不同脑区小胶质细胞异常影响精神分裂症发病的研究进展

精神分裂症是一种常导致患者精神活动严重受损的重型精神障碍, 病因及病理机制仍待进一步阐明。不同脑区的炎症及损伤与精神分裂症的病理过程存在关性, 而小胶质细胞正是这些炎症损伤过程中的活跃参与者。本文就小胶质细胞对神经发育和可塑性的影响, 以及异常激活状态下通过介导不同脑区损伤参与精神分裂症的发病作一综述。     

小胶质细胞参与自闭症谱系障碍的神经生物学机制

自闭症谱系障碍（ASD）病理机制复杂,神经与免疫系统功能异常在自闭症病理生理机制研究中占重要地位。小胶质细胞是中枢神经系统发育和内稳态不可缺少的协调者。遗传或环境因素导致胎儿及发育早期小胶质细胞介导的突触修剪和免疫反应异常的病理改变,可能参与ASD的发病过程。本文重点从小胶质细胞参与自闭症的突触修剪、神经免疫相关文献作一综述,探讨小胶质细胞参与ASD的神经生物学机制和潜在的治疗靶点。     

小胶质细胞极化在肌萎缩侧索硬化发病中的作用研究进展

肌萎缩侧索硬化(amyotrophic lateral sclerosis, ALS)是一种神经系统慢性进行性变性疾病，其病因及发病机制仍不明确。越来越多证据表明，免疫异常及神经炎症与ALS的发病密切相关，其中小胶质细胞的极化作为神经炎症研究重要组成部分，其与ALS发病及进展密切相关，深入研究小胶质细胞极化在ALS中的作用机制可能为ALS的临床诊断、靶向干预治疗提供线索和思路。现就小胶质细胞极化在ALS发病中的作用研究进展进行综述。     

小胶质细胞在创伤性脑损伤后癫痫中的作用研究进展

创伤性脑损伤(TBI)是一种严重威胁人们生命健康的疾病, 而TBI后癫痫(PTE)是其严重的后遗症之一。由于PTE发生的病理生理机制尚未阐明, 目前尚无有效的预防和治疗方法。TBI触发了强烈且持久的炎症级联反应, 提示神经炎症可能与PTE的发病机制有关。而小胶质细胞, 作为大脑中最常见的免疫细胞, 在神经炎症中发挥着重要作用。小胶质细胞在TBI后被激活, 可表达促炎或抗炎等表型。不同的极化状态与各种促炎或抗炎型介质的释放有关, 且不同程度上影响着大脑的修复和PTE的发生与发展。鉴于不同表型的小胶质细胞在神经炎症中发挥的作用不同, 调节小胶质细胞的极化方向可能对TBI和PTE患者的治疗具有重要意义。本文综述了TBI后不同时间点小胶质细胞的表型和功能, 深入探究小胶质细胞极化的信号通路和导致癫痫发生的潜在机制, 以及总结了防治TBI和PTE的药物研究进展, 以期为PTE动物实验的临床转化奠定基础。     

胶质细胞在癫癎发病机制中的作用研究进展

癫癎是神经系统疾病中的一种严重危害人类健康的常见病、多发病,患病率约为1%,发病机制非常复杂.胶质细胞是神经系统的重要组成部分,胶质细胞占脑细胞总数的约90%,包括星形胶质细胞、少突胶质细胞和小胶质细胞,其在生理与病理状态下对维护神经系统功能的作用至今未明.胶质细胞不仅与脑的正常生理活动、发育以及神经病理过程有明显关系,而且与神经元的功能活动以及损伤与修复过程有千丝万缕的联系.近年来研究表明胶质细胞在癫癎的发病机制中扮演重要角色.本文就癎性发作时胶质细胞功能改变(细胞形态改变、免疫表型改变和细胞增殖活动)、胶质细胞与神经元之间物质、信息交流方面的研究进展进行综述.     

胶质细胞在癫痫发病机制中的作用研究进展

癫痫是神经系统疾病中的一种严重危害人类健康的常见病、多发病，患病率约为1％，发病机制非常复杂。胶质细胞是神经系统的重要组成部分，胶质细胞占脑细胞总数的约90％，包括星形胶质细胞、少突胶质细胞和小胶质细胞，其在生理与病理状态下对维护神经系统功能的作用至今未明。胶质细胞不仅与脑的正常生理活动、发育以及神经病理过程有明显关系，而且与神经元的功能活动以及损伤与修复过程有千丝万缕的联系。近年来研究表明胶质细胞在癫痫的发病机制中扮演重要角色。本文就痫性发作时胶质细胞功能改变（细胞形态改变、免疫表型改变和细胞增殖活动）、胶质细胞与神经元之间物质、信息交流方面的研究进展进行综述。     

米诺环素在精神分裂症治疗中的研究进展

越来越多的证据表明小胶质细胞活化介导的神经炎症在精神分裂症病因中起着重要的作用。米诺环素能够抑制小胶质细胞的活化,它具有抗炎、抗氧化、抗凋亡等多种特性,近年来,米诺环素在精神分裂症中治疗研究逐渐开展,本文就其作用机制及研究进展作一综述。     

小胶质细胞在癫痫中作用的研究进展

正癫痫是神经元突发、异常、过度、同步放电引发的一种发作性脑功能障碍。癫痫发病机制十分复杂。研究发现神经炎症、氧化应激、免疫失调、神经元凋亡、自噬等因素,在癫痫发病过程中发挥重要作用。小胶质细胞是中枢神经系统的免疫效应细胞,参与将神经炎症、氧化应激、神经元凋亡、免疫调节等。本文就小胶质细胞在癫痫中的作用进行综述。1小胶质细胞的概述1.1小胶质细胞的类型与功能小胶质细胞外形和蛋白表达存在差异,不同条件激活的类型和功能状态也有差异[1]。小胶质细胞处于静息状态时体积较小,呈梭状,有树枝状分支;激活后,细胞体积变大,     

IL-4调控小胶质细胞极化在血管性认知障碍中的作用机制研究进展

血管性痴呆（vascular dementia,VD）的核心症状是认知功能障碍。大脑缺血后小胶质细胞被激活,进而诱导神经炎症反应是血管性认知功能障碍发生的关键。既往部分研究认为,小胶质细胞在病理状态下主要发挥促炎作用,但近年来越来越多的研究发现,小胶质细胞极化后的不同表型可发挥不同的作用,提示小胶质细胞极化在VD机制研究中的重要地位。白细胞介素-4(interleukin-4,IL-4)作为诱导小胶质细胞从促炎的M1表型极化到抗炎的M2表型的重要调节因子,已被证明与学习认知的病理过程密切相关。本文着重对小胶质细胞极化在血管性认知障碍中的研究进展及IL-4在小胶质细胞极化转化过程中的作用机制进行综述,以期为血管性痴呆的治疗提供新的思路。     

microRNAs调控小胶质细胞极化在神经炎症中的作用

microRNAs(miRNAs)是一类长度约为19-25个核苷酸稳定的内源性小分子非编码RNA,小胶质细胞是广泛分布于中枢神经系统的常驻免疫细胞,miRNAs与小胶质细胞的极化有着密切的关系。本文综述近年来促炎型/抗炎型miRNAs调控小胶质细胞M1型/M2型极化及其在相关炎症介导的神经系统疾病中的研究进展,充分阐明小胶质细胞极化过程中miRNAs调控机制,为寻找治疗与小胶质极化相关炎症介导的神经系统疾病的新靶点提供了有力的理论依据。     

Inhomogeneities in the propagation of the slow wave in the stomach

The propagation of the slow wave in the stomach and its role in inducing sweeping peristaltic contractions toward the pylorus, essential for a proper digestion and emptying, have been studied for many years. Irregularities in the timing or in the pattern of propagation of the slow wave have been known to induce various gastric malfunctions and, recently, several types of gastric dysrhythmias have been described which could lead to gastric contraction abnormalities. In this study, Du et al. have analyzed the disturbances caused by a simple transmural incision in a human stomach, performed to obtain a biopsy of the muscle, on the propagation pattern of the slow wave. In addition, they show that such an incision may by itself also induce new types of gastric dysrhythmias. These results are important in demonstrating that the function of the stomach can easily be disturbed by such procedures. This mini‐review describes several ways in which inhomogeneities in propagation may affect the conduction pattern of the slow wave, including the genesis of several dysrhythmias, and what is currently known about their impact on gastric contraction and digestion.     

Early stages in the formation of the cerebellum in the frog

The formation of the cerebellum was studied during the first 6 months of the tadpole stage of the bullfrog by using standard histological methods and reconstructions from serial horizontal sections. Three major developmental phases were noted in the formation of the cerebellum. (1) During the first 5 weeks of development, the neuroepithelium proliferated and the dorsal mesencephalic plates increased in size. (2) Starting in the sixth week, a patch of neuroepithelium began to differentiate and gave rise to a small population of Purkinje cells. In subsequent weeks, the area of differentiation continued to spread and a Purkinje cell layer became established along the dorsal margin of the cerebellar plate. (3) In the 12th week, the ventrolateral part of the cerebellar plate began to increase in size and generate two populations of small cells. The lateralmost part of the neuroepithelium in this area generated a group of cells that formed an external granular layer that was one cell deep. Cells of this external granular layer migrated inward into the primitive molecular layer, and by the 26th week only a remnant of an external granular layer remained in the cerebellum. The more medially situated part of the neuroepithelium gave rise to another population of small cells that formed a column, which appeared to be continuous with the Purkinje cells, but differed from them in size. It should be noted that full maturation of the cerebellum occurs during metamorphosis, which in this species remains some 2 years away.     

Local nonuniformities in the syncytium of the horizontal cells of the retina in the turtle

Electrical coupling between horizontal cells of the turtle retina was investigated by means of two microelectrodes (current and recording ones) penetrating neighbouring cells at a fixed distance from each other. The morphological coupling was revealed by means of fluorescent dye Lucifer Yellow. The electrical coupling was confirmed between elements of similar type (L1--axonal terminals, or L2--cell bodies, or R/G type cells) and no coupling was found between elements of different types, though L1 and L2 are directly connected through thin axons. In the L1 syncytium the electrical coupling at small (less than or equal to 50 microns) but fixed distances between microelectrodes could differ several times depending on the minimal displacement of microelectrodes. This local nonuniformity of coupling can be explained on the basis of structural nonuniformities in the L1 (axon terminal) network. It is unlikely however that the structural nonuniformities can influence the functional properties of horizontal cell network when the retina is stimulated adequately (by light).     

Asymmetry in the structural organization of the ganglion layer of the retina in the frog

Silver-impregnated retinal preparations were used to study the distribution density and topographic features of small and large ganglionic cells (GC) of Rana ridibunda and Rana temporaria. For both species the increased density of GC (a streak) stretched higher than the naso-temporal axis passing through the optic disk. Beyond the streak the density of small GC was maximal in the central zone of the retina and decreased towards its periphery. For the upper quadrants of the retina the density of small GC was higher than that for the lower ones by 26% on the average. On the contrary, the density of large GC was higher in the lower part of the retina as compared to the upper one, the difference being more pronounced for R. temporaria. The density of large GC was also asymmetric with respect to the dorso-ventral axis being higher in nasal quadrants than in temporal ones by 40-55%. The highest density of large GC was found in the middle zone of the retina. The found structural asymmetry in the retinal output raster may bear an adaptively ecological meaning and may condition the particularities of the formation of the visually guided prey-catching and avoidance reactions.     

Challenges in the Management of the HIV Patient in the Third Decade of AIDS

The epidemic of AIDS has been increasingly recognized as a major health and socioeconomic problem, not only in the United States or Africa, but also the rest of the world. The face of the epidemic has changed. The role that mental health providers play has also significantly grown as the epidemic continues on. Prior to the introduction of Highly Active Anti-Retroviral Therapy (HAART) and other advances in HIV care, the patients faced issues that related to death and dying. These advances brought with them renewed hope and resurrected lives. The patients fought with issues related to living new lives with HIV no longer an imminent death threat. In the third decade of AIDS, the struggles of the post-HAART era continue but bring with it more challenges. Mental health providers need to familiarize themselves with these issues so that they can better help HIV patients cope with this devastating disease.     

Role of the subthalamo-nigral input in the control of amygdala-kindled seizures in the rat

The substantia nigra pars reticulata (SNpr) is a critical site for the control of epileptic seizures. Potentiation of the inhibitory GABAergic input from the striatum to the SNpr suppresses primary or secondary generalized seizures in the rat. The purpose of this study was to examine the possible involvement of the excitatory glutamatergic input from the subthalamic nucleus to the SNpr in the control of both the electroencephalographic and the motor components of amygdala-kindled seizures in the rat. Microinjections of either an N-methyl- -aspartate (NMDA) antagonist in the substantia nigra or a GABA_A agonist in the subthalamic nucleus, significantly reduced motor seizures but did not modified the afterdischarges. These results provide evidence for the involvement of the subthalamo-nigral projection in the modulation and the propagation of the motor components of amygdala-kindled seizures.     

Patterning in the regeneration of electroreceptors in the fin of Kryptopterus

The influence of the target tissue on afferent nerve regeneration was studied in the adult glass catfish, Kryptopterus. In this fish, electroreceptors in the anal fin are distributed in a characteristic pattern in the proximal part of the fin and are absent in the distal portion of the fin. We tested whether axons were more likely to induce electroreceptors in certain regions of fin epidermis than in others. We rotated fin transplants so that the location of the degenerating electroreceptors was altered with respect to the regenerating axons in the host tissue dorsal to the fin. The effects of these rotations were observed in the living animal with differential interference contrast optics over a period of 10 weeks. When transplants were reversed rostrocaudally, new electroreceptors formed in the caudal half of the interradial zone, where degenerating electroreceptors were at the time of transplantation. When transplants were rotated so that the dorsoventral and rostrocaudal axes were reversed, some new receptors formed in the old target site regions that were located in the caudal interradial zones (in the distal half of the graft with respect to the host). Regenerating axons reached these regions of the transplant by taking unusual routes around the electroreceptor-free regions of fin. Very few electroreceptors formed in the distal/caudal or proximal/caudal interradial quadrants of grafts where the original orientation of the tissue was maintained. We suggest that old target sites have a neurotropic influence on the regenerating afferent axons and discuss the possibility that the distal fin epidermis is not as permissive to electroreceptor formation as proximal fin epidermis.     

Organization in the descending tracts of the dorsolateral funiculus in the cat

Organization of the fibers in the descending tracts of the dorsolateral funiculus of the cervical spinal cord was investigated in cats. The spinal cord was penetrated with microelectrodes at 400 mum intervals in the medio-lateral direction at the c5/c6 and c6/c7 segmental borders. Silicon substrate microelectrodes with a linear arrangement of activated iridium contacts were used. The stimulus consisted of a 20 ms train of charge balanced biphasic current pulses at 330 Hz. The evoked activities from selected forelimb muscles were acquired into computer. Only the data points with an activation threshold of less than 35 muA were considered in the analysis. Muscle contractions were mostly in the form of short twitches. In both spinal segments, an area of high threshold was found in the middle of the dorsolateral funiculus. Majority of the muscles studied had a dorsal or ventral concentration of activation points. The distal muscles were mostly activated in the ventro-lateral aspect of the funiculus, while the elbow muscle maps spread to both dorsal and ventral sides. These results show a functional organization in both cervical segments studied, with overlapping regions between the areas dedicated for each forelimb muscle.     

Pursuit of the origin of the large myelinated fibers of the anterolateral funiculus in the spinal cord in humans in relation to the pathomechanism in amyotrophic lateral sclerosis

To determine the origin of the large myelinated fibers in the anterolateral funiculus (ALF) in the spinal cord of humans, myelinated fibers in the ALF of the mid-cervical spinal cord were examined quantitatively. Five groups of subjects were examined, consisting of control subjects, patients with cerebral lesions and showing complete degeneration of the unilateral/bilateral pyramis of the medulla oblongata, those with lesions of the pontine tegmentum, those with lesions of the lower cervical spinal cord, and those with thoracic/lumbar lesions. The results indicate that the large myelinated fibers in the ALF of the mid-cervical spinal cord of humans originate from the tegmentum of the brain stem and the lower cervical spinal cord, and not from the cerebrum, or the thoracic or lumbar spinal cord. Thus, they are descending fibers from the brain stem tegmentum and ascending fibers from the lower cervical cord, and not corticospinal tracts or long-ascending fibers from the thoracic or lumbar spinal cord. The origin of the large myelinated fibers in the ALF of the spinal cord in humans, the number of which was severely decreased in patients with amyotrophic lateral sclerosis, is considered to be the long-descending neurons in the brain stem tegmentum and the propriospinal neurons in the spinal cord. Received: 23 December 1998 / Revised, accepted: 29 March 1999     

Selectivity between faces in the responses of a population of neurons in the cortex in the superior temporal sulcus of the monkey

There is a population of neurons in the cortex in the middle and anterior part of the superior temporal sulcus (STS) of the monkey with responses which are selective for faces. If, consistent with the effects of damage to the temporal lobe, these neurons are involved in face recognition or in making appropriate social responses to different individuals, then it might be expected that at least some of these neurons might respond differently to different faces. To investigate whether at least some of these neurons do respond differently to different faces, their responses were measured to a standard set of faces, presented in random sequence using a video framestore. It was found that a considerable proportion of the neurons with face selective responses tested (34/44 or 77%) responded differently to different faces, as shown by analyses of variance. An index of the discriminability of the most and least effective face stimulus (d') ranged between 0.2 and 5.0 for the different neurons. Although these neurons often responded differently to different faces, they did not usually respond to only one of the faces in the set, so that information that a particular face had been shown was present across an ensemble of neurons, rather than in the responses of an individual neuron. These findings indicate that the responses of these neurons would be useful in providing information on which different behavioral responses made to different faces could be based. These neurons could thus be filters, the output of which could be used for recognition of different individuals and in emotional responses made to different individuals.