星形胶质细胞在脑白质缺血性损伤后髓鞘再生的研究进展

脑白质损伤可导致认知功能障碍、情感障碍、感觉运动障碍等,是神经功能预后不良的危险因素。脑白质缺血损伤相关机制复杂,主要可引起少突胶质细胞死亡以及脱髓鞘改变。成熟的少突胶质细胞死亡主要通过少突胶质前体细胞的分化来进行补充。因此,促进少突胶质前体细胞分化及髓鞘再生是缺血性损伤后白质完整性重塑的重要因素。星形胶质细胞是少突胶质谱系细胞外环境的组成部分,可以直接影响少突谱系胶质细胞的存活及功能,在神经损伤修复及髓鞘再生方面均发挥重要作用。本文主要评述了髓鞘损伤相关机制以及星形胶质细胞从多个方面影响髓鞘损伤及恢复的作用及机制,为白质损伤后的髓鞘再生提供一定的理论依据。     

NG2胶质细胞的研究进展

NG2是一种硫酸软骨素蛋白多糖(chondroitin sulphate peoteoglycan,CSPG),早期发现在成年大鼠脊髓和大脑的一群成熟胶质细胞中表达,根据这些细胞在白质和灰质中的形态特征,把它们命名为原浆型星形胶质细胞(protoplasmic astrocyte)[1].在发育早期脑内培养的胶质细胞中,有一种叫少突胶质-Ⅱ型星形胶质细胞(O-2A cells)的细胞类型也能被NG2抗体标记[2,3].     

Oligodendrocytes in Mouse Corpus Callosum are Coupled Via Gap Junction Channels Formed by Connexin47 and Connexin32

已有的超微结构研究显示,白质中的少突胶质细胞和星形胶质细胞之间存在缝隙连接,但少突胶质细胞之间不存在缝隙连接,虽然体外培养的少突胶质细胞可形成功能性缝隙连接。本文研究新生小鼠胼胝体急性脑片中的少突胶质细胞的功能性连接。以全细胞膜片钳技术用生物胞素(一种可渗透的缝隙连接示踪剂)标记少突胶质细胞。平均61个细胞为链霉亲和素-Cy3标记的生物胞素阳性。约77%的连结细胞表达少突胶质细胞标志蛋白CNPase阳性染色,9%表达星形胶质细胞标志蛋白GFAP阳性,14%为CNPase和GFAP阴性。后者的大部分表达Olig2和一些NG2(少突胶质细胞前体细胞的标志物)。少突胶质细胞表达Cx47、Cx32和Cx29,星形胶质细胞表达Cx43和Cx30。在Cx47敲除小鼠中,连结细胞的数量减少80%。单独删除Cx32或Cx29并不能显著减少连结细胞的数量,但Cx32/Cx47双缺陷小鼠中没有观察到相互连结的细胞。Cx47敲除完全消除了少突胶质细胞与星形胶质细胞间的耦联。在Cx43敲除动物中,少突胶质细胞-星形胶质细胞间连接仍然存在,但与少突胶质细胞前体细胞间的耦联没有被观察到。在Cx43/Cx30双敲除小鼠中,少突胶质细胞-星形胶质细胞连接几乎不存在。解开连结的少突胶质细胞显示为较高的膜输入电阻。本文认为,白质中的少突胶质细胞依靠Cx47和Cx32的表达形成功能性的合胞体,而星形胶质蛋白缝隙连接蛋白的表达能提升此网络的大小。     

Role of the Oligodendroglial Cytoskeleton in Differentiation and Myelination

少突胶质细胞作为中枢神经系统的髓鞘形成细胞,在体外培养时形成一个精细的突起网络,细胞生长并中止于富含髓鞘相关蛋白和脂质的膜层。在体的少突胶质细胞呈螺旋形包裹轴突形成一个紧密的绝缘层。与其它细胞相似,这些突起的维持和稳定以及髓鞘的形成可能依赖于一个由微管和微丝构成的细胞骨架。尽管包裹轴突、形成紧密髓鞘的特定突出尚不明确,但是已有相当的研究考察少突胶质细胞分化和髓鞘形成过程中细胞外和细胞内信号及其他作用因子介导细胞骨架的形成,在此,我们综述了细胞骨架在少突胶质细胞分化的作用,重点探讨了相关信号转导机制,并就其在髓鞘形成中重要意义予以展望。     

神经细胞与NG2胶质细胞的突触联系

NG2胶质细胞是少突胶质细胞的前体,它们与神经细胞有突触联系。NG2胶质细胞具有高度分枝的形态,从细胞体辐射出大量的轴突,并表达一系列复杂的电压门控通道。神经细胞-NG2胶质细胞突触在分化为髓鞘化的少突胶质细胞中及调控神经细胞网络系统活动方面起着重要作用。     

Artifact Versus Reality-How Astrocytes Contribute to Synaptic Events

一个世纪前发展的神经元学说,认为神经元网络是维持高级大脑功能的唯一细胞类型。胶质细胞生理学的最新进展,促进了另一种假说的提出,它认为大脑信息处理通过神经元-胶质细胞网络利用双重的(神经元动作电位)和同类的(第二信使/代谢物通过缝隙连接或递质在细胞间隙的扩散传播)信号编码来完成。这两种神经细胞间存在前馈和反馈通信,引起信息传递和处理,是通过神经元终端和星形胶质细胞突起的神经递质释放来完成。然而,对这个问题的认识,仍然是不完整的。一些重要的问题和争议有待解决。本文认为,突触旁的胶质细胞突起的主要功能是创建一个"星形胶质细胞摇篮",以保护突触免受大量来自突触外的信号活动的作用,并通过多种机制为突触联系提供多方面的支持和长期的可塑性保护,这些过程并不一定涉及胶质源性神经递质的释放。     

嘌呤能信号在少突胶质细胞发育和髓鞘修复中的作用及机制研究进展

少突胶质细胞（OL）是发育中的中枢神经系统（central nervous system,CNS）髓鞘形成和髓鞘损伤再生的关键;ATP不仅是一种能量载体,也作为一个重要的信号分子参与细胞之间的交流,其嘌呤能受体亚型广泛存在于神经元和神经胶质细胞中,主要包括接受腺苷信号的P1受体和接受ATP/ADP/UTP信号的P2受体。不同亚型的嘌呤能受体在CNS中不同部位的表达及其在生理病理状态下发挥的具体作用和机制也各有不同,本文对近年来关于嘌呤能受体在OL发育及髓鞘形成与修复中作用和机制研究的新进展进行综述,该方面的研究对于了解嘌呤能信号在诸多脱髓鞘性疾病以及髓鞘发育障碍性疾病中的作用、发掘相应的潜在治疗靶点具有重要的意义。     

Quantification of Oligodendrocyte Progenitor Cells in Human and Cat Optic Nerve:Implications for Endogenous Repair in Multiple Sclerosis

促进来源于少突胶质祖细胞(OP)的少突胶质细胞髓鞘再生,提高内源性修复是改善多发性硬化运动障碍的重要方法之一,其重要前提是明确人类中枢神经系统中有丰富的可分化为少突胶质细胞的OP细胞,而这需要有对中枢神经系统中的OP细胞进行鉴定的可靠方法。本研究采用多种方法对猫和人的视神经进行染色,根据相关结果获取可用于研究人尸体解剖标本OP细胞表达的抗原表型。OP细胞又被称为NG2细胞,广泛表达NG2蛋白,属于一个独立的胶质细胞亚型,由于其表达OP细胞系的转录因子Olig1和Olig2,因此与少突胶质细胞相关。虽然NG2细胞形态多样,与轴索及其它胶质细胞紧密联系,但所有NG2细胞都可以作为OP细胞进行分化,补充局部丢失的少突胶质细胞。研究发现,在人和猫的视神经及猫脊髓的白质和灰质中,NG2细胞在神经胶质细胞中所占比例不足5%,与少突胶质细胞的比例为1∶10。本研究结果显示,NG2细胞数量特别是相对少突胶质细胞不充足,这可对促进多发硬化内源性修复的方法提供线索。     

从髓鞘脱失到髓鞘再生:脊髓损伤的治疗之路

髓鞘完整性是维持中枢神经系统的生理功能的重要因素,脊髓损伤后髓鞘完整性的保存和再生对于脊髓功能的恢复有关键性的作用。脊髓损伤后,郎飞氏结等结构破坏,轴索暴露,髓鞘脱失处的神经传导受阻。之后出现少突胶质细胞丢失及髓鞘溶解等进一步的损伤。本文对少突胶质细胞丢失及髓鞘溶解的主要生物学事件及机制进行综述,并探讨抑制这些过程的方法。促进内源性的髓鞘再生是脊髓损伤后修复另外一个重要方面。最近研究发现在髓鞘再生过程中,先天性免疫和自适应免疫具有多重作用,胶质疤痕也可能具有潜在的免疫调节作用。神经元活化、少突胶质细胞生成及髓鞘形成间的紧密联系提示髓鞘恢复对脊髓功能的修复有重要意义。在临床应用中,已有几种治疗方案将脊髓损伤的病理生理作为修复目标,包括基因调控、小分子治疗、免疫调节、调控胶质疤痕以及细胞移植。一些新技术也已经开始尝试用于脊髓损伤的治疗,如通过细胞编程将一种细胞转变为另一种细胞、纳米或组织工程技术等。脊髓损伤后脊髓组织的损伤情况是复杂多样的,因此在治疗中需要使用综合性的手段,在损伤后早期尽快修复少突胶质细胞和髓鞘,促进髓鞘再生,为临床应用打基础。     

星形胶质细胞和嗅鞘细胞之间的Panglial缝隙连接介导Ca~(2+)瞬变的传递和神经血管耦合

星形胶质细胞排列在有高度组织性的缝隙连接耦合网络中,通过Ca~(2+)波的传播进行通信。星形胶质细胞不仅与邻近的星形胶质细胞结合,而且还与少突胶质细胞偶联,形成panglial合胞体。但panglial合胞体中的神经胶质细胞是否通过Ca~(2+)信号传递信息尚不清楚。我们使用共聚焦Ca~(2+)成像来研究小鼠嗅球中星形胶质细胞和嗅鞘神经胶质细胞(OECs)之间的细胞间通讯。研究结果表明,通过"笼状" ATP和"笼状" tACPD的局部光解可引起的肾小球旁星形胶质细胞中的Ca~(2+)瞬变,导致OEC中随之而来的Ca~(2+)反应。这种从星形胶质细胞到OEC的Ca~(2+)反应的传递在神经元抑制的情况下持续存在,但是当用甘珀酸抑制缝隙连接偶联时消失。当通过DHPG的抽吸在OEC中直接诱发Ca~(2+)瞬变时,它们导致肾小球星形胶质细胞中的Ca~(2+)反应延迟,表明Ca~(2+)信号的panglial传递以双向方式发生。此外,从星形胶质细胞到OEC的Ca~(2+)信号的panglial传递导致嗅觉神经层中OEC相关血管的收缩。本研究结果证明了在缝隙连接耦合的panglial网络中,不同类别的神经胶质细胞之间通过Ca~(2+)进行信号传递,并借此调节嗅球中血管的直径。     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.     

俯卧位通气对高海拔地区肺复张治疗无效急性呼吸窘迫综合征患者氧合的影响

目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高＜20％视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P＜0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P＜0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P＜0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.     

Digital imaging among medical facilities

The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.     

Myocardial elastography at both high temporal and spatial resolution for the detection of infarcts

Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.     

Clinical Pharmacokinetics of Morphine

Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is the standard against which new analgesics are measured. A thorough understanding of the pharmacokinetics of morphine is required in order to safely and effectively use this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and January 2002 relevant to the pharmacokinetics of morphine. These publications were reviewed and the literature summarized regarding unique and clinically important elements of morphine disposition relative to its parenteral administration (including intravenous, intramuscular, subcutaneous, epidural and intrathecal administration), absorption profile (immediate release, controlled release, and sublingual/buccal, and rectal administration), distribution, and its metabolism/ excretion. Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.