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Reversibility of visual field defects through induction of brain plasticity: vision restoration, recovery and rehabilitation using alternating current stimulation

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Neural Regeneration Research 2020年第10期15卷 1799-1806页

作者： bernhard a.sabel Ying Gao Andrea Antal Institute of Medical Psychology Medical FacultyOtto-von-Guericke University of MagdeburgMagdeburgGermany Center for Behavioral and Brain Sciences(CBBS) MagdeburgGermany sabel Vision Restoration Center MagdeburgGermany Department of Clinical Neurophysiology University Medical Center GottingenGottingenGermany

For decades visual field defects were considered irreversible because it was thought that in the visual system the regeneration potential of the neuronal tissues is ***,there is always some potential for partial recovery of the visual field defect that can be achieved through induction of *** refers to the ability of the brain to change its own functional architecture by modulating synaptic *** is maintained throughout life and just as neurological rehabilitation can improve motor coordination,visual field defects in glaucoma,diabetic retinopathy or optic neuropathy can be improved by inducing *** ophthalmology many new treatment paradigms have been tested that can induce neuroplastic changes,including non-invasive alternating current *** with alternating current stimulation(e.g.,30 minutes,daily for 10 days using transorbital electrodes and^10 Hz)activates the entire retina and parts of the *** and functional magnetic resonance imaging studies revealed local activation of the visual cortex,global reorganization of functional brain networks,and enhanced blood flow,which together activate neurons and their *** future of low vision is optimistic because vision loss is indeed,partially reversible.

关键词： alternating current stimulation glaucoma low vision optic nerve rehabilitation recovery stress vision vision restoration therapy visual field

Nanoparticles as a tool to deliver drugs to the retina and brain:an update

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Neural Regeneration Research 2021年第2期16卷 283-284页

作者： Qing You bernhard a.sabel Institute of Medical Psychology Otto-von-Guericke University of MagdeburgMedical FacultyMagdeburgGermany

Over the past few years,different neurontargeted nanoparticles(NPs)were designed to deliver drugs to enhance neuron protection and recovery,and much progress was made in our understanding of the uptake mechanism and the related physicochemical *** properties attracting much attentions in NP's design and modification include particle size,surface hydrophobicity。

关键词： attracting drugs deliver

Non-invasive electrical brain stimulation:from acute to late-stage treatment of central nervous system damage

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Neural Regeneration Research 2017年第10期12卷 1590-1594页

作者： Petra Henrich-Noack Elena G.Sergeeva bernhard a.sabel Institute of Medical Psychology Otto-von-Guericke University Magdeburg Department of Emergency Medicine Emory University

Non-invasive brain current stimulation（NIBS） is a promising and versatile tool for inducing neuroplasticity,protection and functional rehabilitation of damaged neuronal *** is technically simple,requires no surgery,and has significant beneficial ***,there are various technical approaches for NIBS which influence neuronal networks in significantly different *** direct current stimulation（t DCS）,alternating current stimulation（ACS） and repetitive transcranial magnetic stimulation（r TMS） all have been applied to modulate brain activity in animal experiments under normal and pathological *** clinical trials have shown that t DCS,r TMS and ACS induce significant behavioural effects and can – depending on the parameters chosen – enhance or decrease brain excitability and influence performance and learning as well as rehabilitation and protective *** diverse phaenomena and partially opposing effects of NIBS are not yet fully understood and mechanisms of action need to be explored further in order to select appropriate parameters for a given task,such as current type and strength,timing,distribution of current densities and electrode *** this review,we will discuss the various parameters which need to be considered when designing a NIBS protocol and will put them into context with the envisaged applications in experimental neurobiology and medicine such as vision restoration,motor rehabilitation and cognitive enhancement.

关键词： non-invasive brain stimulation transcranial direct current stimulation transcranial magnetic stimulation transorbital alternating current stimulation stroke trauma neuroprotection restoration of function

Gene therapy with caspase-3 small interfering RNA-nanoparticles is neuroprotective after optic nerve damage

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Neural Regeneration Research 2021年第12期16卷 2534-2541页

作者： Mohamed Tawfik Xiwei Zhang Lisa Grigartzik Peter Heiduschka Werner Hintz Petra Henrich-Noack Berend van Wachem bernhard a.sabel Institute of Medical Psychology Otto von Guericke University of MagdeburgMagdeburgGermany Institute of Process Engineering Otto von Guericke University of MagdeburgMagdeburgGermany Department of Ophthalmology Münster University HospitalMünsterGermany Department of Neurology with Institute of Translational Neurology Münster University HospitalMünsterGermany Center of Behavioral Brain Sciences(CBBS) MagdeburgGermany

Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system *** developed a novel,non-viral gene therapy to block caspase-3 gene expression using small interfering RNA(siRNA)delivered by polybutylcyanoacrylate nanoparticles(CaspNPs).In vitro CaspNPs significantly blocked caspase-3 protein expression in C6 cells,and when injected intraocularly in vivo,CaspNPs lowered retinal capsase-3 immunofluorescence by 57.9%in rats with optic nerve ***,repeated retinal ganglion cell counts using confocal neuroimaging showed that post-traumatic cell loss after intraocular CaspNPs injection was only 36.1%versus 63.4%in lesioned *** non-viral gene therapy with siRNA-nanoparticles can selectively silence caspace-3 gene expression and block apoptosis in post-mitotic neurons,siRNA delivery with nanoparticles may be promising for neuroprotection or restoration of central visual system damage and other neurological *** animal study procedures were approved by the German National Act on the use of experimental animals(Ethic Committee Referat Verbraucherschutz,Veterinärangelegenheiten;Landesverwaltungsamt Sachsen-Anhalt,Halle,Germany,#IMP/G/01-1150/12 and#IMP/G/01-1469/17).

关键词： apoptosis brain caspase-3 drug delivery gene therapy in vivo confocal neuroimaging nanoparticles neurodegeneration neuroprotection retina siRNA

颅内压与眼内压的相关性及对视神经的影响：北京颅眼压力研究(iCOP)

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中国科学：生命科学 2016年第12期46卷 1413-1422页

作者：侯若武章征杨迪亚王怀洲陈伟伟李臻桑景荭刘苏萌曹怡雯谢晓斌任若瑾张亚卓 bernhard a.sabel 王宁利首都医科大学附属北京同仁医院神经外科北京100730 首都医科大学附属北京同仁医院眼科中心北京市眼科学及视觉科学重点实验室北京100730 北京市眼科研究所北京100730 首都医科大学附属北京宣武医院眼科北京100053 中国中医学院眼科医院眼科北京100040 Eye center New York Eye and Ear Infirmary New York 10003 USA 首都医科大学附属北京天坛医院北京市神经外科研究所神经外科北京100050 Institute of Medical Psychology Medical Faculty Otto-v.-Guericke University of Magdeburg Magdeburg 39120 Germany

通过逐渐梯度降低颅内压,明确颅内压逐渐降低过程中颅内压与与眼内压之间的关系及对视神经的影响,揭示颅内压降低导致压力相关性视神经损害的可能机理.采用8条实验用比格犬,分别于左侧侧脑室、左眼前房、左侧视神经蛛网膜下腔和腰大池... 详细信息

通过逐渐梯度降低颅内压,明确颅内压逐渐降低过程中颅内压与与眼内压之间的关系及对视神经的影响,揭示颅内压降低导致压力相关性视神经损害的可能机理.采用8条实验用比格犬,分别于左侧侧脑室、左眼前房、左侧视神经蛛网膜下腔和腰大池内植入测压探头,同时监测颅内压、眼内压、视神经蛛网膜下腔压力和腰大池压力的变化.于右侧侧脑室内植入脑室外引流管,逐渐引流脑脊液实现梯度降低颅内压.对比分析基线和逐渐梯度下降过程中颅内压、眼内压、视神经蛛网膜下腔压力和腰大池压力之间的变化和关系,进而明确颅内压与眼内压之间的关系曲线.基线时,颅内压、眼内压、视神经蛛网膜下腔压力和腰大池压力各不相等且颅内压大于腰大池压力,而腰大池压力大于视神经蛛网膜下腔压力.跨筛板压力梯度在眼内压减视神经蛛网膜下腔压力时最大,次之为眼内压减腰大池压力,最小的是眼内压减颅内压.随着颅内压逐渐梯度下降,在一定范围内眼内压随着颅内压的降低而下降,此时跨筛板压力梯度保持相对稳定(即颅眼压力依赖区);但是,当颅内压降低超过某一阈值(即分界点)后,眼内压与颅内压相互分离(即颅眼压力非依赖区),此时跨筛板压力梯度因颅内压的降低而增大.因此,颅内压与眼内压在颅眼压力依赖区内相互协调,有助于保持跨筛板压力梯度的稳定.当颅内压降低超过某一阈值后,颅内压与眼内压之间的这种平衡被打破(即颅眼压力非依赖区)会导致跨筛板压力梯度升高.同时,颅内压降低会导致视神经压力梯度和跨视神经压力梯度升高,阻碍了脑脊液从颅内压蛛网膜下腔流入到视神经蛛网膜下腔,从而引起不同程度视神经损害的发生.

关键词：青光眼视神经损害跨筛板压力梯度跨视神经管压力梯度跨视神经压力梯度视神经压力梯度

Pressure balance and imbalance in the optic nerve chamber： The Beijing Intracranial and Intraocular Pressure (iCOP) Study

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Science China(Life Sciences) 2016年第5期59卷 495-503页

作者： Ruowu Hou Zheng Zhang Diya Yang Huaizhou Wang Weiwei Chen Zhen Li Jinghong Sang Sumeng Liu Yiwen Cao Xiaobin Xie Ruojing Ren Yazhuo Zhang bernhard A. sabel Ningli Wang Department of Neurosurgery Beijing Tongren Hospital Capital Medical University Beijing 100730 China Beijing Tongren Eye Center Beijing Tongren Hospital Capital Medical University Beijing Ophthalmology and Visual Sciences Key Laboratory Beijing 100730 China Beijing Institute of Ophthalmology Beijing Tongren Hospital Capital Medical University Beijing 100730 China Department of Ophthalmology Xuanwu Hospital Capital Medical University Beijing 100053 China Department of Ophthalmology Eye Hospital of China Academy of Chinese Medical Sciences Beijing 100040 China Eye center New York Eye and Ear Infirmary New York 10003 USA Department of Endoscopic and Microinvasive Neurosurgery Beijing Neurosurgery Institute Beijing Tiantian Hospital Capital Medical University Beijing 100050 China Institute of Medical Psychology Medical Faculty Otto-v.-Guericke University of Magdeburg Magdeburg 39120 Germany

To determine the interdependence of intracranial pressure(ICP) and intraocular pressure(IOP) and how it affects optic nerve pressures, eight normal dogs were examined using pressure-sensing probes implanted into the left ventricle, lumbar cistern, optic nerve subarachnoid space in the left eye, and anterior chamber in the left eye. This allowed ICP, lumbar cistern pressure(LCP), optic nerve subarachnoid space pressure(ONSP) and IOP to be simultaneously recorded. After establishing baseline pressure levels, pressure changes that resulted from lowering ICP(via shunting cerebrospinal fluid(CSF) from the ventricle) were recorded. At baseline, all examined pressures were different(ICP>LCP>ONSP), but correlated(P<0.001). As ICP was lowered during CSF shunting, IOP also dropped in a parallel time course so that the trans-lamina cribrosa gradient(TLPG) remained stable(ICP-IOP dependent zone). However, once ICP fell below a critical breakpoint, ICP and IOP became uncoupled and TLPG changed as ICP declined(ICP-IOP independent zone). The optic nerve pressure gradient(ONPG) and trans-optic nerve pressure gradient(TOPG) increased linearly as ICP decreased through both the ICP-IOP dependent and independent zones. We conclude that ICP and IOP are coupled in a specific pressure range, but when ICP drops below a critical point, IOP and ICP become uncoupled and TLPG increases. When ICP drops, a rise in the ONPG and TOPG creates more pressure and reduces CSF flow around the optic nerve. This change may play a role in the development and progression of various ophthalmic and neurological diseases, including glaucoma.

关键词： glaucoma optic neuropathy trans-lamina cribrosa pressure gradient (TLPG) trans-optic canal pressure gradient(TCPG) trans-optic nerve pressure gradient (TOPG) optic nerve pressure gradient (ONPG)

Fertility and sexual life of men after their forties and in older age

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Asian Journal of Andrology 2001年第1期3卷 1-7页

作者： Wolf-bernhard Schill Department of Dermatoloyg and Andrology Hessian Center of Reprocuctive Medicine Justus Liebig University Giessen Germany

Owing to the demographic development, the aging male will require more consideration in future. In contrast to arapid decline of estradiol during menopause in women, the process of aging in the male is retarded and subject to highindividual variations. Impairment of spermatogenesis is observed as a continuous process occurring over decades. How-ever, only about 50% of men in their eighties show complete loss of fertility. In principle, spermatogenesis may be re-tained well into senescence. Of importance for the individual health condition is the fact that the number of Leydig cellsdeclines with advancing age. Thus, altered sex hormone concentrations in aging men result from both functional distur-bances and a gradual reduction in Leydig cells. Furthermore, an impaired feed-back mechanism of the pituitary-gonadalaxis occurs, with disappearance of the circadian testosterone (T) rhythm. LH and FSH levels are increased, and a re-duced bioavailability of sex hormones is observed. Lower total testosterone concentrations in men over 60 years are ac-companied by clinical signs of reduced virility, such as decreased muscle mass and strength as well as reduced sexualhair growth and libido. An age-related decline in androgen secretion and plasma testosterone levels therefore suggeststhe use of androgen supplementation. However, there is a lack of risk-benefit long-term studies. Increased research inthe male is mandatory to meet the requirements of the aging population. This should include the availability of preciseepidemiological data about the frequency of partial androgen deficiency in aging males (PADAM).(Asian J Androl 2001 Mar; 3: 1-7)

关键词： aging spermatogenesis androgens testosterone supplementation

Discussion of sources of error in laser-speckle based systems

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Chinese Optics Letters 2011年第7期9卷 41-44页

作者： bernhard G.Zogar Institute for Measurement Technology Johannes Kepler University Altenbergerstraβe 69 4040 Linz Austria

Applying laser-speckle techniques in material sciences as well as in methods to characterize surface con- ditions of specimen has become the method of choice, especially if a non-contacting principle is sought. This is almost always the case for specimen that are small in at least one dimension as for example in the materiM testing of foils, fibres, or micromaterials and certainly also if elevated test-temperatures are preventing standard gauges. This letter discusses in some detail sources of error that are quite often over- looked or not even considered as significant at all, but still carry the potential to introduce uncertainties well above the system design specifications.

关键词： Discussion of sources of error in laser-speckle based systems

Continuous Casting of Demanding HSLA Steel Grades for Heavy Plate Application

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Journal of Iron and Steel Research International 2011年第S1期18卷 535-540页

作者： bernhard Hoh Process Technology Steel Eichenweg 2546569 HuenxeGermany

Continuous casting has evolved as the most important production process in the steel *** it counts for about 95% of the world’s steel *** to its rising significance,the process technologies have been enhanced in yield,productivity and-in particular quality of semi-finished products has been improved close to the realm of *** optimizing the product quality beyond the present status has to put the whole manufacturing route from hot metal and/or steel melting through refining to continuous casting under integrated *** for the production of HSLA steel grades of the highest standard are clean steel,internal soundness and defect-free slab *** this context a brief look is cast on the recent trend of process technology in casting "thick slabs" for extra-heavy plate production.

关键词： HSLA steel integrated process control clean steel heavy slab surface cracking segregation heavy plate