脑缺血选择性海马CA1区神经元损害的实验研究

采用Ｐｕｌｓｉｎｅｌｉ－Ｂｒｉｅｒｌｅｙ４血管阻塞脑缺血模型观察了大鼠全脑缺血２０ｍｉｎ再灌流８ｈ，ｃ－ｆｏｓ基因表达及再灌流７ｄ海马ＣＡ１区迟发性神经元损害。在缺血再灌流早期（８ｈ）海马ＣＡ１区极少ｃ－ｆｏｓ表达，而齿状回、海马ＣＡ３区、杏仁核大量ｃ－ｆｏｓ表达。缺血再灌流晚期（７ｄ）镀银染色显示海马ＣＡ１区神经元及其突触终末带呈黑色溃变相，而齿状回、海马ＣＡ３区、杏仁核呈金黄色正常相。相邻切片ＨＥ染色示缺血组海马ＣＡ１区核完整的锥体细胞数（５±２．６个／２００μｍ）与对照组（４０±２．９个／μｍ）比较差异有显著意义（Ｐ＜０．０１）。脑缺血诱导的ｃ－ｆｏｓ基因表达对于缺血易损海马ＣＡ１区迟发性神经元坏死可能起直接的调控作用。     

大鼠脑缺血再灌流后海马氨基酸水平变化与神经元损害的关系探讨

目的探讨脑缺血再灌流后海马氨基酸递质变化与神经元损害的关系。方法建立大鼠前脑缺血再灌流模型,测定海马ＣＡ１区和ＣＡ３／齿状回区游离氨基酸含量,观察阻断隔－海马通路对海马神经元损害和氨基酸水平的影响。结果（１）海马结构中仅ＣＡ１区神经元明显损害,但ＣＡ１区和ＣＡ３／齿状回区的Ｇｌｕ、Ａｓｐ和ＧＡＢＡ含量无差异。（２）阻断隔－海马通路可明显减轻海马神经元损害,但对海马氨基酸水平变化无影响。结论脑缺血再灌流后,氨基酸递质水平的异常变化不是海马ＣＡ１区神经元选择性易损的唯一决定因素,隔－海马通路末梢释放的神经递质也参与海马神经元损害过程。     

小檗碱对小鼠海马CA1区迟发性神经元坏死的影响

本文采用Ｐｕｌｓｉｎｅｌｌｉ－Ｂｒｉｅｒｌｅｙ４血管结扎致ＳＤ大鼠全脑缺血（１０ｍｉｎ）再灌流模型，分别观察了早期不同再灌流时间（１２、２４、４８ｈ）点上，大鼠海马ＣＡ１区神经元的超微结构以及早灌７ｄ时光镜结构变化，同时观察了小檗碱对ＣＡ１区迟发性神经元坏死的影响。结果显示脑缺血再灌流早期，ＣＡ１区神经元超微结构发生明显改变，７ｄ时光镜下绝大部分细胞脱失，而用药组大鼠海马ＣＡ１区神经元在相应时间点     

小檗碱对大鼠海马CA_1区迟发性神经元坏死的影响

本文采用Ｐｕｌｓｉｎｅｌｌｉ－Ｂｒｉｅｒｌｅｙ４血管结扎致ＳＤ大鼠全脑缺血（１０ｍｉｎ）再灌流模型，分别观察了早期不同再灌流时间（１２、２４、４８ｈ）点上，大鼠海马ＣＡ１区神经元的超微结构以及再灌７ｄ时光镜结构变化，同时观察了小檗碱对ＣＡ１区迟发性神经元坏死的影响。结果显示脑缺血再灌流早期，ＣＡ１区神经元超微结构发生明显改变，７ｄ时光镜下绝大部分细胞脱失；而用药组大鼠海马ＣＡ１区神经元在相应时间点上超微结构变化相对较轻，７ｄ时仍有绝大多数（８２％）细胞存活，细胞密度为１７２±１２．２个／ｍｍ，显著高于缺血对照组２７±７．６个／ｍｍ，Ｐ＜０．００１。提示小檗碱对大鼠短暂脑缺血再灌流造成的海马ＣＡ１区迟发性神经元坏死具有显著的对抗作用。     

反复性脑缺血大脑皮质LTC_4、cAMP和OFR的代谢变化

目的：研究反复脑缺血大脑皮质白三烯（ＬＴＣ４）、环腺苷酸（ｃＡＭＰ）和氧自由基（ＯＦＲ）的代谢变化与神经元损伤的关系。方法：对比观察大鼠反复性与单次性脑缺血大脑皮质ＬＴＣ４、ｃＡＭＰ、超氧化物歧化酶（ＳＯＤ）和丙二醛（ＭＤＡ）的含量变化及相应的病理改变。结果：反复缺血及再灌流早期ＬＴＣ１、ｃＡＭＰ的含量明显升高,ＳＯＤ活性显著降低,ＭＤＡ延迟性持续显著增高,皮质神经元损害显著重于单次缺血组。结论：ＬＴＣ４、ｃＡＭＰ和 ＯＦＲ均参与了反复缺血性脑损害的病理机制,可能与 Ｃａ＋＋介导的花生四烯酸（ＡＡ）瀑布效应有关。     

保精增智液对大鼠迟发性神经元坏死海马CA_1区光镜和电镜改变的影响

本研究采用Ｗｉｓｔａｒ大鼠４血管关闭法制成全脑缺血１０ｍｉｎ再灌流动物模型造成迟发性神经元坏死（ＤＮＤ），分别观察了海马ＣＡ１区再灌流后３ｄ和５ｄ的普通病理和超微结构改变，同时观察了中药保精增智液对ＤＮＤ的保护作用，结果显示再灌流３ｄ时电镜下ＣＡ１区神经元内亚细胞结构改变明显，５ｄ时光镜下出现明显的神经元脱失，造模前８ｄ给药组可明显改善再灌流３ｄ时的亚细胞结构的改变，使５ｄ时神经细胞存活数上升（１８１．６±１５．１个／ｍｍ，对照组４１．４±４．０，Ｐ＜０．０１）。该药对大鼠短暂全脑缺血再灌流造成的ＤＮＤ有保护作用。     

大鼠脑缺血再灌流后海马区一氧化氮合酶活性的变化

目的：观察鼠全脑缺血再灌流后海马区ＮＯＳ活性的变化。方法：采用大鼠４血管关闭方法制作全脑缺血再灌流模型。实验动物分为假手术组、缺血１０ｍｉｎ组、再灌注１、２、３ｄ组。测定脑缺血再灌流后海马区ＮＯＳ活性的变化。结果：全脑缺血曹澡注后海马组织ＮＯＳ活性被激活上调。结论：ＮＯ可能参与了海马ＣＡ１区迟发性神经元死亡（ＤＮＤ）的发生。     

大鼠脑缺血再灌流后海马氨基酸水平变化与神经元损害的关系 …

目的 探讨脑缺血再灌注流后海马氨基酸递质变化与神经元损害的关系。方法 建立大鼠前脑血再灌流模型，测定海马ＣＡ１区和ＣＡ３／齿太回区游离氨基酸含量，观察阻断隔－海马通路对海马神经元损害和氨基酸水平的影响。     

急性脑缺血再灌流后脑组织钙依赖中性蛋白酶的变化

本文采用大鼠全脑缺血模型,观测脑缺血再灌流脑组织Ca~(2 )依赖性中性蛋白酶(calci-um-activated neutral proteinase,calpain)活性的变化及海马C_(A1)区神经元损害改变。结果显示脑缺血再灌流脑组织calpain Ⅰ和calpain Ⅱ活性都明显升高(P<0.01),C_(A1)区神经元密度相应下降,提示calpains在脑缺血损害过程中可能起一定作用。     

轻度低温对大鼠脑缺血损伤的保护作用

本文观察了轻度低温对大鼠脑缺血的保护作用。Ｗｉｓｔａｒ大鼠在３６．８℃下将四血管阻断１０分钟，低温组３３℃低温再灌流３小时，正常体温组保持在３６．８℃，缺血后第２～６天观察动物行为，第７天处死大鼠进行脑组织病理分析。结果发现，正常体温组神经系统损害积分明显高于低温组，学习记忆能力也明显减退；正常体温组海马ＣＡ１段神经细胞损害率（９１．７％）明显高于低温组（３８．９％）。提示轻度低温对短暂脑缺血后再灌流期脑组织有明显保护作用。     

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.     

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.     

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.     

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.