小胶质细胞在中枢神经系统疾病血管新生中的作用

小胶质细胞是中枢神经系统(CNS)的免疫细胞,监视CNS免受损伤在神经发育过程中也起着重要作用.血管新生在缺血性脑卒中和肿瘤等疾病中发挥着重要作用,调控血管新生已成为这些疾病的潜在治疗靶点.在神经发育及CNS疾病的发生、发展过程中,小胶质细胞与血管新生均有着密切联系.然而,目前对于小胶质细胞在CNS疾病血管新生中的作用...     

小胶质细胞的活化与调控

小胶质细胞在中枢神经系统(CNS)中起重要作用，与CNS的生理功能和病理过程密切相关。小胶质细胞的活化和调控过程涉及多种因素，如细胞因子、某些蛋白质和酶、细胞内外离子和电位的变化等。     

胶质微环境与中枢神经系统损伤修复

中枢神经系统(central mervous system,CNS)损伤包括腩损伤和脊髓损伤,致残率和病死率较高.因此,CNS损伤修复一直是神经科学领域的一个研究重点和热点.成年哺乳动物神经元的内在再生能力有限是CNS损伤后再生困难的原因之一,但更为重要的原因是损伤局部抑制性胶质微环境的形成.文章就胶质微环境内星形胶质细胞、小胶质细胞、少突胶质细胞等各类组成细胞在CNS损伤修复中的作用做了综述.     

小胶质细胞参与间歇低氧对中枢神经系统神经元的损伤

阻塞性睡眠呼吸暂停（obstructivesleepapnea,OsA）是一种以睡眠期间上气道反复发生完全（呼吸暂停）或部分（低通气）阻塞导致低氧血症和夜间反复觉醒为特征的常见慢性疾病。0SA所造成的间歇低氧（IH）可导致中枢神经系统（CNS）结构性神经元损伤与功能障碍,在临床上表现为神经认知与行为障碍,其主要病生理基础在细胞水平上可被归为小胶质细胞为主的氧化应激和炎性损伤。小胶质细胞是CNS中主要的炎症细胞,通过线粒体、NADPH氧化酶以及兴奋性神经毒性递质的释放来引发CNs氧化应激和炎症。小胶质细胞为主的炎症过程是把双刃剑,神经毒性与神经保护之间、炎症与抗炎小胶质细胞细胞因子之间的平衡决定了小胶质细胞在OSAIH暴露后最终扮演的角色。小胶质细胞炎性损伤一旦启动,可能会持续不停并级联放大,最终导致有临床意义的CNs神经元损伤。本文将综述OSAIH对CNS结构性神经元的损伤极其并发的功能障碍,以及在小胶质细胞可能发挥的作用及其可能机制。     

蛋白激酶MST1与中枢神经系统疾病关系的研究进展

正中枢神经系统(CNS)是人体神经系统的主要部分,包括脑和脊髓两部分。CNS负责全身各处信息的接收、整合、加工及传出。神经细胞凋亡坏死、氧化损伤、炎症反应、缺血、脱髓鞘、星形胶质细胞与少突胶质细胞的兴奋性毒性作用,轴突和基因的改变等多种病理生理学机制参与CNS疾病的发生发展过程~[1,2]。CNS的这些改变通常会引起意识、认知、运动、感觉及平衡障碍等多种临床表现,甚至出现死亡。神经元细胞无法再生,这给CNS损伤的患者留下了局限的治疗方案     

急性胰腺炎时血脑屏障通透性变化规律及其与胰腺病变的关系

胰性脑病是急性胰腺炎的重要并发症，其临床发生率为3％～27％，而死亡率高达40％以上。血脑屏障是中枢神经系统（CNS）的重要保护机制，它能保护大脑免受外周致病因子的攻击。血脑屏障的损伤和通透性升高是多种CNS炎症及病变的前提。胶质纤维酸性蛋白（GFAP）是星形胶质细胞的标志蛋白，由各种原因引起的CNS损伤均可引起星形胶质细胞活化、GFAP表达增加，因此GFAP表达水平可以作为CNS损伤程度的标志。     

肠道神经胶质细胞在炎症性肠病研究中的新进展

巨噬细胞和中性粒细胞参与了炎症性肠病(inflammatory bowel diseases,IBD)的发生、发展过程。新近研究表明,其他类型细胞如肠道神经胶质细胞(enteric glial cells,EGC)等在此过程中发挥的作用也不可忽视。EGC类似于中枢神经系统(central nervous system,CNS)的星形胶质细胞,具有神经营养支持和神经免疫的属性。本文就EGC在IBD发生、发展过程中的作用及可能机制作一概述。     

参与小胶质细胞活化的膜受体研究进展

<正>在中枢神经系统(CNS),小胶质细胞(MG)的作用越来越受到重视,MG被认为是CNS中天然免疫和适应性免疫的主要调节者〔1〕,MG以静息和活化两种状态存在,静息的MG对CNS起着支持、营养、保护和修复等作用,而活化的MG一方面营养和保护了CNS,另一方面通过释放促炎症细胞因子、自由基、超氧化物阴离子、一氧化氮(NO)、活性氧、前列腺素E2(PGE2)等多种物质,对CNS产生了更多的损伤作用。研究发现活化的     

小胶质细胞及其外泌体在中枢神经退行性疾病中的研究进展

小胶质细胞广泛存在于中枢神经系统, 参与各种病理生理过程, 在阿尔茨海默病、帕金森病、亨廷顿舞蹈症等退行性疾病中发挥重要作用。近几年, 对于小胶质细胞活化产生的外泌体参与各种疾病的病理生理过程的研究备受关注, 但外泌体的作用并未完全明确。本文主要对于小胶质细胞的特点、功能、小胶质细胞源性外泌体的特点和功能及其在中枢神经退行性疾病中的作用进行综述。     

小胶质细胞Toll样受体4信号转导通路与中枢神经系统损伤

中枢神经系统损伤机制复杂,小胶质细胞参与了多种中枢神经系统疾病和损伤过程.Toll样受体4(Toll-like receptor 4,TLR4)可介导小胶质细胞的活化和炎性细胞因子的表达,是小胶质细胞发挥功能的重要受体蛋白之一.文章简要介绍了小胶质细胞TLR4信号通路在中枢神经系统损伤中的作用.     

Editorial Board

Central nervous system (CNS) involvement with diffuse large B‐cell lymphoma (DLBCL) is a relatively uncommon manifestation; with most cases of CNS involvement occuring during relapse after primary therapy. CNS dissemination typically occurs early in the disease course and is most likely present subclinically at the time of diagnosis in many patients who later relapse in the CNS. CNS relapse in these patients is associated with poor outcomes. Based on a CNS relapse rate of 5% in DLBCL and weighing the benefits against the toxicities, universal application of CNS prophylaxis is not justified. The introduction of rituximab has significantly reduced the incidence of CNS relapse in DLBCL. Different studies have employed other agents for CNS prophylaxis, such as intrathecal chemotherapy and high‐dose systemic agents with sufficient CNS penetration. If CNS prophylaxis is to be given, it should be preferably administered during primary chemotherapy. However, there is no strong evidence that supports any single approach for CNS prophylaxis. In this review, we outline different strategies of administering CNS prophylaxis in DLBCL patients reported in literature and discuss their advantages and drawbacks.     

系统性红斑狼疮中枢神经系统病变的诊断及治疗

目的 对系统性红斑狼疮（ＳＬＥ）患中枢神经系统病变（ＣＮＳ）的诊治经验进行总结,方法 对北京协和医院１７１例有ＣＮＳ的ＳＬＥ住院病例进行回顾性分析。结果（１）１７１例发病时ＳＬＥ病程为（２．２１±１．８７）年,１６３例（９５．３％）伴狼疮活动;（２）１５１例行脑脊液检查,异常１３８例（９１．４％）。其中蛋白,压力及白细胞增高分别为１１３．６９及５１例,糖降低仅６例;（３）对有ＣＮＳ的ＳＬＥ,头     

Prognostic factors for clinical outcomes of patients with central nervous system leukemia

Prognostic factors associated with clinical outcomes of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients with central nervous system (CNS) involvement are unknown. We retrospectively studied the characteristics and outcomes of 66 (18 pediatric and 48 adult) patients with CNS leukemia with ALL (n = 41) or AML (n = 25). The median age of patients at diagnosis of CNS leukemia was 30 (range, 1–69) years. Nearly two-third patients had CNS involvement at the initial diagnosis of leukemia. Complete remission of CNS leukemia was attained in 58 (88%) patients, and probability of overall survival at 36 months after the diagnosis of CNS leukemia was 43% for the entire cohort. We identified that achieving remission of systemic leukemia and having CNS leukemia diagnosed and treated before allogeneic transplantation were the factors associated with CNS leukemia remission. Prognostic factors associated with better overall survival in patients with CNS leukemia included pediatric age, diagnosis of CNS leukemia before receiving allogenic transplantation, achieving clearance of systemic or CNS leukemia, receiving no cranial radiation in conjunction with intrathecal chemotherapy (IT), and receiving IT consolidation after achieving remission of CNS leukemia. Our findings show that patients with CNS leukemia are at considerable risk of mortality. Awareness of modifiable prognostic factors such as avoidance of cranial radiation whenever possible and use of IT consolidation can result in improved outcomes in subset of patients with CNS leukemia.     

Diagnosis and pathogenesis of CNS lupus

Summary The central nervous system (CNS) is clinically involved in approximately 40% of all systemic lupus erythematosis (SLE) patients. Minor psychiatric symptoms and abnormalities on neuropsychological testing are being detected with increasing frequency. This review summarizes current thinking concerning the diagnosis and pathogenesis of CNS lupus. The main symptoms of CNS lupus can be diffuse (generalized seizures, psychosis) or focal (stroke, peripheral neuropathies). Neuropsychiatric symptoms often occur in the first year of SLE, but are rarely the presenting symptoms of the disease. In studies on the pathology of CNS lupus, vasculopathy, infarcts and haemorrhages are often observed, whereas vasculitis is rare. Endocardial lesions and mural thrombi have also been reported in 33–50% of CNS lupus patients. In fliagnostic imaging of the CNS, magnetic resonance imaging (MRI) scans often provide evidence for edema or small infarcts, both in focal and diffuse CNS lupus, whereas computerized tomography (CT) scans only show gross abnormalitites. The first reports on position emission tomography (PET) scans in CNS lupus patients show decreased glucose uptake in the brain. The cerebral blood flow decreases during active diffuse and focal CNS lupus. The blood-brain barrier is somewhat more frequently impaired in diffuse CNS lupus. Intrathecal IgG and IgM production is observed in 25–66% of all CNS lupus patient. Various specificities of autoantibodies have been observed in CNS lupus. Of these, anticardiolipin (ACA) antibodies show a well-documented association with focal involvement of the CNS in SLE. These antibodies could cause thrombosis by interfering with the protein C pathway of fibrinolysis. In addition, they are associated with endocardial and valvular heart disease, which is often observed in SLE and which could cause ombolism. The relation between ACA and diffuse CNS lupus is not yet clear. Low-avidity anti-DNA antibodies are also found in CNS lupus, possibly because of their fross-reaction with cardiolipin. Antineuronal antibodies and lymphocytotoxic antibodies have been associated with diffuse CNS lupus and abnormalities on neuropsychological testing. However, the population of these antibodies is rather heterogeneous and it has not been possible to assess a common target antigen. Therefore, it is still obscure whether there is also a second immune-mediated mechanism responsible for the development of the diffuse form of CNS lupus.     

Central nervous system involvement in adult acute lymphoblastic leukemia

Central nervous system (CNS) involvement is identified at the time of diagnosis in less than 10% of adult acute lymphoblastic leukemia (ALL). These patients can attain long-term disease-free survival. CNS disease at presentation does not appear to be an independent poor prognostic factor. Because of the difficulty in treating CNS leukemia, innovative treatments and alternative delivery techniques are needed. The outcome in such patients is a reflection of an aggressive systemic and CNS-directed therapy. However, CNS toxicity represents the dose-limiting side effect of treatment. With effective CNS prophylaxis including intrathecal chemotherapy, high-dose systemic administration of certain agents and cranial irradiation, most adults with ALL without CNS disease at diagnosis may remain free of CNS leukemia. Leukemic relapse remains a major therapeutic problem and CNS involvement at the time of relapse occurs in 1-15% of cases. Adult ALL with CNS recurrence remains of poor prognosis and is generally associated with a systemic relapse.     

NON-HODGKIN'S LYMPHOMA INVOLVING THE CENTRAL NERVOUS SYSTEM

Abstract: :In 44 out of 758 patients (5.8%) with non-Hodgkin's lymphoma presenting between 1971 and 1982, the central nervous system (CNS) was involved. Patients with a diffuse histology had a 7.6% (34/449) incidence of CNS involvement compared to 3.9% (10/257) for patients with nodular lymphoma. In 63% of patients there was evidence of progressive systemic lymphoma at the time of diagnosis of CNS disease and in 23% CNS relapse occurred in clinical remission. Bone marrow was involved in 34% of patients at diagnosis and in 52% at some time prior to the onset of CNS complications. Cerebrospinal fluid cytology was positive in 63% and an elevated protein level was found in 95% of patients. The median length of survival of the 44 patients was only 3.2 months, but patients who responded to treatment of CNS lymphoma survived significantly longer than those who showed no response or progressed on therapy. Complete response to CNS treatment was achieved in five patients, of whom none relapsed in the CNS and two are long-term disease-free survivors. CNS prophylaxis appears justified for patients with lymphoblastic lymphoma, Burkitt's tumour, and diffuse undifferentiated lymphoma, who are at high risk of developing CNS complications. Patients with diffuse histiocytic, and diffuse poorly differentiated lymphocytic, lymphoma who have bone marrow involvement may also benefit from CNS prophylaxis.     

Retrospective study of prognostic factors in non-Hodgkin lymphoma secondarily involving the central nervous system

The aim of this retrospective single-center study was to analyze the clinical characteristics and outcome of non-Hodgkin lymphoma (NHL) patients with central nervous system (CNS) involvement and to identify prognostic factors for survival. We searched our hospital records for NHL patients diagnosed with CNS involvement from 1982 to 2004, and 43 patients were identified. The median age was 63 years (range 23–88) and the median Karnofsky performance status was 55% (range 10–90). Treatment of CNS lymphoma included intrathecal chemotherapy in 33 patients (77%), systemic chemotherapy in 25 (58%), and radiotherapy in 16 (37%). Twenty-six patients showed a CNS response. The median survival after CNS manifestation was 5 months (range 2 days–82.5+months). Nine patients achieved long-term survival. Low lactate dehydrogenase (LDH) at CNS manifestation and a CNS response to therapy were favorable independent prognostic factors for survival in multivariate analysis (p=0.051 and p<0.0005, respectively), whereas a young age at initial diagnosis, initial CNS involvement, an initially normal LDH, and high-dose chemotherapy for CNS involvement were significant in univariate analysis. In conclusion, long-term survival can be achieved in patients with secondary CNS lymphoma. LDH at CNS manifestation and a CNS response to therapy were significantly associated with survival.     

Central nervous system involvement in adult acute lymphoblastic leukemia

Abstract

Central nervous system (CNS) involvement is identified at the time of diagnosis in less than 10% of adult acute lymphoblastic leukemia (ALL). These patients can attain long-term disease-free survival. CNS disease at presentation does not appear to be an independent poor prognostic factor. Because of the difficulty in treating CNS leukemia, innovative treatments and alternative delivery techniques are needed. The outcome in such patients is a reflection of an aggressive systemic and CNS-directed therapy. However, CNS toxicity represents the dose-limiting side effect of treatment. With effective CNS prophylaxis including intrathecal chemotherapy, high-dose systemic administration of certain agents and cranial irradiation, most adults with ALL without CNS disease at diagnosis may remain free of CNS leukemia. Leukemic relapse remains a major therapeutic problem and CNS involvement at the time of relapse occurs in 1–15% of cases. Adult ALL with CNS recurrence remains of poor prognosis and is generally associated with a systemic relapse.     

Quantification of the Limulus polphemus CNS chromatophorotropin.

Assays of the Limulus polyphemus CNS material active as a chromatophorotropin in Uca pugilator (i.e., LUC) revealed LUC presence in larval, immature, and mature CNS, and in the CNS of both sexes of postlarval animals. No sexual difference in LUC levels was demonstrable. Assays of immature and mature CNS demonstrated higher LUC levels/mg CNS in the former, and assays of CNS from specific immature molt cycle stages showed LUC levels/mg CNS to be highest in postmolt and lowest in premolt. A unit of LUC activity was defined. Evidence suggesting that LUC may be a neurosecretory hormone in Limulus is discussed.     

Cerebral imaging by magnetic resonance imaging and single photon emission computed tomography in systemic lupus erythematosus with central nervous system involvement

OBJECTIVE: To assess the significance of magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) abnormalities in patients with systemic lupus erythematosus (SLE). METHODS: Forty-four patients with SLE were retrospectively analysed. Patients were classified into three groups [1 and 2: patients with central nervous system (CNS) manifestations before and after starting high-dose steroid therapy, respectively; 3: patients without CNS manifestations. MRI was performed in all 44 patients and SPECT in 31. RESULTS: Abnormal findings in MRI were found in 19 patients. MRI abnormalities were significantly more frequent in patients with CNS manifestations than in those without [71 vs 17%, odds ratio (OR) 11.9, confidence interval (CI) 2.8-49.9, P=0.0003]. After the initiation of steroid therapy, patients with CNS manifestations also had an increased frequency of abnormal MRI. No correlation was found between SPECT findings and CNS manifestations. However, patients with CNS manifestations after starting steroids showed a markedly increased frequency of abnormal MRI and SPECT compared with those without CNS manifestations (80 vs 7%; OR 56, CI 4.4-719, P=0.0003). The positive predictive value of abnormality in both techniques in developing CNS manifestations after starting steroids was 89%. CONCLUSION: MRI findings correlated with CNS manifestations in SLE. Where there is a high suspicion of CNS involvement, the combination of MRI and SPECT may be useful in predicting CNS manifestations after starting steroid therapy.