Purpose:Auto-immune glial fibrillary acidic protein (GFAP) astrocytopathy is a disease with unclear mechanisms and no diagnostic and treatment guidelines. Epstein-Barr virus (EBV) infection is reportedly involved in glial activities. However, the relationship between GFAP astrocytopathy and EBV infection is not clear. This study reports a case series of auto-immune GFAP astrocytosis with positive cerebrospinal fluid (CSF) EBV DNA, describing its clinical manifestations and treatment experience. Patients and Methods:In the serial case study, we reported six patients diagnosed with GFAP astrocytopathy having intrathecal EBV. Results:The significant signs included headache, fever and urination disorder, ataxia, limb weakness, numbness, consciousness disorder, psychological disorder, and blindness, among others. CSF analysis showed increased pressure, white blood cell count, abnormal biochemical components, positive GFAP antibody, and EBV. The positive results of metagenomic next-generation sequencing (mNGS) and PCR in CSF indicated that there might be active replication of EBV in the CSF of patients. The results of EBV-associated antibodies in blood suggest no evidence of acute primary EBV infection in six patients. Initial single antivirus therapy did not show satisfactory effects, but all patients showed improvement in clinical features and laboratory analysis after immunotherapy. Conclusion:This study indicated that intrathecal EBV activity was closely related to auto-immune GFAP astrocytopathy, of which the mechanism remains to be further studied.

IntroductionMethamphetamine (METH) abuse primarily affects the central nervous system (CNS), leading to CNS damage and contributing to depressive-like behaviors, cognitive impairment, and other neuropsychiatric disorders. Electroacupuncture (EA) has shown promise in treating mental disorders linked to CNS damage, yet the effects of EA on METH-induced depressive-like behaviors and cognitive impairment and it’s underlying therapeutic mechanisms remain largely unclear.MethodsIn this study, a mouse model of METH-induced neuropsychiatric dysfunction was established by administering high-dose METH under elevated ambient temperature. EA was applied at different frequencies to the Zusanli (ST36) acupoint for 7 days post-METH administration.ResultsBehavioral tests revealed that low-frequency EA significantly alleviated depressive-like behaviors and cognitive impairment. Additionally, EA restored blood-brain barrier (BBB) integrity, as evidenced by Western blotting (WB) and Evans blue staining. Neuronal injury was attenuated, as shown by Nissl and hematoxylin and eosin (HE) staining. Further investigations into neuroinflammation revealed that EA suppressed microglial activation in the hippocampus, decreased the expression of IL-6 and TNF-α, and inhibited the NF-κB/NLRP3 signaling pathway.DiscussionThe present study suggested that EA alleviates METH-induced depressive-like behaviors and cognitive impairment by modulating neuroinflammation, particularly through the inhibition of microglial activation and pro-inflammatory cytokine release. EA may represent a promising non-pharmacological strategy for the treatment of METH-associated neuropsychiatric disorders.

目的 探索自我互补腺相关病毒载体介导的人胰岛素样生长因子-1(scAAV9-IGF-1)转导至G93A-SOD1转基因小鼠神经元及其对线粒体的作用.方法 采用肌萎缩侧索硬化(ALS)的转基因G93A-SOD1及野生型(wild type-SOD1,WT-SOD1)小鼠为动物模型,在60 d龄时,同窝阳性G93A-SOD1转基因雌性小鼠采用随机的方法分配到治疗组肌肉注射scAAV9-IGF-1,载体对照组肌肉注射AAV9-GFP,及同年龄WT-SOD1作为阴性对照.在肌肉注射后约40～50 d时,通过免疫组化染色观察IGF-1在腰髓神经元中的表达,利用免疫荧光染色观测腰髓组织绿色荧光蛋白(GFP)的表达特点;用透射电镜观察腰髓前角运动神经元中线粒体的形态学变化;提取小鼠脊髓细胞进行流式细胞学分析线粒体膜电位变化;腓肠肌进行免疫组化染色观察线粒体变化.结果 免疫荧光染色观测腰髓组织GFP的表达主要在神经元,免疫组化染色观察IGF-1表达于腰髓神经元中.透射电镜观察GFP组线粒体存在嵴消失、空泡化、胞浆水肿、核染色质疏松,而IGF-1组线粒体形态与WT组相似,为长椭圆形,未见嵴消失、空泡化等现象.流式细胞学分析IGF-1组降低了线粒体膜电位的除极.在GFP对照组中腓肠肌的苏木精-伊红染色中观察到严重萎缩的肌纤维,而在IGF-1处理的小鼠中肌肉萎缩减少.Gomori染色显示IGF-1处理后,肌肉细胞的线粒体染色增多,同WT组相当.结论 scAAV9-IGF-1可以保护G93A-SOD1转基因小鼠模型中的线粒体,其通过减少线粒体膜电位除极,改善线粒体形态,减少腓肠肌肌肉萎缩,从而产生保护线粒体的作用.

Abstract Background Neurocysticercosis (NCC) presents a wide range of complex clinical manifestations and various complications, which depend on factors such as the number and size of cysticerci, developmental stage, brain location, and immune response.This study reports the diagnosis, treatment, and follow-up of a patient with neurocysticercosis complicated with hydrocephalus for up to two years. Case presentation: This study describes the clinical, radiological, and immunological features of a patient who initially presented with recurrent episodes of unconsciousness over five months. Next-generation sequencing (NGS) was employed to identify the pathogen, and DNA from the pork tapeworm was detected in the patient's cerebrospinal fluid. Insecticidal treatment with praziquantel was administered, and upon readmission, secondary hypothyroidism was diagnosed, indicating the presence of hypopituitarism. Hormone treatment and thyroid hormone supplementation were initiated, resolving the patient's clinical symptoms and restoring thyroid function. Conclusions The manifestations of cerebral cysticercosis are diverse, underscoring the importance of accurate diagnosis and proactive intervention. Given the intricate and varied nature of these complications, extended follow-up emerges as a critical component. Such prolonged monitoring plays a pivotal role in determining the prognosis and enhancing the overall quality of life for affected individuals.

目的 探索莱菔硫烷(SFN)对培养的Nrf2+/+、Nrf2-/-原代星形胶质细胞Ⅱ相酶的诱导作用.方法 取经基因鉴定的Nrf2+/+、Nrf2-/-新生乳鼠,取出大脑皮质分离培养原代星形胶质细胞,并进行纯化与鉴定.将细胞分为Nrf2+/+和Nrf2-/-组,每组又分为溶剂对照组和SFN药物干预组.通过给予不同浓度的SFN干预Nrf2+/+组细胞,测定Ⅱ相酶的表达来选择最佳给药浓度.然后分别给予Nrf2+/+、Nrf2-/-组DMSO和最适浓度的SFN,通过Western blot测定Ⅱ相酶的表达.结果 不同浓度SFN干预Nrf2+/+星形胶质细胞显示,10μmol·L-1对Ⅱ相酶Gclm、Nqo1、Ho1蛋白表达的诱导作用最强,为最佳给药浓度.Nrf2+/+和Nrf2-/-细胞分别给予10μmol·L-1 SFN处理后,Ho1均能明显上调.Nqo1和Gclm只在Nrf2+/+细胞中明显上调,在Nrf2-/-细胞中不上调.而对于Gss和Gclc,给药后Nrf2+/+和Nrf2-/-细胞两种酶表达均无明显变化.结论 SFN对原代培养的星形胶质细胞Ho1的诱导不完全依赖于核转录因子Nrf2;对Nqo1、Gclm的诱导很大程度上依赖于转录因子Nrf2;对Gss和Gclc的表达无明显诱导作用.

目的 利美尼定对家族性肌萎缩侧索硬化症(ALS)相关突变蛋白质SOD1G93A的作用机制.方法 用瞬时转染的方法在运动神经元样细胞系NSC-34中过表达WTSOD1,与家族型ALS相关的SOD1G93A突变蛋白,再给予自噬通路的特异性诱导剂和阻断剂,通过Western blot蛋白印迹法检测突变SOD1、自噬标记物的蛋白质表达水平.结果 自噬诱导剂trehalose可以使SOD1G93A蛋白质表达水平明显减少.在自噬阻断剂3-甲基腺嘌呤(3-MA)的干预下,SOD1G93A蛋白质表达水平明显升高.l0uM利美尼定能够明显降低G93A SOD1的表达,但对WT SOD1的表达水平无明显影响.结论 SOD1G93A主要经由自噬途径降解,利美尼定能够明显促进G93A SOD1的降解,但对WT SOD1的蛋白质表达水平无明显促进作用.

The role of oligodendrocyte lineage cells, the largest glial population in the adult central nervous system (CNS), in the pathogenesis of Alzheimer's disease (AD) remains elusive. Here, we developed a culture method for adult oligodendrocyte progenitor cells (aOPCs). Fibroblast growth factor 2 (FGF2) promotes survival and proliferation of NG2+ aOPCs in a serum-free defined medium; a subpopulation (~5%) of plexin-B3+ aOPCs was also found. FGF2 withdrawal decreased NG2+, but increased plexin-B3+ aOPCs and Aβ1-42 secretion. Plexin-B3+ aOPCs were distributed throughout the adult rat brain, although less densely than NG2+ aOPCs. Spreading depolarization induced delayed cortical plexin-B3+ aOPC gliosis in the ipsilateral remote cortex. Furthermore, extracellular Aβ1-42 accumulation was occasionally found around plexin-B3+ aOPCs near the lesions. In AD brains, virtually all cortical SPs were immunostained for plexin-B3, and plexin-B3 levels increased significantly in the Sarkosyl-soluble fractions. These findings suggest that plexin-B3+ aOPCs may play essential roles in AD pathogenesis, as natural Aβ-secreting cells.

水通道蛋白4(AQP4)是维持中枢神经系统正常跨膜水转运、血-脑屏障完整性和中枢神经系统内环境稳定的水通道蛋白,其特异性自身抗体AQP4抗体(即NMO-IgG)是视神经脊髓炎谱系疾病(NMOSD)的特异性生物学标志物,但部分临床及影像学表现符合NMOSD的患者血清中未能检测到该抗体,因此2015年NMOSD诊断标准国际共识根据AQP4抗体的表达状态,将其分为AQP4抗体阳性和AQP4抗体阴性两部分.此后许多学者发现二者在临床表现、影像学、脑脊液及预后等方面存在一定的差异,更深入的研究发现其致病机制可能不同.本文拟就近年来各研究关于AQP4抗体阳性与阴性NMOSD患者在以上方面是否存在差异进行综述.

视神经脊髓炎(neuromyelitis optica,NMO)是一种主要累及视神经和脊髓的中枢神经系统自身免疫性炎性脱髓鞘疾病.临床中有一组不能满足NMO的诊断标准但与其有着相似发病机制和临床特征的疾病,因此,Wingerchuk等在2007年首次提出视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorders,NMOSD)的概念.国际视神经脊髓炎诊断小组(the international panel for NMO diagnosis,IPND)于2015年对Wingerchuk诊断标准进行修订提出新的诊断标准,并将NMO纳入NMOSD中.新标准提出NMOSD的6个核心特征包括:视神经炎、急性脊髓炎、最后区综合征、急性脑干综合征、发作性嗜睡或急性间脑症状伴MRI显示的NMOSD典型的间脑病灶,以及大脑综合征伴 NMOSD典型的大脑病灶.最后区综合征与视神经炎和急性脊髓炎是NMOSD最常见的3种临床表现,在AQP4抗体阴性或无法检测的NMOSD的诊断中,其价值等同于视神经炎和急性脊髓炎.本文旨在结合文献回顾性分析以最后区综合征(不明原因的呃逆、恶心或呕吐)起病的6例NMOSD患者的临床资料特点,以期为临床诊疗提供参考.

自噬是一种基础的分解代谢过程，与细胞的存活、分化、发育和内环境稳态的维持密切相关。近年来研究发现，自噬在清除神经变性疾病相关的错折叠蛋白质和易聚集蛋白质方面起着重要作用。本文就自噬及其在神经变性疾病领域的研究做一综述。

目的 探索肌萎缩侧索硬化症(ALS)相关TDP-43的降解机制.方法 用瞬时转染的方法在运动神经元样细胞系NSC-34中过表达野生型(role of wild-type,WT) WT TDP-43,与家族型ALS相关的Q331K TDP-43、M337V TDP-43突变蛋白、TDP-43的两种C末端片段TDP-25和TDP-35,再给予自噬、蛋白酶体通路的特异性诱导剂和阻断剂,通过蛋白印迹方法检测5种TDP-43以及自噬标记物LC3-Ⅱ的表达水平.结果 在自噬诱导剂作用下,各组LC3-Ⅱ的表达升高,同时两种突变TDP-43及其C末端片段的表达明显减少,在自噬通路和蛋白酶体阻断剂作用下突变TDP-43及其C末端片段表达水平明显增多,而WT TDP-43的蛋白表达水平仅在蛋白酶体阻断剂作用时增多.结论 WT TDP-43主要经由蛋白酶体途径降解,Q331K TDP-43、M337V TDP-43及其C末端片段经由蛋白酶体途径和自噬两种途径降解.

The relationship between depression and Alzheimer's disease (AD) has always been relevant and controversial. Here, we briefly review epidemiological and biological studies that have investigated these disorders and then introduce our recent research about postmortem brains from patients with major depressive disorder (MDD). Our novel methodological approaches have revealed thatMDDmay be associated with an unknown type of myelin/ myelination abnormalities in the frontopolar cortex. Based mainly on our findings, as well as on neuropathological observations by Braak and Braak (Acta Neuropathol 9, 197-201, 1996), we discuss the possible existence of an as yet unknown common mechanism linking the pathophysiologies underlying both depression and AD.

BACKGROUND:In vivo studies have shown that the high concentration of glucocorticoids can inhibit the proliferation of rat endogenous neural precursor cel s. Neuron-glia antigen 2 proteoglycan-positive neural progenitor cel s are the largest proliferating cel population in the mature central nervous system, which are pluripotent cel s. OBJECTIVE:To investigate the effects of glucocorticoid on the survival and proliferation of the neuron-glia antigen 2 proteoglycan-positive neural progenitor cel s from in vitro cultured adult rat hippocampus. METHODS:Neuron-glia antigen 2 proteoglycan-positive neural progenitor cel s were primary cultured and sub-cultured. The passage 1 cel s were treated with dexamethasone with the concentrations of 0, 0.1, 1, 10 and 100μmol for 48 hours, and then the cel activities were determined by lactate dehydrogenase assay, the apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay, and the proliferation of the cel s was identified by 5'-bromodeoxyuridine incorporation method. RESULTS AND CONCLUSION:Dexamethasone with the concentrations of 1, 10 and 100μmol could decrease the number of the neuron-glia antigen 2 proteoglycan-positive neural progenitor cel s, increase the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling positive cel s, and significantly reduce the number of BrdU positive cel s. High concentration of glucocorticoid can decrease the number of the neuron-glia antigen 2 proteoglycan-positive neural progenitor cel s by inhibiting the proliferation and inducing the apoptosis.

BACKGROUND: Cerebrolysin can relieve the symptoms of many nervous system diseases, but the precise mechanism remains poorly understood. Cerebrolysin has been shown to promote neurogensis by in vivo and in vitro experiments. OBJECTIVE: To investigate the effects of cerebrolysin on the proliferation and differentiation of cultured neuroglia antigen 2-positive neural progenitor cells. METHODS: Neuroglia antigen 2 cells from the hippocampus of the adult rats were primary cultured and sub-cultured. Cel characteristics were identified by immunofluorescence staining. Cel viability was determined by lactate dehydrogenase assay. Cel apoptosis was detected by TUNEL method. The newly generated cells were identified by BrdU incorporation. RESULTS AND CONCLUSION: Cerebrolysin significantly decreased the number of TUNEL-positive cells and significantly increased the number of neuroglia antigen 2-positive cells and the expression level of microtubule-associated protein 2a+2b, synapsin I, γ-aminobutyric acid and vesicularγ-aminobutyric acid transporter in neuroglia antigen 2-positive cells. These findings suggest that cerebrolysin can inhibit neuroglia antigen 2-positive cel apoptosis, promote neuroglia antigen 2-positive cel proliferation and differentiation into neurons (especial y GABAergic inhibitory interneurons).

Recent studies suggest that schizophrenia (SCH) and bipolar disorder (BPD) may share a similar etiopathology. However, their precise neuropathological natures have rarely been characterized in a comprehensive and quantitative fashion. We have recently developed a rapid, quantitative cell-counting method for frozen unfixed postmortem brains using a flow cytometer. In the present study, we not only counted stained nuclei, but also measured their sizes in the gray matter of frontopolar cortices (FPCs) and inferior temporal cortices (ITCs) from patients with SCH or BPD, as well as in that from normal controls. In terms of NeuN(+) neuronal nuclei size, particularly in the reduced densities of small NeuN(+) nuclei, we found abnormal distributions present in the ITC gray matter of both patient groups. These same abnormalities were also found in the FPCs of SCH patients, whereas in the FPCs of BPD patients, a reduction in oligodendrocyte lineage (olig2(+)) cells was much more common. Surprisingly, in the SCH FPC, normal left-greater-than-right asymmetry in neural nuclei densities was almost completely reversed. In the BPD FPC, this asymmetry, though not obvious, differed significantly from that in the SCH FPC. These findings indicate that while similar neuropathological abnormalities are shared by patients with SCH or BPD, differences also exist, mainly in the FPC, which may at least partially explain the differences observed in many aspects in these disorders.

组蛋白去乙酰化酶( HDACs)的主要功能是去除组蛋白N-末端的赖氨酸残基乙酰基部分,使染色质变得致密,从而抑制基因转录.但是有些HDACs,例如HDAC6,也能够影响细胞内非组蛋白的功能.研究显示,HDAC6参与细胞内自噬的降解过程[1],自噬是包括人在内的真核生物共有的一种高度进化保守机制,调节细胞质长寿命蛋白、损伤的细胞器以及异常蛋白聚集物的更新和重复利用.研究HDAC6与自噬的关系将为神经变性疾病的治疗提供新的线索.

In patients with amyotrophic lateral sclerosis (ALS), various mutations were identified in TAR DNA-binding protein-43 (TDP-43). In the present study, we found that mutant TDP-43 inhibited the neurite outgrowth. Subsequently, we tested the effect of MG132 on the mutant TDP-43 cell lines. Non-toxic doses of MG132 promoted neurite extension and decreased the level of thiobarbituric acid-reactive substances (TBARS). Heme oxygenase-1 (HO-1) known as antioxidase was restored by MG132. Conversely, Zinc protoporphyrin IX (ZnPP IX), which is an inhibitor of heme oxygenase, inhibited neurite outgrowth induced by MG132. It was well known that HO-1 was regulated by nuclear factor E2-related factor 2 (Nrf2). However, MG132 increased the expression of HO-1 independent of the Nrf2 pathway.

Objective To explore the mechanism of Cerebrolysin(CL)improving the cognitive function in Alzheimer's disease by studing the effects of CL on proliferation and differentiation of neural progenitor cells(NPCs)in vitro.Methods NPCs primary culture was done from different regions of the adult rat brain.The characteristics of the cells were identified by immunofluorescence stain,the cell activities were determined by lactate dehydrogenase(LDH)assay,and the expression level of proteins were identified by western blot.Results CL increased the number and the expression level of MAP2a/b and Synapsin I of NPCs significantly.Conclusion CL promotes proliferation and neuronal differentiation of NPCs,it may be one of the mechanisms that how CL improves the cognitive function in Alzheimer's disease.

Objective To investigate the effects of Cerebrolysin(CL) on the proliferation of the NG2 proteoglycan-positive neural progenitor cells (NG2 cells).Methods NG2 cell primary culture was done from adult rat hippocampus according to the reference.The characteristics of the cells were identified by immunofluorescence stain,the cell activities were determined by Lactate dehydrogenase (LDH) assay,apoptosis was detected by TUNEL method,and the new born cells were identified by BrdU.Results CL increased the number of the NG2 cells,and decreased the number of TUNEL positive cells significantly,but had little effect on the BrdU positive cells.Conclusion CL increases the proliferation of NG2 cells by inhibiting the apoptosis.

Objective To investigate the effects of amino acid on the proliferation of the neuron-glia anti-gen 2(NG2) proteoglycan-positive neural progenitor cells (NG2 cells). Methods NG2 cells were separated from different regions of the adult rats' central nervous system (CNS), and treated with different amino acid in 0.1-0.5mmol for 72 hours, the cell activities were determined by lactate dehydrogenase (LDH) assay. Results 0.3mmol glutamic acid and aspartic acid increased the number of the NG2 cells from different brain regions(p0.001). Conclusion Excitatory amino acids(EAAs) in high concentration increase the proliferation of NG2 cells.