12周人胚额叶大脑皮质神经元核仁的超微结构

本文通过透射电镜观察,从超微结构的角度对12wk人胚额叶大脑皮质神经元的核仁作了形态与功能方面的初步探讨,结果表明该时期的大脑皮质神经元处于分化发育较活跃时期。     

胎儿额叶大脑皮质在发育过程中神经细胞数密度变化的形态计量分析

本文以7个月龄的12例胎儿额大皮质为研究对象、通过对大脑皮质各层神经细胞数度测量,从形态计量角度探讨了人胎儿额叶大脑皮质发育规律。结果表明,胎儿额叶大脑皮质各层神经细胞数密度于24—28周龄呈局部时相上升:28～43周呈下降期;24～43周呈下降总趋势。     

大鼠染铝对脑神经细胞超微结构的影响

目的：研究亚慢性染铝对断乳大鼠海马神经元和神经突触的超微结构的影响,以明确铝对发育中的中枢神经系统中海马组织的毒性作用。方法予各剂量组大鼠染铝90 d,处死后取海马组织,经处理后固定切片,采用透射电镜技术观察大鼠海马组织神经元和神经突触超微结构。结果随着染铝剂量的增加,大鼠海马神经元和神经突触的超微结构损害程度随之增加。结论染铝可以损害大鼠海马神经元和神经突触的超微结构。     

文冠果壳苷对大鼠大脑中动脉缺血再灌注损伤的改善作用及机制初探

目的考察文冠果壳苷对大鼠大脑中动脉缺血再灌注损伤的改善作用,并从改善突触功能的角度,探讨其作用机制。方法利用大脑中动脉阻塞法(MCAO)制备大鼠局灶性脑缺血再灌注损伤模型,TTC染色法计算脑梗死面积,HE染色法观察海马CA1区神经细胞病理形态改变,透射电镜观察大脑皮层缺血半暗带区神经元及突触超微结构改变,Western blotting检测突触相关蛋白SYP、PSD95及GAP43的表达。结果文冠果壳苷显著改善模型大鼠神经功能缺失症状,减少脑梗死面积,改善海马CA1区神经细胞的病理改变,并改善脑缺血半暗带区神经元及突触超微结构的损伤,增加突触相关蛋白SYP、PSD95及GAP43的表达。结论文冠果壳苷可显著改善大鼠大脑中动脉缺血再灌注损伤,其机制可能与促进突触重塑和/或减轻突触结构与功能的损伤有关。     

汽车尾气对大鼠皮层神经细胞的影响

<正>随着机动车数量增多,汽车尾气对健康构成了巨大的威胁。汽车尾气中存在的多种化学物质不仅可作用于鼻腔、咽喉、气管等呼吸道部位,有研究显示汽车尾气还具有神经毒性,能导致脑组织中多巴胺神经元的数目减少[1]。汽车尾气对胎儿神经系统的发育是否有影响未见报道。本研究以新生的Wistar大鼠和每天吸汽车尾气的大鼠所生的新生Wistar大鼠为观察对象,进行离体神经细胞培养,观察大鼠神经细胞存活的天数、Calcein-AM染色结果、神经细胞活力测定等。报告如下。     

医学本科生神经生物学实验课的设计实施

神经生物学是从分子,细胞和整体水平研究神经系统的结构,功能与发育等问题的综合性科学。本课程旨在探讨最基础也是最前沿的知识．是联系基础学科与临床学科的桥梁,主要研究与临床医学密切相关的神经系统的组成与结构.神经递质.神经调质以及神经元信号传递,临床重大神经系统疾病的致病机理等,为学习临床医学课程.在形态结构,分子水平上认识神经系统疾病的病因和发病机理、准确诊断和防止疾病方面奠定扎实的基础。是学习基础医学、临床医学和军事医学课程的必备课程。神经生物学的学习过程也是理论与实践并重的过程。     

神经干细胞研究的几个问题

神经干细胞的发现是神经科学研究的里程碑，改变了成熟神经系统不会出现新生神经元的认识。神经干细胞生长分化特性的研究使人们对神经细胞生长、发育及可塑性的认识更加深入，也为一些神经疾病的治疗带来了希望。1神经干细胞概念和特性神经干细胞是指具有分化为神经元、星形胶     

外泌体在脑缺血再灌注损伤中的作用研究进展

脑缺血再灌注（I/R）损伤发病机制复杂,与炎症反应、神经元凋亡等因素相关。外泌体因可改善神经通讯发生、促进神经元以及髓鞘突触的发育、重构神经血管单元和保持神经系统的稳态,成为治疗脑I/R损伤的研究热点。不同来源的外泌体在脑I/R中发挥不同作用,急性脑梗死患者来源的外泌体可导致脑损伤加重,而正常干细胞或神经系统细胞来源的外泌体能在损伤发生后阻止相关神经细胞凋亡和改善炎症反应等。本文简述外泌体在脑I/R损伤中的作用,并以不同细胞来源（包括干细胞、神经系统细胞和其他组织细胞）的外泌体进行分类,对外泌体在脑I/R损伤中的神经生物学机制以及可能的治疗手段等的研究进展进行综述,以期为该类新药研发提供依据。     

儿童血铅与神经元特异性烯酵化酶的关系

铅对儿童神经系统的损伤主要影响儿童的智能和行为发育。血铅水平每上升0．483μmol／L，儿童的智商要降低6～8分。神经元特异性烯醇化酶（NSE）特异性地存在于神经元和神经内分泌细胞中，能从损伤的神经元内溢出，通过血脑屏障进入体循环，因而外周血中检测到NSE浓度的升高提示有神经细胞的破坏，神经系统已产生亚临床的损伤。随着脑损伤的恢复，NSE的浓度却逐渐下降，是反映神经元损伤的较为敏感的特异性指标，本实验通过测定不同血铅水平的儿童的血清NSE来探讨铅对儿童神经系统的损害。     

胎儿额叶大脑皮质在发育过程中厚度变化的形态计量研究

本文以8个胎龄组的13例胎儿额叶大脑皮质为研究对象,通过对大脑皮质各层厚度及总厚度的测量,从形态计量的角度探讨人胎儿额叶大脑皮质发育规律。结果表明,随着所取胎龄组胎龄的逐渐增大,胎儿额叶大脑皮质各层厚度及总厚度均呈逐渐增大的趋势。     

Use of high content image analysis to detect chemical-induced changes in synaptogenesis in vitro

Synaptogenesis is a critical process in nervous system development whereby neurons establish specialized contact sites which facilitate neurotransmission. Early life exposure to chemicals can result in persistent deficits in nervous system function at later life stages. These effects are often the result of abnormal development of synapses. Given the large number of chemicals in commerce with unknown potential to result in developmental neurotoxicity (DNT), the need exists for assays that can efficiently characterize and quantify chemical effects on brain development including synaptogenesis. The present study describes the application of automated high content image analysis (HCA) technology for examining synapse formation in rodent primary mixed cortical cultures. During the first 15 days in vitro (DIV) cortical neurons developed a network of polarized neurites (i.e., axons and dendrites) and expression of the pre-synaptic protein synapsin increased over time. The localization of punctate synapsin protein in close apposition to dendrites also increased, indicating an increase in synapse formation. Results demonstrated that: (1) punctate synapsin protein with a spatial orientation consistent with synaptic contact sites could be selectively measured, (2) the critical period for synaptogenesis in cortical cultures was consistent with previous reports, (3) chemicals known to inhibit synapse formation decreased automated measurements of synapse number and (4) parallel evaluation of neuron density, dendrite length and synapse number could distinguish frank cytotoxicity from specific effects on synapse formation or neuronal morphology. Collectively, these data demonstrate that automated image analysis can be used to efficiently assess synapse formation in primary cultures and that the resultant data is comparable to results obtained using lower throughput methods.     

果糖二磷酸锌对体外培养新生小鼠大脑皮层神经细胞生长发育的影响

目的 :研究不同剂量果糖二磷酸锌 (ZnFDP)对体外培养新生小鼠大脑皮层神经细胞的生长发育的影响。方法 :采用体外培养的新生小鼠大脑皮层神经细胞 ,在血清培养液中加入低、中、高3种剂量ZnFDP ,使之终浓度分别为2 5、12 5、125μg/ml,通过细胞形态学观察、神经元突起和胞体生长状况的定量比较、不同培养期细胞存活数和培养液中乳酸脱氢酶 (LDH)渗漏量的测定来考察ZnFDP对大脑皮层神经细胞生长发育的影响。结果 :培养48h后与对照组比较 ,中剂量ZnFDP组大脑皮层神经元的突起数目增多 ,突起长度增加 ,胞体长径没有显著性变化 ;低剂量ZnFDP组与对照组比较 ,各项指标没有显著性差别 ;高剂量ZnFDP组则明显抑制神经细胞分化。培养3、7、10d ,中剂量ZnFDP组细胞存活数明显高于对照组 ;培养7、10d ,中剂量ZnFDP组LDH渗漏量明显低于对照组。结论 :适量的ZnFDP能促进大脑皮层神经细胞的生长发育。     

Electrophysiological changes at a central noradrenergic synapse during thallium toxicosis

The actions of chronically administered thallous acetate were studied electrophysiologically at a central noradrenergic synapse. Administration of thallous acetate (4 mg/kg for 7 days) to rats produced a significant increase in the spontaneous discharge rate of cerebellar Purkinje neurons. Experiments with various pharmacologic agents were performed to determine if this increase in spontaneous rate was due to interference with the noradrenergic innervation of the Purkinje neurons. Rats treated with thallous acetate were resistant to parenterally administered amphetamine and haloperidol; these agents decrease and increase, respectively, the spontaneous Purkinje neuron discharge in control (sodium acetate-treated) rats. 6-Hydroxydopamine (6-OHDA) administered intracisternally to sodium acetate-treated rats produced a pronounced increase in spontaneous Purkinje cell discharge, whereas this catecholaminergic-specific neurotoxin did not alter the basal discharge rate of thallous acetate-treated animals. Locus coeruleus stimulation produced potent inhibitions of Purkinje neuron discharge in sodium acetate-treated animals, but such stimulation was without effect on Purkinje cells from thallous acetate-treated animals. Taken together, these data suggest that thallium intoxication causes a reduction in catecholaminergic input into central neurons. Such changes may contribute to the neurological sequelae of thallium toxicosis.     

咖啡酸对全脑缺血再灌注模型大鼠脑损伤的保护作用研究

目的:探讨咖啡酸对全脑缺血再灌注模型大鼠脑损伤的保护作用及其机制。方法:将大鼠随机分为假手术组(生理盐水)、模型组(生理盐水)和咖啡酸低、中、高剂量组(咖啡酸溶液,10、30、50mg·kg-1),每组7只,分别腹腔注射相应药物后建立全脑缺血再灌注模型,以寻台潜伏期为指标,用Morris水迷宫检测大鼠空间学习记忆能力,其后,采用苏木精-伊红染色法观察各组大鼠海马组织病理学变化和固定视野内神经元细胞计数,并考察海马组织中超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量及核转录因子NF-κBp65阳性细胞的表达。结果:与模型组比较,咖啡酸低、中、高剂量组大鼠5d内的寻台潜伏期明显缩短(P<0.05或P<0.01),海马CA1区神经元损伤程度降低、神经元细胞数目明显增加(P<0.05或P<0.01),海马组织中SOD活性明显增加、MDA含量和NF-κBp65阳性细胞表达明显降低(P<0.05或P<0.01)。结论:咖啡酸可能通过降低NF-κBp65阳性细胞表达,抑制中枢神经系统炎症反应和氧化应激来实现对全脑缺血再灌注模型大鼠脑损伤的保护作用。     

Neuroprotective effects of a standardized extract of Diospyros kaki leaves on MCAO transient focal cerebral ischemic rats and cultured neurons injured by glutamate or hypoxia

Naoxinqing (NXQ, a standardized extract of Diospyros kaki leaves) is a patented and approved drug of Traditional Chinese Medicine (TCM) used for the treatment of apoplexy syndrome for years in China, but its underlying mechanism remains to be further elucidated. The present study investigates the effects of NXQ against focal ischemia/reperfusion injury induced by middle cerebral artery occlusion (MCAO) in rats and against glutamate-induced cell injury of hippocampal neurons as well as against hypoxia injury of cortical neurons. Oral administrations of NXQ at 20, 40, 80 mg/kg/day for 7 days (3 days before MCAO and 4 days after MCAO) significantly reduced the lesion of the insulted brain hemisphere and improved the neurological behavior of the rats. In primary rat hippocampal neuron cultures, treatment with NXQ at 5 - 20 microg mL concentration protects the neurons against glutamate-induced excitotoxic death in a dose-dependent manner. In primary rat cerebral cortical neuron cultures, pretreatment with 5 - 100 microg/mL NXQ also attenuates hypoxia-reoxygen induced neuron death and apoptosis in a dose-dependent manner. These results suggest that NXQ significantly protects the rats from MCAO ischemic injury in vivo and the hippocampal neurons from glutamate-induced excitotoxic injury as well as cortical neurons from hypoxia injury in vitro by synergistic mechanisms involving its antioxidative effects. NXQ:Naoxinqing CNS:central nervous system MCAO:middle cerebral artery occlusion I/R:ischemia and reperfusion.     

3,4-Methylenedioxy-N-methamphetamine (ecstasy) promotes the survival of fetal dopamine neurons in culture

The current study examined whether modest concentrations of MDMA could increase the survival and/or neurite outgrowth of fetal midbrain dopamine (DA) neurons in vitro since increased DA neurite outgrowth has been previously observed in vivo from prenatal exposure. MDMA concentrations in fetal brain were quantified to determine relevant in vivo concentrations to employ in vitro. A dose response study in vitro demonstrated that MDMA, at concentrations observed in vivo, resulted in increased, DA-specific, neuron survival. Higher doses resulted in non-specific neurotoxicity. MDMA application immediately after culture establishment resulted in greater survival than delayed application, however both were superior to control. MDMA significantly increased the expression of the slc6a3 gene (dopamine transporter; DAT) in culture. Co-application of the DAT reuptake inhibitor methylphenidate (MPH) with MDMA attenuated this effect. Progressive reductions in MPH concentrations restored the MDMA-induced survival effect. This suggests that MDMA's action at DAT mediates the survival effect. Neurite density per neuron was unaffected by MDMA in vitro suggesting that MDMA promotes DA neuron survival but not neurite outgrowth in culture. Finally, animals prenatally exposed to MDMA and examined on postnatal day 35 showed an increase in tyrosine hydroxylase-positive (TH+) neurons in the substantia nigra but not in the ventral tegmental area. These data suggest that during development, MDMA can increase the survival of DA neurons through its action at its transporter. Understanding how MDMA increases DA neuron survival may provide insight into normal DA neuron loss during development.     

抗脑衰胶囊对Aβ25-35诱导的神经元损伤作用的影响

目的探讨抗脑衰胶囊对Aβ25-35诱导的皮质神经元损伤作用的影响。方法采用Aβ25-35（10μmol/L）处理原代培养的大鼠皮质神经元损伤模型,加入抗脑衰胶囊含药血清共培养24h,倒置显微镜下观察神经元的形态变化,应用MTT法测定神经元存活率。结果与模型组相比,抗脑衰胶囊含药血清共培养组神经元的生存状态明显改善,神经元存活率明显提高。结论抗脑衰胶囊可显著对抗Aβ25-35对神经元的神经毒性作用,提高细胞存活率。     

参附注射液对局灶性脑缺血再灌注损伤大鼠中枢神经系统病理学的影响

目的:研究参附注射液(SFI)对局灶性脑缺血再灌注损伤大鼠中枢神经系统病理学的影响。方法:80只雄性大鼠均分为4组,即空白对照、假手术、模型和SFI组。大鼠麻醉5min后经尾iv参附注射液10mg·kg-1,复制右侧大脑中动脉缺血2h再灌注24h模型。比较各组血脑屏障和大脑皮质神经元的病理改变以及相应功能的变化。结果:电镜下模型组大脑皮质毛细血管周围水肿及管腔受压严重,神经元肿大,细胞膜连续性中断,胞浆肿胀、空泡化,细胞核肿胀、破裂,核基质密度增加,异染色质增加。SFI组大脑皮质毛细血管周围水肿和毛细血管管腔受压程度明显轻于模型组,神经元肿胀,细胞膜边界欠清楚,胞浆肿胀,细胞核肿胀,核膜尚完整,核基质密度轻度增加,异染色质轻度增加。与模型组比较,SFI组缺血2h神经功能缺损评分无显著性改变;SFI组再灌注24h后神经功能缺损评分显著降低(P<0.01)。结论:SFI可减轻局灶性脑缺血再灌注损伤大鼠中枢神经系统病理学改变程度,进而减轻神经功能受损伤的程度。     

星形胶质细胞在脑缺血中的变化和作用

星形胶质细胞作为中枢神经系统数量最多的细胞,它在脑缺血中发生增殖、肥大,特异性标记物胶原纤维酸性蛋白和波形蛋白表达明显增加。星形胶质细胞在缺血状态下具有较强的耐受力,可通过多种途径保护神经元。并且它也通过产生兴奋性氨基酸、炎症介质,降低缝隙连接等损伤神经元。因此,星形胶质细胞在脑缺血中起着损伤和保护脑组织的双重作用。明确星形胶质细胞在脑缺血中的作用及其机制,可能将为脑缺血的治疗提供新的靶点。