多发性硬化的发病机制

多发性硬化是一种慢性的中枢神经系统炎性疾病,表现为中枢神经系统神经元的脱髓鞘。病程进展中出现少突神经胶质细胞损害和轴索破坏。尽管多发性硬化病因不清,目前已知自身免疫和感染是发病的重要因素,也有遗传因素参与其中。本文强调了B细胞的影响和膜脂肪代谢也是多发性硬化发病机制的重要因素,尤其与患者血浆、红细胞和白细胞、脑脊液中亚麻酸(C18:2n-6)和花生四烯酸(C20:2n-6)水平减少相关。     

尿酸与多发性硬化

近年来有关研究发现,多发性硬化病人的血清尿酸水平显著低于对照,且可能与疾病的活动性、病程、神经伤残程度及性别有关。尿酸被成功地用于治疗多发性硬化的动物模型,多发性硬化病人口服尿酸前体肌苷可以使临床症状改善,提示对尿酸与多发性硬化的关系研究,有望为进一步探索多发性硬化发病机理及更合理的治疗方案找到新的突破点。     

多发性硬化和尿酸

多发性硬化(multiple sclerosis，MS)是自身免疫反应所致的中枢神经脱髓鞘性疾病，病变晚期轴索亦可受到破坏。过氧化物是其病理机制中一个重要因素。自从在多发性硬化发病机制的研究中发现内源性过氧化物清除剂尿酸对多发性硬化有抑制作用后，该机制得到深入研究，并发现尿酸是反映多发性硬化病情活动性的重要指标。采用尿酸前体治疗多发性硬化也取得了重要进展。     

多发性硬化NAWM微观病变的研究

近年来研究发现多发性硬化患者正常表现白质(NAWM)区域存在微观病变,有明确的病理学改变和复杂的病理生理学变化,运用磁共振波谱等影像学技术有助于发现NAWM微观病变。此类病变与硬化斑之间相互影响,并能反映多发性硬化临床症状严重程度和病情进展。     

多发性硬化与缺血性脑血管病关系的研究进展

近来研究发现多发性硬化与缺血性脑血管病之间存在密切联系:多发性硬化患者较正常人更易患缺血性心脑血管病;多发性硬化患者存在缺氧诱导因子、脂蛋白相关的磷脂酶A2等缺血性损害标记物表达的增高;多发性硬化患者存在广泛的与缺血性脑血管病类似的大脑低灌注。多发性硬化本身存在的病理生理机制包括自身免疫炎症反应、氧化应激过程、高同型半胱氨酸血症等引发的血管内皮功能损害,可能是造成缺血性脑血管病的原因。多发性硬化与缺血性脑血管病之间的联系的研究有助于阐明其发病机制并提供新的治疗方法。     

2010年修订版多发性硬化诊断标准解读

介绍了多发性硬化诊断国际专家小组对多发性硬化临床诊断标准的最新修订。基于近年来在影像及实验室等相关领域关于多发性硬化诊断的最新研究结果及专家意见,重点在阐述时空多发性的客观证据以及原发进展型多发性硬化的诊断方面进行了修订,在保持敏感性和特异性的基础上一定程度简化了多发性硬化的诊断过程。该修订标准有可能应用于儿童、亚洲人群及拉丁美洲人群,但存在局限性。     

细胞因子与多发性硬化

多发性硬化是与免疫有关的疾病,近年来研究表明细胞因子在多发性硬化发病过程中起作用。本文对细胞因子与多发性硬化的关系做一综合性阐述。     

多发性硬化20例临床分析

目的 :探讨多发性硬化的临床症状及MRI对其诊断的价值和意义。方法 :综合分析 2 0例多发性硬化患者一般资料、MRI、脑脊液检查及治疗转归。结果 :多发性硬化好发于 10～ 4 0岁 ,女性多见 ,起病形式及临床症状多样 ,病程呈复发与缓解 ,MRI对多发性硬化病灶的发现率可达 10 0 %。糖皮质激素治疗有效 ,但随着病程的延长 ,复发次数的增多 ,激素治疗欠佳。结论 :根据临床特点、影像学检查、脑脊液及神经电生理检查可提高多发性硬化的确诊率     

Th17细胞在多发性硬化发病过程中的作用

多发性硬化被认为是Th1细胞介导的自身免疫病。近年来,一种以分泌IL-17为特征的Th17细胞被发现与自身免疫反应有关。越来越多的证据表明,Th17细胞参与自身免疫性炎症的病理过程,在实验性自身免疫性脑脊髓炎和多发性硬化的发生发展过程中发挥着重要作用。其介导多发性硬化的具体机制仍不清楚,可能与破坏血脑屏障、诱导单核细胞扩增并分化为髓样树突状细胞以及促进炎性细胞因子网络的形成等有关。本文综述了关于Th17细胞的发现、分化以及在多发性硬化发病机制中的作用。     

多发性硬化的轴索损伤及其机制

19世纪初即有文献提及多发性硬化(MS)的轴索病变[1].Charcot和Marburg都描述了多发性硬化的病理改变:脱髓鞘、反应性神经胶质增生和轴索相对保留.1936年,Putnam报告多发性硬化病灶轴索缺失达50%;而Greenfield则认为,90%的多发性硬化病灶轴索密度正常,并指出该项研究结果与前人的差异归功于高敏感性的轴索染色方法.然而,在随后的研究中,轴索病变在多发性硬化发病机制中的作用并未引起足够重视.     

Characteristics of the sympathetic innervation of the nictitating membrane and of the vasculature of the nose and tongue of the cat

Summary Vasomotor responses from the nasal mucosa and tongue, and contractions of the nictitating membrane, were recorded on stimulation of the cervical sympathetic or internal carotid nerves.Preganglionic sympathetic nerve fibres which elicited a membrane response possessed a lower threshold than those which evoked nasal vasoconstriction, while the latter displayed a lower threshold than fibres which evoked tongue vasoconstriction. The sympathetic vasodilator fibres to the tongue, whose activity was revealed after-receptor blockade, had a similar threshold to the vasoconstrictor fibres.Membrane contraction, nasal vasoconstriction and occasionally tongue vasoconstriction could be evoked by stimulating the internal carotid nerve. The postganglionic fibres innervating the nasal mucosa had a similar threshold to those of the nictitating membrane, which may indicate that there are small myelinated fibres innervating the mucosa.The preganglionic compound nerve action potential had four major components, S₁–S₄. S₁, S₂ and usually S₃ fibres were associated with membrane contraction; S₂, S₃ and sometimes S₁ fibres were associated with nasal vasoconstriction; and S₃, usually S₂ and occasionally S₁ fibres were associated with vasoconstriction in the tongue. It is concluded that each of these three groups of nerve fibres, but not S₄ fibres, may include fibres associated functionally with the three effectors.There was a considerable difference between the relative amplitude of the responses of the three effectors elicited by stimulation of the cervical sympathetic nerve at frequencies between 0.2 and 2 Hz. Vasoconstrictor responses were relatively larger than membrane contractions suggesting differences in the mechanisms of neurotransmission at the neuroeffector junctions.     

Development of the projection from the nucleus of the brachium of the inferior colliculus to the superior colliculus in the ferret

Neurons in the deeper layers of the superior colliculus (SC) have spatially tuned receptive fields that are arranged to form a map of auditory space. The spatial tuning of these neurons emerges gradually in an experience-dependent manner after the onset of hearing, but the relative contributions of peripheral and central factors in this process of maturation are unknown. We have studied the postnatal development of the projection to the ferret SC from the nucleus of the brachium of the inferior colliculus (nBIC), its main source of auditory input, to determine whether the emergence of auditory map topography can be attributed to anatomical rewiring of this projection. The pattern of retrograde labeling produced by injections of fluorescent microspheres in the SC on postnatal day (P) 0 and just after the age of hearing onset (P29), showed that the nBIC-SC projection is topographically organized in the rostrocaudal axis, along which sound azimuth is represented, from birth. Injections of biotinylated dextran amine-fluorescein into the nBIC at different ages (P30, 60, and 90) labeled axons with numerous terminals and en passant boutons throughout the deeper layers of the SC. This labeling covered the entire mediolateral extent of the SC, but, in keeping with the pattern of retrograde labeling following microsphere injections in the SC, was more restricted rostrocaudally. No systematic changes were observed with age. The stability of the nBIC-SC projection over this period suggests that developmental changes in auditory spatial tuning involve other processes, rather than a gross refinement of the projection from the nBIC.     

Mechanisms of the suppression of the nociceptive reflex of the opening of the mouth during stimulation of the structures of the limbic brain

The comparative effectiveness of the inhibitory influence of tetanic stimulation of hypothalamus, amygdala and limbic cortex on EMG-response of m. digastricus evoked by electrical stimulation of tooth pulp nociceptive afferents was studied in cats anesthetized with a mixture of chloralose and nembutal. It was found that inhibition of the EMG-component of the jaw-opening reflex is most pronounced in case of stimulation of medial and lateral region of the hypothalamus, the inhibitory effect of central and medial nuclei of the amygdala is less pronounced and the effect of the limbic cortex is the weakest. It was shown that the mechanism of the antinociceptive effect of tetanic stimulation of the hypothalamus is not related to the concomitant increase of the blood pressure. After stabilization of the blood pressure the suppressive effect of the hypothalamus remains without changes, that points out to a direct, primary, not baro-afferent mechanism of the inhibition of the activity of nociceptive neurons of the trigeminal sensory nuclei. Noradrenaline, injected intravenously, induced a large increase of the blood pressure accompanied by a pronounced inhibition of the pain reflex. Angiotensin causes the same degree of blood pressure elevation without changes in the amplitude of the EMG-response of the pain reflex. Hypothalamic and noradrenergic mechanisms for control of pain sensitivity are discussed.     

Origins of the sympathetic innervation of the cervical end of the uterus in the rat

A retrograde neuronal tracer (Fast Blue) was injected in the cervical end of the uterine horn of virgin rats. The majority of the retrogradely labeled post-ganglionic sympathetic neurons were found in the sympathetic chain (74%). The superior mesenteric ganglia, inferior mesenteric ganglia and suprarenal ganglia accounted for 22, 3 and <1%, respectively. The distribution of neurons in the sympathetic chain labeled from the uterus resembles that described for other pelvic organs.     

Sexual pheromones and the evolution of the reward system of the brain: the chemosensory function of the amygdala

The amygdala of all tetrapod vertebrates receives direct projections from the main and accessory olfactory bulbs, and the strong similarities in the organization of these projections suggest that they have undergone a very conservative evolution. However, current ideas about the function of the amygdala do not pay sufficient attention to its chemosensory role, but only view it as the core of the emotional brain. In this study, we propose that both roles of the amygdala are intimately linked since the amygdala is actually involved in mediating emotional responses to chemical signals. The amygdala is the only structure in the brain receiving pheromonal information directly from the accessory olfactory bulbs and we have shown in mice that males emit sexual pheromones that are innately attractive for females. In fact, sexual pheromones can be used as unconditioned stimuli to induce a conditioned attraction to previously neutral odorants as well as a conditioned place preference. Therefore, sexual pheromones should be regarded as natural reinforcers. Behavioural and pharmacological studies (reviewed here) have shown that the females' innate preference for sexual pheromones is not affected by lesions of the dopaminergic cells of the ventral tegmental area, and that the systemic administration of dopamine antagonists do not alter neither the attraction nor the reinforcing effects of these pheromones. Anatomical studies have shown that the vomeronasal amygdala gives rise to important projections to the olfactory tubercle and the islands of Calleja, suggesting that these amygdalo-striatal pathways might be involved in the reinforcing value of sexual pheromones.     

药物治疗与合并认知行为治疗对强迫症疗效的比较

目的探讨认知行为心理治疗(CBT)在强迫症(OCD)患者各亚型治疗中的有效性和规律性。方法本研究为临床对照研究。符合入组标准的强迫症患者按患者自愿原则分为两组,治疗观察3、6、12个月。疗效评定分别运用Yale-Brown强迫量表,自拟的自评好转程度量表和临床疗效评定。结果认知行为心理治疗合并药物治疗组31例,临床有效率70.9%,其中治愈率1.8%。单纯药物治疗组24例,临床有效率33.3%。Yale-Brown强迫量表和自评量表得分在6个月和12个月两组有显著差异(P<0.05)。其中强迫症亚型(怕脏型、反复检查型和反复担心型)的疗效比较,怕脏型在治疗3个月末两组间自评量表评分有显著性差异(P<0.05);反复担心型在治疗6个月末两组间Yale-Brown强迫量表总分有显著性差异(P<0.05);反复检查型两组间无统计学差异。结论认知行为心理治疗合并药物治疗强迫症的疗效明显优于单纯药物治疗。强迫症的亚型在治疗中的有效性次序为:反复担心型>怕脏型>反复检查型。     

Topographical organization of the motoneuron pools that innervate the muscles of the pinna of the cat

The topographical organization of the 22 motoneuron pools that innervate the pinna muscles of the cat was examined by injecting the B-subunit of cholera toxin conjugated to horseradish peroxidase into individual muscles. All 22 pools are found in the facial nucleus, organized as rostro-caudally oriented columns, and arranged according to the action of the muscles they innervate. Pools innervating muscles that pull the pinna dorsally are located in the dorsal two thirds of the medio-dorsal subdivision, and those innervating muscles that pull the pinna ventrally are located in the ventral one half of the nucleus. Motoneurons innervating muscles that pull the pinna cranially are located laterally, those that pull the pinna caudally are located medio-ventrally, and those that change the shape of the pinna are located along the entire dorso-ventral extent in the center of the medio-dorsal subdivision. This topographical layout is consistent with the somatotopic organization of the entire facial nucleus as demonstrated in a variety of species. © 1995 Wiley-Liss, Inc.     

Histochemical methods for the further characterisation of the tumourettes of the posterior lobe of the pituitary

Summary The granular cell tumourettes of the posterior lobe of the pituitary possess neuraminic acid containing carbohydrate. After removal of neuraminic acid with neuraminidase and exposure to FITC (Fluorescein isothiocyanate) labelled peanut agglutinin (Arachis hypogaea) (PNA), intracellular receptor structures could be demonstrated. The significance of the findings is discussed.