.05),并维持高水平表达至伤后7d,平均灰度值分别为116.65±1.31、114.20±1.68,与对照组比较具有显著性差异(P<0.05)。表达至峰值前,阳性细胞多为神经元,之后以神经胶质细胞为主。结论脑损伤后GDNF mRNA及蛋白的表达具有时间规律性,GDNF阳性细胞种类存在变化,可作为法医学推断脑损伤形成时间的指标。     

脑源性神经营养因子与脊髓损伤

脊髓损伤(SCI)后,神经轴突具有一定再生能力,但需要有神经营养因子(NTFs)的参与。脑源性神经营养因子(BDNF)作为该家族中的一员,在脊髓神经元以及胶质细胞中均可合成,不仅具有神经元保护作用,还可以促进神经细胞的分化和再生,对SCI后机体功能的恢复起重要作用。进一步研究BDNF在SCI后的作用机制及其在SCI后的含量变化是否与损伤时间、损伤程度具有相关性,有可能为SCI的治疗和法医学损伤时间的推断提供新的方法。     

脑损伤与多种神经营养因子的变化

脑损伤是法医病理学鉴定中最常见的损伤 ,对脑损伤后的病理生理改变、组织形态学改变和生化改变 ,国内外学者已进行了大量的研究工作 ,并随着免疫学、分子生物学的发展 ,对脑损伤的研究 ,已深入到分子病理水平。国内外已有学者研究报道[1] ,脑损伤后损伤部位及附近某些细胞分泌一系列促进神经细胞生长及增殖的细胞因子 ,即神经营养因子。本文就其研究进展作一综述 ,供同行们参考。1　神经营养因子概述　　神经营养因子 (ｎｅｕｒｏｔｒｏｐｈｉｃｆａｃｔｏｒｓ,ＮＴＦｓ)是一组超出普通维持生存所必须的基本营养物质以外的、对神经细胞起特…     

甲基苯丙胺致多巴胺能神经元毒性机制的研究进展

甲基苯丙胺属于苯丙胺类中枢兴奋剂,目前其滥用趋势严重。研究表明,甲基苯丙胺对动物及人类大脑纹状体多巴胺能神经元具有毒性作用。其毒性机制包括多巴胺信号转导影响和多巴胺的氧化作用、谷氨酸介导的兴奋性毒性作用、氧化应激和细胞因子的形成、线粒体功能紊乱、神经细胞凋亡、神经胶质细胞的活化以及高热等。但甲基苯丙胺对多巴胺能神经元的毒性机制并不完全清楚,本文结合文献对此进行综述,以期为相关研究提供参考。     

MA与HIV-Tat协同作用致大鼠相关脑区ROS、GSH-PX和SOD的变化

目的 观察甲基苯丙胺(MA)与HIV-Tat蛋白协同作用致大鼠相关脑区活性氧(ROS)、谷胱甘肽过氧化物酶(GSH-PX)和超氧化物歧化酶(SOD)的变化,探讨协同作用对神经系统的影响.方法 50只健康雄性SD大鼠随机分为实验组:MA组(10mg/kg MA,每日两次腹腔注射,连续4d)、HIV-Tat组(10μg HIV-Tat注入大鼠脑纹状体)和MA+HIV-Tat组(按MA组注射MA 4d后按HIV-Tat组注入HIV-Tat);对照组:生理盐水腹腔注射或纹状体内注射.各组大鼠分别于注射结束后48h和7d处死,取各脑区脑组织制作匀浆;荧光分光光度计检测ROS含量,酶标仪检测GSH-PX和SOD吸光度,再根据蛋白质的浓度分别计算其活力.结果 各实验组与对照组比较,各脑区ROS含量有不同程度增高,GSH-PX和SOD活力则有不同程度下降,差异具有统计学意义(P＜0.05);其中MA+ HIV-Tat组与MA组和HIV-Tat组比较,ROS含量升高显著,GSH-PX和SOD活力下降明显(P＜0.01).结论 MA和HIV-Tat协同作用能够产生大量的ROS,并降低GSH-PX和SOD的活力,揭示ROS、GSH-PX和SOD参与了MA与HIV-Tat的协同神经毒性作用.     

脑源性神经营养因子前体蛋白研究进展

脑源性神经营养因子前体蛋白（pro-BDNF）是成熟型脑源性神经营养因子（mBDNF）的前体形式。最新研究表明，pro-BDNF不仅作为mBDNF的前体形式存在，还可由神经细胞分泌到胞外，发挥与mBDNF不同的生物学效应。本文综述了pro-BDNF蛋白的分子结构、在中枢神经系统的分布、受体、生理效应、分泌与调节以及pro-BDNF与长时程抑制、突触可塑性、记忆形成及毒品成瘾的相关性等方面的研究进展。     

不同时程吗啡依赖对大鼠中脑黑质多巴胺神经细胞的影响

目的观察不同时程吗啡依赖对大鼠中脑黑质(Substantia nigra,SN)多巴胺能神经细胞的影响。方法按逐日递增原则背部皮下注射盐酸吗啡,建立吗啡依赖大鼠模型,取脑组织经10%福尔马林液固定后石蜡包埋,组织连续切片,免疫组织化学和免疫荧光染色,观察多巴胺能神经细胞特异性标记物酪氨酸羟化酶(tyrosine hydroxylase,TH)蛋白表达变化;Fluoro-Jade B染色观察吗啡依赖不同时程黑质多巴胺能神经细胞变性坏死情况。结果 TH免疫组化结果显示随着吗啡依赖时间的延长黑质阳性细胞逐渐减少,吗啡依赖6周组阳性细胞减少明显。Fluoro-Jade B染色结果证实多巴胺能神经细胞发生了变性坏死。结论较长时程吗啡依赖大鼠黑质多巴胺能神经细胞损伤明显。     

甲基苯丙胺染毒动物模型的建立与评价

苯丙胺类中枢兴奋剂是21世纪最广泛滥用的毒品.甲基苯丙胺(methamphetamine,MA)的中毒机理、精神依赖性、耐药性以及治疗药物的研发是当前研究的热点.MA中毒动物模型的建立是研究MA相关问题的基础.MA动物模型建立的规范化和标准化对以后MA的进一步研究奠定了实验基础.本文结合国内外关于MA中毒动物的文献资料,通过对MA急性、亚急性以及慢性中毒动物模型研究的论述.对造模原理、造模方法 和评价标准进行了探讨,并指出建立以动物为主体的MA中毒模型来进行相关实验研究的必要性以及重要性.     

甲基苯丙胺心肌毒性的研究进展

甲基苯丙胺(MA)是近年来在我国公共场所流行滥用的成瘾性药物,俗称"冰毒"。目前实验研究发现,MA对人体多个系统都具有毒性作用,其中对心血管系统的毒性损害作用较为显著。临床表现上,MA中毒主要导致了以心率和血压改变为特异性表现的一系列症状,以及继发的心脏结构改变所导致的心脏损害;病理学上,MA中毒导致了心肌坏死、心肌间质炎细胞增多、心肌纤维化、心肌梗死等。法医学研究中,发现了MA急性中毒导致死亡的主要原因是MA引起的心律失常和室颤,慢性中毒的死因较多,以MA慢性中毒导致高血压、心肌病、心肌梗死等为主。MA中毒的心肌毒性的分子机制表现为心肌内多种蛋白质表达的改变。目前MA心肌毒性的机制研究较多,但仍未完全查明。本文通过对近年来MA心肌毒性研究现状进行综述,为后续研究提供参考。     

重度颅脑损伤后GDNF表达的实验研究

目的观察重度颅脑损伤后GDNF的表达变化规律。 方法应用免疫组织化学方法和图像分析技术,对大鼠重度颅脑损伤后不同时间大脑皮层、丘脑和脑干等几个脑区内GDNF的表达变化进行研究。结果CDNF在脑损伤后1d表达开始增高,3d达表达最高峰,5d时回落不明显,7d有所回落,但仍高于正常水平。结论GDNF在脑损伤后的时序性变化规律使其有可能成为一种脑损伤时间推断的客观指标。     

多巴胺受体基因遗传多态性与精神分裂症的关联及法医学意义

精神分裂症是一种常见的多因子参与的复杂疾病,司法精神病学鉴定中对精神分裂症的涉及甚多,但无有效的生物学鉴定指标。研究表明,多巴胺神经递质功能紊乱可能在精神分裂症的发生及其主要症状中发挥重要作用。本文综述了多巴胺受体的分类、基因结构以及近年来关于多巴胺受体基因遗传多态性与精神分裂症的关联研究及其法医学意义。     

Morphological signs of ethanol poisoning, alcohol abstinence and chronic alcoholic intoxication in the mesocorticolimbic dopaminergic system

Forensic medical diagnostics of ethanol poisoning, alcohol abstinence, and chronic alcoholic intoxication of the mesocorticolimbic dopaminergic system remains an unresolved problem and encounters difficulties. This situation is due not only to the marked vulnerability of the neurons of the dopaminergic system but also to the fact that its mechanisms are poorly understood. The objective of the present work was to substantiate and develop diagnostic criteria for ethanol poisoning, alcohol abstinence, and chronic alcoholic intoxication of the neurons both in the mesocorticolimbic dopaminergic system and in other brain regions. The object of the study was the brain of healthy adult subjects who died from alcohol intoxication (in the period of ethanol resorption) and under conditions of alcohol abstinence (completion of the abstinence course). The purpose of the study was to elucidate factors responsible for the different degree of damage to the neurons of various identification groups (intact, hypochromic, picnomorphic, shadow) and macrogliocytes. The cells of all these types were counted at an area of 0.25 sq. mm within 4 squares each having a side of 250 mcm in length. The absolute and relative number of neurons in each group as well as the number of polyneuronal satellite cells per one intact neuron was determined. It was shown that alcohol intoxication is associated with acute swelling of and severe damage to brain neurons caused by the combination of such factors as toxic effect of ethanol, excessive production of catecholamines, and functional overstrain of dopaminergic neurons. The severity of acute alcohol damage to the neurons decreased with the distance from the mid-brain dopaminergic nuclei. Restoration of neurons during alcohol abstinence was due to compensatory activation of interactions between neurons and glial cells. It decreased in the sequence from the paranigral nucleus of the ventral portion of mesencephalic tegumentum to the medial portion of the accumbence nucleus (field 24b, layer III of field la, layer V of field 1) depending on the initial severity of acute damage in the brain region being examined. The severity of damage to the neurons of the mesocorticolimbic dopaminergic system under conditions of chronic alcohol intoxication estimated from the number of shadow neurons was similar to the degree of acute swelling associated with ethanol poisoning and decreases from a maximum in the nuclei of the mesocorticolimbic dopaminergic system to a minimum in layer III of field 1.     

The Contingent Effects of Fatherhood on Offending

A growing body of research assesses the relationship between fatherhood and desistance. Qualitative studies typically find fatherhood reduces offending, especially substance use; yet, quantitative studies have produced mixed findings. Guided by life-course theory, this study hypothesizes that fatherhood affects certain kinds of offending and fatherhood’s effects on offending are most pronounced among fathers who reside with their child. To test our hypotheses, NLSY97 data are employed along with fixed-effects regression analyses to estimate the relationship between fatherhood and offending, while controlling for time-varying and time-stable competing factors. Periods of fatherhood are associated with reductions in licit and illicit substance use but not other kinds of offending, and these effects are considerably stronger in periods in which fathers resided in the same household as their child. By contrast, residential fatherhood is associated with reductions in property offending and arrest. These results confirm the findings of qualitative research in that fatherhood, particularly residential fatherhood, reduces substance use but has weaker effects on other kinds of deviance.     

Some thoughts on the neurobiology of stalking

The authors examine the crime of stalking, including the cognitive traits, emotional reactions, attachment pathology, violence patterns and sex differences of samples of stalking offenders. They focus on two common types of stalkers: 1) those who sustain pursuit of a former sexual intimate who has rejected them; and 2) those who pursue a stranger or acquaintance who has failed to return the stalker's romantic overtures. The authors discuss data from neuroimaging (fMRI) studies of romantic love which suggest that these forms of stalking may be associated with heightened activity of subcortical dopaminergic pathways of the "Reward System" of the brain, perhaps in combination with low activity of central serotonin. The authors propose that this set of neural correlates may contribute to the stalker's focused attention, increased energy, following behaviors, obsessive thinking about and impulsivity directed toward the victim. To further explore the neural systems associated with stalking behavior, they also discuss several biopsychological phenomena associated with romantic rejection, including the "protest response," "frustration attraction," "abandonment rage" and "mate guarding." They illustrate the parallels between stalking and addiction. They conclude that stalking may be associated with a specific set of biological components and they offer suggestions for further research into this pathological emotional/motivational state.     

Differential Effects of Adult Court Transfer on Juvenile Offender Recidivism

Prior research indicates that adolescent offenders transferred to adult court are more likely to recidivate than those retained in the juvenile system. The studies supporting this conclusion, however, are limited in addressing the issue of heterogeneity among transferred adolescents. This study estimates the effect of transfer on later crime using a sample of 654 serious juvenile offenders, 29% of whom were transferred. We use propensity score matching to reduce potential selection bias, and we partition the sample on legal characteristics to examine subgroup effects. We find an overall null effect of transfer on re-arrest, but evidence of differential effects of transfer for adolescents with different offending histories. These results suggest that evaluating the effects of transfer for all transferred adolescents together may lead to misguided policy conclusions.     

The impact of situational factors, officer characteristics, and neighborhood context on police behavior: A multilevel analysis

While a considerable number of studies had been conducted to examine the effects of various variables on police behavior, very few studies had simultaneously analyzed factors that accounted both for police coercive and noncoercive behaviors. Equally limited is the research on the influences of officer characteristics and neighborhood context on police behavior controlling for all individual situational factors. Using observational and survey data collected by a large-scale project and hierarchical linear modeling techniques, this study assessed the effects of situational, officer, and neighborhood variables on police coercive and noncoercive actions, as well as the cross-level effects between these variables. Findings showed that situational characteristics played a strong role in determining officer coercive behavior, but not noncoercive activities. Similarly, officer-level predictors explained better officers' variation in coercive behavior than noncoercive behavior. Meanwhile, socially disadvantaged neighborhoods were more prone to receive coercive activities than were other neighborhoods. Implications for policy and future research are discussed.     

Research design influence on study outcomes in crime and justice: a partial replication with public area surveillance

Does the quality of research design have an influence on study outcomes in crime and justice? This was the subject of an important study by Weisburd et al. (2001). They found a moderate and significant inverse relationship between research design and study outcomes: weaker designs, as indicated by internal validity, produced stronger effect sizes. Using a database of evaluations (n?=?136) from systematic reviews that investigated the effects of public area surveillance on crime, this paper carried out a partial replication of Weisburd et al.??s study. We view it as a partial replication because it included only area- or place-based studies (i.e., there were no individual-level studies) and these studies used designs at the lower end of the evaluation hierarchy (i.e., not one of the studies used a randomized experimental design). In the present study, we report findings that are highly concordant with the earlier study. The overall correlation between research design and study outcomes is moderate but negative and significant (Tau-b?= ?C.175, p?=?.029). This suggests that stronger research designs are less likely to report desirable effects or, conversely, weaker research designs may be biased upward. We explore possible explanations for this finding. Implications for policy and research are discussed.