Acrylamide exposure impairs blood-cerebrospinal fluid barrier function

Previous studies show that chronic acrylamide exposure leads to central and peripheral neu- ropathy. However, the underlying mechanisms remained unclear. In this study, we examined the permeability of the blood-cerebrospinal fluid barrier, and its ability to secrete transthyretin and transport leptin of rats exposed to acrylamide for 7, 14, 21 or 28 days. Transthyretin levels in cerebrospinal fluid began to decline on day 7 after acrylamide exposure. The sodium fluorescein level in cerebrospinal fluid was increased on day 14 after exposure. Evans blue concentration in cerebrospinal fluid was increased and the cerebrospinal fluid/serum leptin ratio was decreased on days 21 and 28 after exposure. In comparison, the cerebrospinal fluid/serum albumin ratio was increased on day 28 after exposure. Our findings show that acrylamide exposure damages the blood-cerebrospinal fluid barrier and impairs secretory and transport functions. These changes may underlie acrylamide-induced neurotoxicity.

Lessons from glaucoma: rethinking the fluid-brain barriers in common neurodegenerative disorders

Glaucoma has been recently characterized as a member of the group of anoikis-related diseases. Anoikis, a form of apoptosis, can be triggered by the unfastening of adherent junctions present in astrocytes. In those areas of the central nervous system in which the soma of the neurons or their axons and dendrites are metabolically dependent on the activity of astrocytes, a derangement of the lactate shuttle caused by a separation between the plasma membranes of neurons and astrocytes would result in metabolic impairment of the neurons themselves. In glaucoma, the triggering event has been attributed to the posterior deviation of aqueous humor towards the astrocyte-rich prelaminar tissue of the optic nerve head. The mean calcium content in the aqueous is able to interfere with calcium-dependent adherent junctions and induce anoikis of the astrocytes. As the cerebrospinal fluid has a similar base calcium concentration, a shunt of cerebrospinal fluid through the cerebral parenchyma would be able to interfere in the astrocytic architecture with dire consequences to the metabolically dependent neurons. Here the similitude between glaucoma,amyotrophic lateral sclerosis and Alzheimer's disease are discussed and the concept of the break in the fluid-brain barrier, as an event separated from the blood-brain barrier, is stressed.

Alzheimer's disease with sleep insufficiency:a cross-sectional study on correlations among clinical characteristics,orexin,its receptors,and the bloodbrain barrier

Previous studies have shown that reduced sleep duration,sleep fragmentation,and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling.At the same time,blood-brain barrier disruption is considered an early biomarker of Alzheimer's disease.However,currently no report has examined how changes in orexin signaling relate to changes in the blood-brain barrier of patients who have Alzheimer's disease with sleep insufficiency.This cross-sectional study included 50 patients with Alzheimer's disease who received treatment in 2019 at Beijing Tiantan Hospital.Patients were divided into two groups:those with insufficient sleep(sleep duration≤6 hours,n=19,age 61.58±8.54 years,10 men)and those with normal sleep durations(sleep duration>6 hours,n=31,age 63.19±10.09 years,18 men).Demographic variables were collected to evaluate cognitive function,neuropsychiatric symptoms,and activities of daily living.The levels of orexin,its receptor proteins,and several blood-brain barrier factors were measured in cerebrospinal fluid.Sleep insufficiency was associated with impaired overall cognitive function that spanned multiple cognitive domains.Furthermore,levels of orexin and its receptors were upregulated in the cerebrospinal fluid,and the blood–brain barrier was destroyed.Both these events precipitated each other and accelerated the progression of Alzheimer's disease.These findings describe the clinical characteristics and potential mechanism underlying Alzheimer's disease accompanied by sleep deprivation.Inhibiting the upregulation of elements within the orexin system or preventing the breakdown of the blood-brain barrier could thus be targets for treating Alzheimer's disease.

脑干带状高信号的软脑膜转移临床特征分析

目的:分析脑干带状高信号的软脑膜转移病例的临床特征。方法:收集海南医学院第一附属医院及检索知网、万方、维普、PubMed、Web of Science等数据库中报道磁共振表现为脑干带状高信号的患者,收集并整理纳入患者的既往病史、症状、体征、基因检查结果、脑脊液表现、治疗及预后等。结果:共纳入28例患者,其中26例有肺腺癌病史,2例发现肺部占位性改变,磁共振均表现为T2‐FLAIR上脑干腹侧呈带状高信号,两侧对称,可延伸至小脑脚,DWI呈高信号,ADC呈低信号,T1加权成像为长T1信号,T2加权成像为长T2信号,增强扫描未见强化。结论:识别肺癌继发软脑膜转移很重要,T2‐FLAIR和DWI上脑干无强化带状高信号很可能是非小细胞肺癌继发软脑膜转移的特征性表现。

贝伐珠单抗抑制大鼠创伤性脑损伤半暗带区BCFB破坏和减轻炎症损伤的机制研究

目的评价贝伐珠单抗(BV)对创伤性脑损伤(TBI)大鼠半暗带区恢复血-脑脊液屏障(BCFB)完整性和减轻炎症损伤的效果,以及NF-κB/MMP-9途径在实验性TBI中的潜在作用。方法大鼠被随机分成创伤组(TBI组)、创伤后应用BV组(药物干预组,TBI+BV组)、假手术组(Sham组)。采用改进的菲尼自由落体法建立大鼠TBI模型,然后用BV抑制TBI中血管内皮生长因子(VEGF)的表达。通过蛋白印迹(Western blot)和免疫组化检测VEGF在各组大鼠中的表达,采用改良神经功能评分(mNSS)、伊文思蓝染色、脑组织含水量、酶联免疫吸附试验(ELISA)和Western blot研究了VEGF的抑制对炎症反应、BCFB完整性以及神经功能恢复的影响。结果研究发现TBI诱导损伤半暗带区VEGF升高,并导致紧密连接蛋白减少,破坏BCFB完整性和介导炎症损伤。与Sham组相比,TBI组及TBI+BV组mNSS评分明显升高,BCFB完整性被显著破坏(脑水肿程度增加和紧密连接蛋白下调),炎症因子白细胞介素-6(IL-6)、白细胞介素-10(IL-10)和转化生长因子β(TGF-β)明显升高。与TBI组相比,TBI+BV组NSS评分显著降低(P<0.05)、紧密连接蛋白显著升高(P<0.05)、脑组织含水量明显改善(P<0.05)、促炎因子IL-6显著下降,抗炎因子IL-10和TNF-β显著升高(P<0.05),Western blot分析表明,BV显著抑制NF-κB/MMP-9通路激活。结论BV通过恢复BCFB完整性、调节炎性因子表达降低炎症损伤、以及抑制NF-κB/MMP-9通路激活抵消TBI后神经损伤,对大鼠TBI有良好的治疗效果。

α-Synuclein pathology from the body to the brain:so many seeds so close to the central soil

α-Synuclein is a protein that mainly exists in the presynaptic terminals.Abnormal folding and accumulation of α-synuclein are found in several neurodegenerative diseases,including Parkinson’s disease.Aggregated and highly phospho rylated a-synuclein constitutes the main component of Lewy bodies in the brain,the pathological hallmark of Parkinson s disease.For decades,much attention has been focused on the accumulation of α-synuclein in the brain parenchyma rather than considering Parkinson s disease as a systemic disease.Recent evidence demonstrates that,at least in some patients,the initial α-synuclein pathology originates in the peripheral organs and spreads to the brain.Injection of α-synuclein preformed fibrils into the gastrointestinal tra ct trigge rs the gutto-brain propagation of α-synuclein pathology.However,whether α-synuclein pathology can occur spontaneously in peripheral organs independent of exogenous α-synuclein preformed fibrils or pathological α-synuclein leakage from the central nervous system remains under investigation.In this review,we aimed to summarize the role of peripheral α-synuclein pathology in the pathogenesis of Parkinson’s disease.We also discuss the pathways by which α-synuclein pathology spreads from the body to the brain.

Analysis of clinical characteristics of leptomeningeal metastasis with band-like high signal in the brainstem

Objective:The aim was to analyse the clinical features of leptomeningeal metastasis with banded high signal in the brainstem.Methods:In this paper,we report two cases of lung adenocarcinoma with soft meningeal metastasis,collected from the First Affiliated Hospital of Hainan Medical College,and searched the databases of CNKI,Wanfang,VIP,PubMed,Web of Science,and other databases which reported the MRI manifestation of"brainstem bandlike high signal",and collected the patients'past medical history,symptoms,signs,genetic findings,cerebrospinal fluid manifestation,treatment,and prognosis.Result:A total of 28 patients were included,of whom 26 had a history of lung adenocarcinoma and 2 were found to have occupational changes in the lungs.Magnetic resonance imaging(MRI)showed a band-like high signal in the ventral part of the brainstem on T2-FLAIR,symmetrical on both sides,which could extend to the cerebellar peduncles,with high signals on diffusion-weighted imaging(DWI),low signals on apparent diffusion coefficient(ADC),and long T1 signals on T1-weighted imaging,long T2 signals on T2 weighted imaging,and no long T2 signals on enhancement scan.T1-weighted imaging was a long T1 signal,T2-weighted imaging was a long T2 signal,and no enhancement was seen on enhanced scanning.Conclusion:It is important to recognize leptomeningeal metastasis of lung cancer,and the non-enhancing band of high signal in the brainstem on T2-FLAIR and DWI is likely to be the characteristic manifestation of leptomeningeal metastasis of non-small cell lung cancer.

基于精气血津液理论的皮肤屏障损伤与修复

皮肤作为人体固有免疫系统的重要组成部分,其屏障功能发挥着至关重要的保护作用。多种皮肤病的发病与皮损屏障功能的损伤相关,皮肤屏障的修复却始终依赖于持续性外源物质的补充。中医自古有皮肤腠理卫外功能的理论,气血津液体系的正常运转维持了皮肤屏障功能的稳态,其紊乱的相关机制是多种皮肤病发病的关键病机。中医传统理论和现代生理学以人体作为共同的认知对象,为人类健康谋福祉,二者一体两面,殊途同归。白彦萍教授作为岐黄学者,在继承前人经验的基础上,总结多年的临床经验,结合皮肤屏障功能“砖墙结构”,提出以精和津液分别作为“砖块”和“灰浆”构成皮肤屏障的基本结构,血为皮肤屏障提供营养供给和排出代谢废物,气发挥主要的防御功能,精气血津液共同维持皮肤屏障功能的正常运转,形成“以精和津液为基,以血为养,以气为用”的皮肤屏障功能理论模型,并初步阐释其联络内外导致皮肤病伴随症状的理论依据,为皮肤病精气血津液层面的诊疗提供了更加详细的理论基础。

基于热流固的热障涂层整体叶盘振动特性研究

为了研究复杂载荷对整体叶盘振动特性的影响,基于热流固耦合方法对热障涂层整体叶盘振动特性进行研究。简化整体叶盘模型,对叶片表面涂敷热障涂层并建立整体叶盘的流场模型;在Fluent中采用热流固耦合方法对整体叶盘的表面进行气动载荷和温度载荷的模拟;最后,采用预应力模态分析法分别对不同工况下整体叶盘的振动特性进行分析。结果表明:考虑离心载荷对整体叶盘的固有频率影响最大,温度的影响最小;对比不同工况下,考虑温度载荷对整体叶盘的共振点个数无影响,气动载荷增加整体叶盘的共振点个数。

道路声屏障对交通空气污染物扩散的影响

道路声屏障是缓解快速路噪声污染的主要物理措施,同时能一定程度上影响交通空气污染物的扩散。为探索道路声屏障对交通空气污染物扩散的影响,基于流体动力学理论,运用Fluent进行污染物扩散仿真模拟。本研究考虑道路声屏障高度变化和快速路外污染源距离,对比不同工况下污染物扩散分布情况,最终得出道路声屏障对空气污染物的影响。结果显示,道路声屏障能有效降低快速路下风处附近污染物浓度,且对路外上风处污染物的扩散具有阻挡作用,5 m声屏障工况下污染物浓度降低超过30%。此外,污染物浓度随着快速路外污染源距离的增加而降低,在无声屏障时,外部污染源距离400 m相较于距离300 m和200 m时,迎风侧80 m范围内的污染物浓度分别下降了15%和38%,但声屏障对这一影响存在抑制作用,有5 m声屏障时,污染物浓度分别降低13%和25%。声屏障既降低区域暴露水平又一定程度上阻碍污染物扩散,因此在考虑运用声屏障或者相关物理结构改造措施来缓解交通空气污染时,应当综合考虑其利弊。

大气压He/CF4脉冲介质阻挡放电参数效应研究

He/CF4等离子体在表面改性领域得到了广泛的应用。采用一维流体模型对大气压He/CF4脉冲介质阻挡放电等离子体进行了数值模拟,通过计算分析等离子体在放电过程中各粒子的浓度以及各反应的贡献率,研究了不同放电参数(放电间隙、介质板厚度和相对介电常数)对等离子体的影响。结果表明:电子碰撞反应在各活性粒子的生成中均起到了重要作用;不同放电参数对各粒子浓度和产物粒子的反应贡献率产生不同的影响。

How Do Water Filled Traffic Barriers Shake a Suspension Bridge?

The present study stems from the realization that the general problem relating to the analysis of wind-induced vibrations in suspension bridges still requires significant attention.Sidewalk railings,overhaul tracks,and deflectors are known to largely affect such dynamics.Here,the influence of a row of water-filled traffic barriers on the response of a sample suspension bridge is investigated numerically.It is shown that the existence of water barriers causes flow separation and non-negligible vortices with respect to the condition with no water barriers.The vortex shedding frequency at the far end is around 41.30 Hz,relatively close to the real vibration frequency.It is also shown how different incoming angles of attack can change the flow field around the bridge cross-section and the vortex detachment frequency.

Numerical Study of Fluid Dynamics and Heat Transfer Induced by Plasma Discharges

A numerical investigation is conducted to explore the evolution of a plasma discharge and its interaction with the fluid flow based on a self-consistent fluid model which couples the discharge dynamics with the fluid dynamics.The effects of the applied voltage on the distribution of velocity and temperature in initially static air are parainetrically studied.Furthermore,the spatial structure of plasma discharge and the resulting force contours in streamwise and normal directions are discussed in detail.The result shows that the plasma actuator produces a net force that should always be directed away from the exposed electrode,which results in an ionic wind pushing particles into a jet downstream of the actuator.When the energy added by the plasma is taken into account,the ambient air temperature is increased slightly around the electrode,but the velocity is almost not affected.Therefore it is unlikely that the induced flow is buoyancy driven.For the operating voltages considered in this paper,the maximum induced velocity is found to follow a power law,i.e.,it is proportional to the applied voltage to the 3.5 power.This promises an efficient application in the flow control with plasma actuators.

MASS TRANSPORT IN SOLID TUMORS (Ⅰ)──FLUID DYNAMICS

A three-porous-medium model for transvascular exchange and extravascular transport of fluid and macromolecules in a spherical solid tumor is developed. The microvasculature , lymphatics, and tissue space are each treated as a porous medium with the flow of blood. lymph, and interstitial fluid obeying Darcy's law and Starling 's assumption. In this part, the role of interstitial pressure and fluid convection are studited. The analytical soiutions are obtained for foe isolated tumor and the normal-tissue-surrounded tumor respectively. The calculated interstitial pressure profue are consistent with the experimental observation that the elevated interstitial pressure is a major barrier in the penetration of macromolecular drug into tumors. The factors which may reduce the interstitial pressure are analyzed in details.

The embryonic blood–CSF barrier has molecular elements for specific glucose transport and for the general transport of molecules via transcellular routes

In vertebrates, early brain development takes place at the expanded anterior end of the neural tube, which is filled with embryonic cerebrospinal fluid (E-CSF). We have recently identified a transient blood–CSF barrier that forms between embryonic days E3 and E4 in chick embryos and that is responsible for the transport of proteins and control of E-CSF homeostasis, including osmolarity. Here we examined the presence of glucose transporter GLUT-1 as well the presence of caveolae-structural protein Caveolin1 (CAV-1) in the embryonic blood-CSF barrier which may be involved in the transport of glucose and of proteins, water and ions respectively across the neuroectoderm. In this paper we demonstrate the presence of GLUT-1 and CAV-1 in endothelial cells of blood vessels as well as in adjacent neuroectodermal cells, located in the embryonic blood–CSF barrier. In blood vessels, these proteins were detected as early as E4 in chick embryos and E12.7 in rat embryos, i.e. the point at which the embryonic blood–CSF barrier acquires this function. In the neuroectoderm of the embryonic blood-CSF barrier, GLUT-1 was also detected at E4 and E12.7 respectively, and CAV-1 was detected shortly thereafter in both experimental models. These experiments contribute to delineating the extent to which the blood–CSF embryonic barrier controls E-CSF composition and homeostasis during early stages of brain development in avians and mammals. Our results suggest the regulation of glucose transport to the E-CSF by means of GLUT-1 and also suggest a mechanism by which proteins are transported via transcellular routes across the neuroectoderm, thus reinforcing the crucial role of E-CSF in brain development.

Experimental and simulated investigation of microdischarge characteristics in a pin-to-pin dielectric barrier discharge(DBD)reactor

Both experimental and simulated studies of microdischarge(MD)are carried out in a dielectric barrier discharge with a pin-to-pin gap of 3.5 mm,ignited by a sinusoidal voltage with a peak voltage of 10 kV and a driving frequency of 5 kHz.Statistical results have shown that the probability of the single current pulse in the positive half-period(HP)reaches 73.6%under these conditions.Experimental results show that great luminous intensity is concentrated on the dielectric surface and the tip of the metal electrode.A 1D plasma fluid model is implemented by coupling the species continuity equations,electron energy density equations,Poisson equation,and Helmholtz equations to analyze the MD dynamics on the microscale.The simulated results are in good qualitative agreement with the experimental results.The simulated results show that the MD dynamics can be divided into three phases:the Townsend phase,the streamer propagation phase,and the discharge decay phase.During the streamer propagation phase,the electric field and electron density increase with the streamer propagation from the anode to the cathode,and their maximal values reach 625.48 Td and 2.31×10^(19)m^(-3),as well as 790.13 Td and 3.58×10^(19)m^(-3)in the positive and negative HP,respectively.Furthermore,a transient glow-like discharge is detected around the anode during the same period of streamer propagation.The formation of transient glow-like discharge is attributed to electrons drifting back to the anode,which is driven by the residual voltage in the air gap.

利多卡因通过HMGB1/RAGE信号改善缺血性卒中大鼠血-脑脊液屏障通透性研究

目的探讨利多卡因对缺血性卒中模型大鼠血-脑脊液屏障(BCFB)的影响及其机制研究.方法100只雄性健康的SD大鼠,随机分为假手术组(Sham),缺血性卒中组(MCAO),利多卡因低、中、高剂量组(Lidoc-L,M,H,1 mg·kg^(-1),5 mg·kg^(-1),10 mg·kg^(-1)).采用Longa线栓法构建中动脉缺血(middle cerebral artery occlusion,MCAO)模型,静脉注射不同剂量的利多卡因,2 h后拔出线栓恢复缺血区血流灌注.24h后,参考Longa-Zea标准进行神经功能评分.将大鼠处死,取全脑组织分别开展脑梗死区域染色,BCFB通透性检测,脑水肿程度检测,取缺血侧脑组织分别进行mRNA与蛋白表达检测.结果与Sham组相比,MCAO组大鼠神经功能评分、脑梗死体积、透过BCFB的伊文思蓝含量与脑水肿程度明显增加(P<0.05),HMGB1与RAGE的mRNA与蛋白表达明显增加(P<0.05),凋亡蛋白Cleaved-Caspase-3、Bax蛋白表达增加(P<0.05),BCFB紧密连接蛋白Claudin-5与ZO-1蛋白表达减少(P<0.05);与MCAO组相比,Lidoc-M与Lidoc-H组大鼠神经功能评分、脑梗死体积、透过BCFB的伊文思蓝含量与脑水肿程度明显减少(P<0.05),高迁移率族蛋白B1(HMGB1)与糖基化终产物受体(RAGE)的mRNA与蛋白表达明显减少(P<0.05),凋亡蛋白Cleaved-Caspase-3、Bax蛋白表达减少(P<0.05),BCFB紧密连接蛋白Claudin-5与ZO-1蛋白表达增加(P<0.05).结论利多卡因可能通过HMGB1/RAGE信号以通路保护BCFB紧密连接完整性,发挥抗缺血性卒中作用.

细胞表面抗体相关的自身免疫性脑炎短期预后的影响因素

目的 分析细胞表面抗体相关的自身免疫性脑炎(sAE)短期预后的影响因素。方法 收集郑州大学第一附属医院2019-06—2022-10首次被诊断为sAE的患者98例,分为预后良好组和预后不良组,对sAE患者的一般资料、临床特征、脑脊液检查及短期预后进行回顾性分析。结果 预后良好组和预后不良组比较,起病状态差异有统计学意义(P<0.05);2组血-脑屏障通透性明显不同,差异有统计学意义(P=0.005);预后良好组脑脊液寡克隆蛋白和IgG商与预后不良组比较,差异有统计学意义(P<0.05)。纳入多因素分析后,起病状态(OR=5.303,95%CI 1.225~22.961,P<0.05),血-脑屏障通透性改变(OR=4.485,95%CI 1.063~18.922,P<0.05)与sAE患者预后相关。结论 起病状态、血-脑屏障通透性是影响sAE患者短期预后的因素。

突变风与列车风耦合气动载荷下风屏障的强度分析

自然风与列车风的耦合气动作用是铁路风屏障产生弯曲、扭转等变形的主要原因。建立了列车-风屏障耦合的三维气动仿真模型,对风屏障在突变风与列车风耦合作用下压力分布规律进行了分析。建立了风屏障固体结构分析模型,对风屏障进行了模态分析,采用流固耦合的方法分析了风屏障在不同工况下的应力及变形量,据此对风屏障进行了强度校核。结果表明:风屏障自振频率最小为6.11 Hz,风屏障自振频率与列车风的振动频率相差较多,不会产生共振现象。在突变风与列车风耦合下,突变风的作用效果对风屏障的位移以及应力变化起决定性作用。在1.59 s时,风屏障在突变风与列车风耦合作用下产生最大位移,其中最大负位移达到1.42 mm,最大正位移达到0.605 mm。H形钢立柱产生最大的Mises应力,达到83.79 MPa,比列车风单独作用时增加了152.8%。可见突变风与列车风耦合会加剧风屏障的动力响应。

不同护栏透风率下桥面雪飘移的数值模拟

采用计算流体动力学(Computational Fluid Dynamics,CFD)方法,对典型桥梁断面上的雪飘移进行了数值模拟,得到桥面上风致积雪的重分布。为验证该文数值模拟方法的正确性,以平屋面风吹雪为案例,将该文数值模拟方法得到的结果与风洞试验结果进行了对比。在桥面雪飘移的数值模拟过程中,考虑了桥梁护栏的影响,对比分析了不同护栏透风率下桥面风致积雪重分布形式。研究发现:当护栏透风率大于50%时,桥面上不会出现显著的积雪沉积;当护栏透风率小于50%时,桥面护栏附近出现了较显著的积雪沉积,且在迎风端护栏的背风侧沉积最大。为减小桥面风致积雪堆积对交通的不利影响,建议在桥梁设计时采用高透风率的护栏。