The myelin sheath is a lipoprotein-rich,multilayered structure capable of increasing conduction velocity in central and peripheral myelinated nerve fibers.Due to the complex structure and composition of myelin,various...The myelin sheath is a lipoprotein-rich,multilayered structure capable of increasing conduction velocity in central and peripheral myelinated nerve fibers.Due to the complex structure and composition of myelin,various histological techniques have been developed over the centuries to evaluate myelin under normal,pathological or experimental conditions.Today,methods to assess myelin integrity or content are key tools in both clinical diagnosis and neuroscience research.In this review,we provide an updated summary of the composition and structure of the myelin sheath and discuss some histological procedures,from tissue fixation and processing techniques to the most used and practical myelin histological staining methods.Considering the lipoprotein nature of myelin,the main features and technical details of the different available methods that can be used to evaluate the lipid or protein components of myelin are described,as well as the precise ultrastructural techniques.展开更多
Astrocytes are indispensable for central nervous system development and homeostasis.In response to injury and disease,astrocytes are integral to the immunological-and the,albeit limited,repair response.In this review,...Astrocytes are indispensable for central nervous system development and homeostasis.In response to injury and disease,astrocytes are integral to the immunological-and the,albeit limited,repair response.In this review,we will examine some of the functions reactive astrocytes play in the context of multiple sclerosis and related animal models.We will consider the heterogeneity or plasticity of astrocytes and the mechanisms by which they promote or mitigate demyelination.Finally,we will discuss a set of biomedical strategies that can stimulate astrocytes in their promyelinating response.展开更多
In the last decade,a new neurological disease concept known as anti-myelin oligodendrocyte glycoprotein antibody(MOG-IgG)-associated disease(MOGAD)has emerged and is currently one of the most focused research areas in...In the last decade,a new neurological disease concept known as anti-myelin oligodendrocyte glycoprotein antibody(MOG-IgG)-associated disease(MOGAD)has emerged and is currently one of the most focused research areas in the field of neuroimmunology.MOG is a membrane protein mainly expressed on the surface of oligodendrocytes(Zhou et al.,2006).The exact pathogenic role of MOG-IgG in patients with MOGAD remains unclear;however,MOG-IgG has been suggested to cause tissue alterations and damage MOG-expressing cells(Zhou et al.,2006).The pathogenicity of MOG-IgG is further supported by the observation that only a few patients with acquired central nervous system(CNS)demyelinating syndromes exhibit both anti-aquaporin-4 antibody(AQP4-IgG)and MOG-IgG simultaneously,particularly with clear positivity levels of these antibodies as indicated by a cell-based assay result with a titer≥1:100(Sechi et al.,2021;Banwell et al.,2023).展开更多
Piezo1 is a mechanically-gated calcium channel.Recent studies have shown that Piezo1,a mechanically-gated calcium channel,can attenuate both psychosineand lipopolysaccharide-induced demyelination.Because oligodendrocy...Piezo1 is a mechanically-gated calcium channel.Recent studies have shown that Piezo1,a mechanically-gated calcium channel,can attenuate both psychosineand lipopolysaccharide-induced demyelination.Because oligodendrocyte damage and demyelination occur in intracerebral hemorrhage,in this study,we investigated the role of Piezo1 in intracerebral hemorrhage.We established a mouse model of cerebral hemorrhage by injecting autologous blood into the right basal ganglia and found that Piezo1 was largely expressed soon(within 48 hours)after intracerebral hemorrhage,primarily in oligodendrocytes.Intraperitoneal injection of Dooku1 to inhibit Piezo1 resulted in marked alleviation of brain edema,myelin sheath loss,and degeneration in injured tissue,a substantial reduction in oligodendrocyte apoptosis,and a significant improvement in neurological function.In addition,we found that Dooku1-mediated Piezo1 suppression reduced intracellular endoplasmic reticulum stress and cell apoptosis through the PERK-ATF4-CHOP and inositol-requiring enzyme 1 signaling pathway.These findings suggest that Piezo1 is a potential therapeutic target for intracerebral hemorrhage,as its suppression reduces intracellular endoplasmic reticulum stress and cell apoptosis and protects the myelin sheath,thereby improving neuronal function after intracerebral hemorrhage.展开更多
Circular RNAs(circRNAs)play a vital role in diabetic peripheral neuropathy.However,their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood.Here,we per...Circular RNAs(circRNAs)play a vital role in diabetic peripheral neuropathy.However,their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood.Here,we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls.Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group.Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation.A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circRNAs.circ_0002538 was markedly downregulated in patients with diabetic peripheral neuropathy.Further in vitro experiments showed that overexpression of circ_0002538 promoted the migration of Schwann cells by upregulating plasmolipin(PLLP)expression.Moreover,overexpression of circ_0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function.The results of a mechanistic experiment showed that circ_0002538 promotes PLLP expression by sponging miR-138-5p,while a lack of circ_0002538 led to a PLLP deficiency that further suppressed Schwann cell migration.These findings suggest that the circ_0002538/miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients,improving myelin sheath structure and nerve function.Thus,this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy.展开更多
Schwann cells,the myelinating glia of the peripheral nervous system,wrap axons multiple times to build their myelin sheath.Myelin is of paramount importance for axonal integrity and fast axon potential propagation.How...Schwann cells,the myelinating glia of the peripheral nervous system,wrap axons multiple times to build their myelin sheath.Myelin is of paramount importance for axonal integrity and fast axon potential propagation.However,myelin is lacking or dysfunctional in several neuropathies including demyelinating and dysmyelinating Charcot-M arie-To oth disease.Charcot-Marie-To oth disease represents the most prevalent inherited neuropathy in humans and is classified either as axonal,demyelinating or dysmyelinating,or as intermediate.The demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease constitute the majority of the disease cases and are most frequently due to mutations in the three following myelin genes:peripheral myelin protein 22,myelin protein ze ro and gap junction beta 1(coding for Connexin 32) causing Charcot-M arie-Tooth disease type 1A,Charcot-Marie-Tooth disease type 1B,and X-linked Charcot-M arie-Tooth disease type 1,respectively.The resulting perturbation of myelin structure and function leads to axonal demyelination or dysmyelination and causes severe disabilities in affected patients.No treatment to cure or slow down the disease progression is currently available on the market,howeve r,scientific discoveries led to a better understanding of the pathomechanisms of the disease and to potential treatment strategies.In this review,we describe the features and molecular mechanisms of the three main demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease,the rodent models used in research,and the emerging therapeutic approaches to cure or counteract the progression of the disease.展开更多
Spinal cord injuries affect nearly five to ten individuals per million every year. Spinal cord injury causes damage to the nerves, muscles, and the tissue surrounding the spinal cord. Depending on the severity, spinal...Spinal cord injuries affect nearly five to ten individuals per million every year. Spinal cord injury causes damage to the nerves, muscles, and the tissue surrounding the spinal cord. Depending on the severity, spinal injuries are linked to degeneration of axons and myelin, resulting in neuronal impairment and skeletal muscle weakness and atrophy. The protection of neurons and promotion of myelin regeneration during spinal cord injury is important for recovery of function following spinal cord injury. Current treatments have little to no effect on spinal cord injury and neurogenic muscle loss. Clemastine, an Food and Drug Administration-approved antihistamine drug, reduces inflammation, protects cells, promotes remyelination, and preserves myelin integrity. Recent clinical evidence suggests that clemastine can decrease the loss of axons after spinal cord injury, stimulating the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes that are capable of myelination. While clemastine can aid not only in the remyelination and preservation of myelin sheath integrity, it also protects neurons. However, its role in neurogenic muscle loss remains unclear. This review discusses the pathophysiology of spinal cord injury, and the role of clemastine in the protection of neurons, myelin, and axons as well as attenuation of skeletal muscle loss following spinal cord injury.展开更多
The formation of axonal spheroid is a common feature following spinal cord injury.To further understand the source of Ca^(2+)that mediates axonal spheroid formation,we used our previously characterized ex vivo mouse s...The formation of axonal spheroid is a common feature following spinal cord injury.To further understand the source of Ca^(2+)that mediates axonal spheroid formation,we used our previously characterized ex vivo mouse spinal cord model that allows precise perturbation of extracellular Ca^(2+).We performed twophoton excitation imaging of spinal cords isolated from Thy1YFP+transgenic mice and applied the lipophilic dye,Nile red,to record dynamic changes in dorsal column axons and their myelin sheaths respectively.We selectively released Ca^(2+)from internal stores using the Ca^(2+)ionophore ionomycin in the presence or absence of external Ca^(2+).We reported that ionomycin dose-dependently induces pathological changes in myelin and pronounced axonal spheroid formation in the presence of normal 2 m M Ca^(2+)artificial cerebrospinal fluid.In contrast,removal of external Ca^(2+)significantly decreased ionomycin-induced myelin and axonal spheroid formation at 2 hours but not at 1 hour after treatment.Using mice that express a neuron-specific Ca^(2+)indicator in spinal cord axons,we confirmed that ionomycin induced significant increases in intra-axonal Ca^(2+),but not in the absence of external Ca^(2+).Periaxonal swelling and the resultant disruption in the axo-myelinic interface often precedes and is negatively correlated with axonal spheroid formation.Pretreatment with YM58483(500 n M),a well-established blocker of store-operated Ca^(2+)entry,significantly decreased myelin injury and axonal spheroid formation.Collectively,these data reveal that ionomycin-induced depletion of internal Ca^(2+)stores and subsequent external Ca^(2+)entry through store-operated Ca^(2+)entry contributes to pathological changes in myelin and axonal spheroid formation,providing new targets to protect central myelinated fibers.展开更多
Remyelination and need to access it:A range of diseases such as Guillain-Barre syndrome,Pelizaeus Merzbacher disease,relapsing-remitting and secondary progressive multiple sclerosis is associated with various degrees ...Remyelination and need to access it:A range of diseases such as Guillain-Barre syndrome,Pelizaeus Merzbacher disease,relapsing-remitting and secondary progressive multiple sclerosis is associated with various degrees of nerve demyelination.These diseases present with various degrees of demyelination and differentclinical manifestations.展开更多
We systematically study the evolution of modulated nerve impulses in a myelinated nerve fiber, where both the ionic current and membrane capacitance provide the necessary nonlinear feedbacks. This is achieved by using...We systematically study the evolution of modulated nerve impulses in a myelinated nerve fiber, where both the ionic current and membrane capacitance provide the necessary nonlinear feedbacks. This is achieved by using a perturbation technique, in which the Liénard form of the modified discrete Fitzhugh–Nagumo equation is reduced to the complex Ginzburg–Landau amplitude equation. Three distinct values of the capacitive feedback parameter are considered. At the critical value of the capacitive feedback parameter, it is shown that the dynamics of the system is governed by the dissipative nonlinear Schr?dinger equation. Linear stability analysis of the system depicts the instability of plane waves,which is manifested as burst of modulated nerve impulses that fulfills the Benjamin–Feir criteria. Variations of the capacitive feedback parameter generally influences the plane wave stability and hence the type of wave profile identified in the neural network. Results of numerical simulations mainly confirm the propagation, collision, and annihilation of nerve impulses in the myelinated axon.展开更多
Rosmarinic acid,a common ester extracted from Rosemary,Perilla frutescens,and Salvia miltiorrhiza Bunge,has been shown to have protective effects against various diseases.This is an investigation into whether rosmarin...Rosmarinic acid,a common ester extracted from Rosemary,Perilla frutescens,and Salvia miltiorrhiza Bunge,has been shown to have protective effects against various diseases.This is an investigation into whether rosmarinic acid can also affect the changes of white matter fibers and cognitive deficits caused by hypoxic injury.The right common carotid artery of 3-day-old rats was ligated for 2 hours.The rats were then prewarmed in a plastic container with holes in the lid,which was placed in 37°C water bath for 30 minutes.Afterwards,the rats were exposed to an atmosphere with 8% O2 and 92% N2 for 30 minutes to establish the perinatal hypoxia/ischemia injury models.The rat models were intraperitoneally injected with rosmarinic acid 20 mg/kg for 5 consecutive days.At 22 days after birth,rosmarinic acid was found to improve motor,anxiety,learning and spatial memory impairments induced by hypoxia/ischemia injury.Furthermore,rosmarinic acid promoted the proliferation of oligodendrocyte progenitor cells in the subventricular zone.After hypoxia/ischemia injury,rosmarinic acid reversed to some extent the downregulation of myelin basic protein and the loss of myelin sheath in the corpus callosum of white matter structure.Rosmarinic acid partially slowed down the expression of oligodendrocyte marker Olig2 and myelin basic protein and the increase of oligodendrocyte apoptosis marker inhibitors of DNA binding 2.These data indicate that rosmarinic acid ameliorated the cognitive dysfunction after perinatal hypoxia/ischemia injury by improving remyelination in corpus callosum.This study was approved by the Animal Experimental Ethics Committee of Xuzhou Medical University,China (approval No.20161636721) on September 16,2017.展开更多
Our lab has shown that brief electrical nerve stimulation(ES)has a dramatic impact on remyelination of lysophosphatidyl choline(LPC)-induced focally demyelinated rat peripheral nerves,while also inducing an axon-prote...Our lab has shown that brief electrical nerve stimulation(ES)has a dramatic impact on remyelination of lysophosphatidyl choline(LPC)-induced focally demyelinated rat peripheral nerves,while also inducing an axon-protective phenotype and shifting macrophages from a predominantly pro-inflammatory toward a pro-repair phenotype.Whether this same potential exists in the central nervous system is not known.Thus,for proof of principle studies,the peripheral nerve demyelination and ES model was adapted to the central nervous system,whereby a unilateral focal LPC-induced demyelination of the dorsal column at the lumbar enlargement where the sciatic nerve afferents enter was created,so that subsequent ipsilateral sciatic nerve ES results in increased neural activity in the demyelinated axons.Data reveal a robust focal demyelination at 7 days post-LPC injection.Delivery of 1-hour ES at 7 days post-LPC polarizes macrophages/microglia toward a pro-repair phenotype when examined at 14 days post-LPC;results in smaller LPC-associated regions of inflammation compared to non-stimulated controls;results in significantly more cells of the oligodendroglial lineage in the demyelinated region;elevates myelin basic protein levels;and shifts the paranodal protein Caspr along demyelinated axons to a more restricted distribution,consistent with reformation of the paranodes of the nodes of Ranvier.ES also significantly enhanced levels of phosphorylated neurofilaments detected in the zones of demyelination,which has been shown to confer axon protection.Collectively these findings support that strategies that increase neural activity,such as brief electrical stimulation,can be beneficial for promoting intrinsic repair following focal demyelinating insults in demyelinating diseases such as multiple sclerosis.All animal procedures performed were approved by the University of Saskatchewan's Animal Research Ethics Board(protocol#20090087;last approval date:November 5,2020).展开更多
BACKGROUND:Acupuncture treatment on injured cerebral axons has shown to provide efficacy in clinical practice.It is unknown whether acupuncture produces therapeutic effects by protecting injured cerebral myelin in isc...BACKGROUND:Acupuncture treatment on injured cerebral axons has shown to provide efficacy in clinical practice.It is unknown whether acupuncture produces therapeutic effects by protecting injured cerebral myelin in ischemic stroke.OBJECTIVE:To test whether acupuncture provides protection for injured cerebral myelin,based on quantitative data from cerebral ischemia-reperfusion rats,and to compare the effects of early and late acupuncture on serum myelin basic protein(MBP) content and remyelination of the ischemic internal capsule.DESIGN,TIME AND SETTING:A randomized,controlled experiment was performed at the Neuro-biological Laboratory,Sichuan University from March 2005 to March 2006.MATERIALS:"Hua Tuo" Brand filiform needles were produced by the Medical Instrument Factory of Suzhou,China.METHODS:A total of 52 adult,healthy,male,Sprague Dawley rats were randomly assigned to four groups:control(n=4),model(n=16),early acupuncture(n=16),and late acupuncture(n=16).The focal cerebral ischemia-reperfusion model was established by middle cerebral artery occlusion in the right hemisphere using the modified thread embolism method in the latter three groups.Early and late acupuncture groups underwent acupuncture after ischemia for 30 minutes and 2 hours using the Xingnaokaiqiao needling method,respectively.Acupoints were "Neiguan"(PC 6) and "Sanyinjiao"(SP 6) on the bilateral sides,as well as "Shuigou"(DU 26) and "Baihui"(DU 20) with stimulation for 1 minute at each acupoint.Acupuncture at all acupoints was performed two or three times while the needle was retained,once per day.No special handling was administered to the control group.MAIN OUTCOME MEASURES:For each group,remyelination of the internal capsule was observed by Pal-Weigert's myelin staining and serum MBP content was detected using enzyme-linked immunosorbent assay method on days 1,3,5,and 7 following ischemia-reperfusion injury.RESULTS:Compared with the control group,massive demyelination of the internal capsule occurred,and serum MBP content increased in the model group(P<0.05).Compared with the model group,the extent of demyelination in the internal capsule was less distinct and serum MBP content was significantly less in the early and late acupuncture group(P<0.01).Compared with the late acupuncture group,serum MBP content reached a peak later and the peak value was less in the early acupuncture group.CONCLUSION:Results suggest that acupuncture exerts a protective effect on injured cerebral myelin in ischemia-reperfusion rats by reducing serum MBP content and promoting remyelination.The study also suggests that the effect of early acupuncture is superior to late acupuncture.展开更多
Neural plasticity in the adult central nervous system involves the adaptation of myelination, including the formation of novel myelin sheaths by adult-born oligodendrocytes. Yet, mature oligodendrocytes slowly but con...Neural plasticity in the adult central nervous system involves the adaptation of myelination, including the formation of novel myelin sheaths by adult-born oligodendrocytes. Yet, mature oligodendrocytes slowly but constantly turn over their pre-existing myelin sheaths, thereby establishing an equilibrium of replenishment and degradation that may also be subject to adaptation with consequences for nerve conduction velocity. In this short review we highlight selected approaches to the normal turnover of adult myelin in vivo, from injecting radioactive precursors of myelin constituents in the 1960s to current strategies involving isotope labeling and tamoxifen-induced gene targeting.展开更多
In this study, we investigated the clinical relevance of anti-myelin antibodies in patients with neuromyelitis optica (NMO);titers of antibodies against myelin oligodendrocyte glycoproteins, proteolipid proteins and m...In this study, we investigated the clinical relevance of anti-myelin antibodies in patients with neuromyelitis optica (NMO);titers of antibodies against myelin oligodendrocyte glycoproteins, proteolipid proteins and myelin basic proteins were measured in the sera of patients with NMO and compared to healthy controls, as well as to patients with other diseases. The frequency of presence of anti-myelin antibodies in patients with NMO was significantly higher than that in healthy and diseased controls. The expanded disability status scale scores correlated with the titers of the anti-myelin antibodies. Patients with anti-myelin antibody exhibited other autoantibodies significantly more frequently than patients without the antibody. Anti-myelin antibodies may be useful markers for predicting severe clinical courses in patients with NMO.展开更多
Since disability in multiple sclerosis(MS) is a product of neurodegeneration and deficient remyelination, the ability to enhance neuroregeneration and myelin regeneration in MS is an enticing goal for MS drug developm...Since disability in multiple sclerosis(MS) is a product of neurodegeneration and deficient remyelination, the ability to enhance neuroregeneration and myelin regeneration in MS is an enticing goal for MS drug development. In particular, remyelination treatments could promote return of neurological function and also prevent further axonal loss and neurodegeneration in MS due to trophic effects of myelin. The study of remyelination has advanced dramatically in the last several years such that a number of pathways inhibiting remyelination have been discovered, including those involving LINGO-1, Notch-1, hyaluronan, retinoid X receptor, and wnt/?-catenin. Other approaches such as high throughput drug screening for remyelination drugs have caught fire, with identification of dozens of known drugs with oligodendrocyte maturation stimulatory effects. Several drugs identified through screens and other mechanisms are in the process of being further evaluated for remyelination in MS and MS models. We discuss the potential molecular targets and the variety of mechanisms towards drug identification and development in remyelination for MS.展开更多
Salvianolic acid B,an active pharmaceutical compound present in Salvia miltiorrhiza,exerts a neuroprotective effect in animal models of brain and spinal cord injury.Salvianolic acid B can promote recovery of neurologi...Salvianolic acid B,an active pharmaceutical compound present in Salvia miltiorrhiza,exerts a neuroprotective effect in animal models of brain and spinal cord injury.Salvianolic acid B can promote recovery of neurological function;however,its protective effect on the myelin sheath after spinal cord injury remains poorly understood.Thus,in this study,in vitro tests showed that salvianolic acid B contributed to oligodendrocyte precursor cell differentiation,and the most effective dose was 20 μg/m L.For in vivo investigation,rats with spinal cord injury were intraperitoneally injected with 20 mg/kg salvianolic acid B for 8 weeks.The amount of myelin sheath and the number of regenerating axons increased,neurological function recovered,and caspase-3 expression was decreased in the spinal cord of salvianolic acid B-treated animals compared with untreated control rats.These results indicate that salvianolic acid B can protect axons and the myelin sheath,and can promote the recovery of neurological function.Its mechanism of action is likely to be associated with inhibiting apoptosis and promoting the differentiation and maturation of oligodendrocyte precursor cells.展开更多
Activation of the unfolded protein response in response to endoplasmic reticulum stress preserves cell viability and function under stressful conditions.Nevertheless,persistent,unresolvable activation of the unfolded ...Activation of the unfolded protein response in response to endoplasmic reticulum stress preserves cell viability and function under stressful conditions.Nevertheless,persistent,unresolvable activation of the unfolded protein response can trigger apoptosis to eliminate stressed cells.Recent studies show that the unfolded protein response plays an important role in the pathogenesis of various disorders of myelin,including multiples sclerosis,Charcot-Marie-Tooth disease,Pelizaeus-Merzbacher disease,vanishing white matter disease,spinal cord injury,tuberous sclerosis complex,and hypoxia-induced perinatal white matter injury.In this review we summarize the current literature on the unfolded protein response and the evidence for its role in the pathogenesis of myelin disorders.展开更多
AIM:To compare the thickness of the peripapillary retinal nerve fiber layer(RNFL)and ganglion cell-inner plexiform layer(GCIPL)among patients with various forms of optic neuritis(ON)and to identify whether any particu...AIM:To compare the thickness of the peripapillary retinal nerve fiber layer(RNFL)and ganglion cell-inner plexiform layer(GCIPL)among patients with various forms of optic neuritis(ON)and to identify whether any particular parameters or their thinning pattern can be used to distinguish the type of ON.METHODS:This prospective study was conducted at the Department of Ophthalmology,Faculty of Medicine,Siriraj Hospital,Thailand,between January,2015 and December,2016.We enlisted patients over 18 years of age with history of ON and categorized patients into 4 groups:1)aquaporin 4 antibodies(AQP4-IgG)positive;2)multiple sclerosis(MS);3)myelin oligodendrocyte glycoprotein antibodies(MOG-IgG)positive;4)idiopathic-ON patients.Healthy controls were also included during the same study period.All patients underwent complete ophthalmological examination and spectral domain optical coherence tomography(OCT)imaging to analyze RNFL and GCIPL thickness after at least 3mo since the last episode of acute ON.The generalized estimating equation(GEE)models were used to compare the data amongst ON groups. RESULTS: Among 87 previous ON eyes from 57 patients(43 AQP4-IgG+ON,17 MS-ON,8 MOG-IgG+ON,and 19idiopathic-ON),mean logMAR visual acuity of AQP4-IgG+ON,MS-ON,MOG-IgG+ON,and idiopathic-ON groups was 0.76±0.88,0.12±0.25,0.39±0.31,and 0.75±1.08,respectively.Average,superior,and inferior RNFL were significantly reduced in AQP4-IgG+ON,MOG-IgG+ON and idiopathic-ON eyes,relative to those of MS-ON.Differences were not statistically significant for RNFL or GCIPL between the AQP4-IgG+ON and MOG-IgG+ON groups,whereas visual acuity in MOG-IgG+ON was slightly,but not significantly,better(0.39 vs 0.76).Although RNFL thickness in MOG-IgG+ON was significantly reduced as compared to MS-ON,mean visual acuity and GCIPL were not different.CONCLUSION:Thinning of superior and inferior quadrants of RNFL are more commonly seen in MOG-IgG+ON and AQP4-IgG+ON.Long term visual acuity in MOG-IgG+ON is often better than AQP4-IgG+ON,whereas the structural change from OCT is comparable.展开更多
Multiple sclerosis(MS)is a neurodegenerative disease characterized by inflammation and demyelination.Studies are focused on encountering remyelination therapies that can be applied to delaying,or even decreasing,the m...Multiple sclerosis(MS)is a neurodegenerative disease characterized by inflammation and demyelination.Studies are focused on encountering remyelination therapies that can be applied to delaying,or even decreasing,the motor and cognitive disabilities caused by the disease.The cellular/molecular changes in MS are dynamic,with inflammation,demyelination and remyelination inducing progressive neurodegenerative changes in the central nervous system,as a whole.Moreover,the imaging methods for accompanying the process are,as yet,shortcoming.展开更多
基金supported by the Spanish“Plan Nacional de Investigación Científica,Desarrollo e Innovación Tecnológica,Ministerio de Economía y Competitividad(Instituto de Salud CarlosⅢ)”,Grant FIS PI20-0318 co-financed by“Fondo Europeo de Desarrollo Regional ERDF-FEDER European Union”Grant P18-RT-5059“Plan Andaluz de Investigación,Desarrollo e Innovación(PAIDI 2020),Consejería de Transformación Económica,Industria,Conocimiento y Universidades,Junta de Andalucía,Espana”(all to VC)Grant PPJIA202219“Ayudas del plan propio UGR 2022,Plan propio de investigación y transferencia,Universidad de Granada,Espana”(to JCA andóDGG)。
文摘The myelin sheath is a lipoprotein-rich,multilayered structure capable of increasing conduction velocity in central and peripheral myelinated nerve fibers.Due to the complex structure and composition of myelin,various histological techniques have been developed over the centuries to evaluate myelin under normal,pathological or experimental conditions.Today,methods to assess myelin integrity or content are key tools in both clinical diagnosis and neuroscience research.In this review,we provide an updated summary of the composition and structure of the myelin sheath and discuss some histological procedures,from tissue fixation and processing techniques to the most used and practical myelin histological staining methods.Considering the lipoprotein nature of myelin,the main features and technical details of the different available methods that can be used to evaluate the lipid or protein components of myelin are described,as well as the precise ultrastructural techniques.
基金supported by the Heart and Stroke Foundation and Ontario Institute of Regenerative Medicine (New Ideas Grant)Canada First Research Excellence Fund(Medicine by Design)+2 种基金the National Sciences and Engineering Research Councilthe Jurgen Manchot Foundationthe Christiane and Claudia Hempel Foundation for Clinical Stem Cell Research and the James and Elisabeth Cloppenburg,Peek and Cloppenburg Düsseldorf Stiftung (to PK)
文摘Astrocytes are indispensable for central nervous system development and homeostasis.In response to injury and disease,astrocytes are integral to the immunological-and the,albeit limited,repair response.In this review,we will examine some of the functions reactive astrocytes play in the context of multiple sclerosis and related animal models.We will consider the heterogeneity or plasticity of astrocytes and the mechanisms by which they promote or mitigate demyelination.Finally,we will discuss a set of biomedical strategies that can stimulate astrocytes in their promyelinating response.
文摘In the last decade,a new neurological disease concept known as anti-myelin oligodendrocyte glycoprotein antibody(MOG-IgG)-associated disease(MOGAD)has emerged and is currently one of the most focused research areas in the field of neuroimmunology.MOG is a membrane protein mainly expressed on the surface of oligodendrocytes(Zhou et al.,2006).The exact pathogenic role of MOG-IgG in patients with MOGAD remains unclear;however,MOG-IgG has been suggested to cause tissue alterations and damage MOG-expressing cells(Zhou et al.,2006).The pathogenicity of MOG-IgG is further supported by the observation that only a few patients with acquired central nervous system(CNS)demyelinating syndromes exhibit both anti-aquaporin-4 antibody(AQP4-IgG)and MOG-IgG simultaneously,particularly with clear positivity levels of these antibodies as indicated by a cell-based assay result with a titer≥1:100(Sechi et al.,2021;Banwell et al.,2023).
基金supported by the National Natural Science Foundation of China,Nos.81901193(to HLZ)and 81901267(to YY)。
文摘Piezo1 is a mechanically-gated calcium channel.Recent studies have shown that Piezo1,a mechanically-gated calcium channel,can attenuate both psychosineand lipopolysaccharide-induced demyelination.Because oligodendrocyte damage and demyelination occur in intracerebral hemorrhage,in this study,we investigated the role of Piezo1 in intracerebral hemorrhage.We established a mouse model of cerebral hemorrhage by injecting autologous blood into the right basal ganglia and found that Piezo1 was largely expressed soon(within 48 hours)after intracerebral hemorrhage,primarily in oligodendrocytes.Intraperitoneal injection of Dooku1 to inhibit Piezo1 resulted in marked alleviation of brain edema,myelin sheath loss,and degeneration in injured tissue,a substantial reduction in oligodendrocyte apoptosis,and a significant improvement in neurological function.In addition,we found that Dooku1-mediated Piezo1 suppression reduced intracellular endoplasmic reticulum stress and cell apoptosis through the PERK-ATF4-CHOP and inositol-requiring enzyme 1 signaling pathway.These findings suggest that Piezo1 is a potential therapeutic target for intracerebral hemorrhage,as its suppression reduces intracellular endoplasmic reticulum stress and cell apoptosis and protects the myelin sheath,thereby improving neuronal function after intracerebral hemorrhage.
基金supported by the National Natural Science Foundation of China,Nos.81772094(to ZBC),81974289(to ZBC)the Key Research and Development Program of Hubei Province,No.2020BCB031(to ZBC)Natural Science Foundation of Hubei Province,No.2020CFB433(to YTL).
文摘Circular RNAs(circRNAs)play a vital role in diabetic peripheral neuropathy.However,their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood.Here,we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls.Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group.Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation.A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circRNAs.circ_0002538 was markedly downregulated in patients with diabetic peripheral neuropathy.Further in vitro experiments showed that overexpression of circ_0002538 promoted the migration of Schwann cells by upregulating plasmolipin(PLLP)expression.Moreover,overexpression of circ_0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function.The results of a mechanistic experiment showed that circ_0002538 promotes PLLP expression by sponging miR-138-5p,while a lack of circ_0002538 led to a PLLP deficiency that further suppressed Schwann cell migration.These findings suggest that the circ_0002538/miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients,improving myelin sheath structure and nerve function.Thus,this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy.
基金supported by the Deutsche Forschungsgemeinshaft (to CJ)。
文摘Schwann cells,the myelinating glia of the peripheral nervous system,wrap axons multiple times to build their myelin sheath.Myelin is of paramount importance for axonal integrity and fast axon potential propagation.However,myelin is lacking or dysfunctional in several neuropathies including demyelinating and dysmyelinating Charcot-M arie-To oth disease.Charcot-Marie-To oth disease represents the most prevalent inherited neuropathy in humans and is classified either as axonal,demyelinating or dysmyelinating,or as intermediate.The demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease constitute the majority of the disease cases and are most frequently due to mutations in the three following myelin genes:peripheral myelin protein 22,myelin protein ze ro and gap junction beta 1(coding for Connexin 32) causing Charcot-M arie-Tooth disease type 1A,Charcot-Marie-Tooth disease type 1B,and X-linked Charcot-M arie-Tooth disease type 1,respectively.The resulting perturbation of myelin structure and function leads to axonal demyelination or dysmyelination and causes severe disabilities in affected patients.No treatment to cure or slow down the disease progression is currently available on the market,howeve r,scientific discoveries led to a better understanding of the pathomechanisms of the disease and to potential treatment strategies.In this review,we describe the features and molecular mechanisms of the three main demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease,the rodent models used in research,and the emerging therapeutic approaches to cure or counteract the progression of the disease.
基金supported in part by funding from the Veterans Administration (1IOBX001262, 1I01 BX004269)South Carolina State Spinal Cord Injury Research Fund (SCIRF-2015P-01, SCIRF-2015P-04, SCIRF-2015-I-01, SCIRF#2016 I-03, and SCIRF#2018 I-01)(to AH)+1 种基金supported in part by funding from the National Institutes of Health (1R21NS118393-01)(to AH)a Research Career Scientist award (#IK6BX005964) from the Department of veterans Affairs。
文摘Spinal cord injuries affect nearly five to ten individuals per million every year. Spinal cord injury causes damage to the nerves, muscles, and the tissue surrounding the spinal cord. Depending on the severity, spinal injuries are linked to degeneration of axons and myelin, resulting in neuronal impairment and skeletal muscle weakness and atrophy. The protection of neurons and promotion of myelin regeneration during spinal cord injury is important for recovery of function following spinal cord injury. Current treatments have little to no effect on spinal cord injury and neurogenic muscle loss. Clemastine, an Food and Drug Administration-approved antihistamine drug, reduces inflammation, protects cells, promotes remyelination, and preserves myelin integrity. Recent clinical evidence suggests that clemastine can decrease the loss of axons after spinal cord injury, stimulating the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes that are capable of myelination. While clemastine can aid not only in the remyelination and preservation of myelin sheath integrity, it also protects neurons. However, its role in neurogenic muscle loss remains unclear. This review discusses the pathophysiology of spinal cord injury, and the role of clemastine in the protection of neurons, myelin, and axons as well as attenuation of skeletal muscle loss following spinal cord injury.
文摘The formation of axonal spheroid is a common feature following spinal cord injury.To further understand the source of Ca^(2+)that mediates axonal spheroid formation,we used our previously characterized ex vivo mouse spinal cord model that allows precise perturbation of extracellular Ca^(2+).We performed twophoton excitation imaging of spinal cords isolated from Thy1YFP+transgenic mice and applied the lipophilic dye,Nile red,to record dynamic changes in dorsal column axons and their myelin sheaths respectively.We selectively released Ca^(2+)from internal stores using the Ca^(2+)ionophore ionomycin in the presence or absence of external Ca^(2+).We reported that ionomycin dose-dependently induces pathological changes in myelin and pronounced axonal spheroid formation in the presence of normal 2 m M Ca^(2+)artificial cerebrospinal fluid.In contrast,removal of external Ca^(2+)significantly decreased ionomycin-induced myelin and axonal spheroid formation at 2 hours but not at 1 hour after treatment.Using mice that express a neuron-specific Ca^(2+)indicator in spinal cord axons,we confirmed that ionomycin induced significant increases in intra-axonal Ca^(2+),but not in the absence of external Ca^(2+).Periaxonal swelling and the resultant disruption in the axo-myelinic interface often precedes and is negatively correlated with axonal spheroid formation.Pretreatment with YM58483(500 n M),a well-established blocker of store-operated Ca^(2+)entry,significantly decreased myelin injury and axonal spheroid formation.Collectively,these data reveal that ionomycin-induced depletion of internal Ca^(2+)stores and subsequent external Ca^(2+)entry through store-operated Ca^(2+)entry contributes to pathological changes in myelin and axonal spheroid formation,providing new targets to protect central myelinated fibers.
基金supported by the US Department of Defense Grant WH-X81160715Department of Health and Human Services I National Institutes of Health/National Eye Institute Grants EY-027257and EY-14801 (to SKB)an unrestricted grant to the University of Miami from Research to Prevent Blindness。
文摘Remyelination and need to access it:A range of diseases such as Guillain-Barre syndrome,Pelizaeus Merzbacher disease,relapsing-remitting and secondary progressive multiple sclerosis is associated with various degrees of nerve demyelination.These diseases present with various degrees of demyelination and differentclinical manifestations.
文摘We systematically study the evolution of modulated nerve impulses in a myelinated nerve fiber, where both the ionic current and membrane capacitance provide the necessary nonlinear feedbacks. This is achieved by using a perturbation technique, in which the Liénard form of the modified discrete Fitzhugh–Nagumo equation is reduced to the complex Ginzburg–Landau amplitude equation. Three distinct values of the capacitive feedback parameter are considered. At the critical value of the capacitive feedback parameter, it is shown that the dynamics of the system is governed by the dissipative nonlinear Schr?dinger equation. Linear stability analysis of the system depicts the instability of plane waves,which is manifested as burst of modulated nerve impulses that fulfills the Benjamin–Feir criteria. Variations of the capacitive feedback parameter generally influences the plane wave stability and hence the type of wave profile identified in the neural network. Results of numerical simulations mainly confirm the propagation, collision, and annihilation of nerve impulses in the myelinated axon.
基金supported by the Natural Science Foundation of Jiangsu Province of China,No.BK20171180(to XRW)
文摘Rosmarinic acid,a common ester extracted from Rosemary,Perilla frutescens,and Salvia miltiorrhiza Bunge,has been shown to have protective effects against various diseases.This is an investigation into whether rosmarinic acid can also affect the changes of white matter fibers and cognitive deficits caused by hypoxic injury.The right common carotid artery of 3-day-old rats was ligated for 2 hours.The rats were then prewarmed in a plastic container with holes in the lid,which was placed in 37°C water bath for 30 minutes.Afterwards,the rats were exposed to an atmosphere with 8% O2 and 92% N2 for 30 minutes to establish the perinatal hypoxia/ischemia injury models.The rat models were intraperitoneally injected with rosmarinic acid 20 mg/kg for 5 consecutive days.At 22 days after birth,rosmarinic acid was found to improve motor,anxiety,learning and spatial memory impairments induced by hypoxia/ischemia injury.Furthermore,rosmarinic acid promoted the proliferation of oligodendrocyte progenitor cells in the subventricular zone.After hypoxia/ischemia injury,rosmarinic acid reversed to some extent the downregulation of myelin basic protein and the loss of myelin sheath in the corpus callosum of white matter structure.Rosmarinic acid partially slowed down the expression of oligodendrocyte marker Olig2 and myelin basic protein and the increase of oligodendrocyte apoptosis marker inhibitors of DNA binding 2.These data indicate that rosmarinic acid ameliorated the cognitive dysfunction after perinatal hypoxia/ischemia injury by improving remyelination in corpus callosum.This study was approved by the Animal Experimental Ethics Committee of Xuzhou Medical University,China (approval No.20161636721) on September 16,2017.
基金supported by Multiple Sclerosis Society of Canada(MSSOC),No.2362(to VMKV)Canadian Institutes of Health Research(CIHR),No.14238(to VMKV)were supported by University of Saskatchewan College of Medicine Research Awards(Co MGRADs)。
文摘Our lab has shown that brief electrical nerve stimulation(ES)has a dramatic impact on remyelination of lysophosphatidyl choline(LPC)-induced focally demyelinated rat peripheral nerves,while also inducing an axon-protective phenotype and shifting macrophages from a predominantly pro-inflammatory toward a pro-repair phenotype.Whether this same potential exists in the central nervous system is not known.Thus,for proof of principle studies,the peripheral nerve demyelination and ES model was adapted to the central nervous system,whereby a unilateral focal LPC-induced demyelination of the dorsal column at the lumbar enlargement where the sciatic nerve afferents enter was created,so that subsequent ipsilateral sciatic nerve ES results in increased neural activity in the demyelinated axons.Data reveal a robust focal demyelination at 7 days post-LPC injection.Delivery of 1-hour ES at 7 days post-LPC polarizes macrophages/microglia toward a pro-repair phenotype when examined at 14 days post-LPC;results in smaller LPC-associated regions of inflammation compared to non-stimulated controls;results in significantly more cells of the oligodendroglial lineage in the demyelinated region;elevates myelin basic protein levels;and shifts the paranodal protein Caspr along demyelinated axons to a more restricted distribution,consistent with reformation of the paranodes of the nodes of Ranvier.ES also significantly enhanced levels of phosphorylated neurofilaments detected in the zones of demyelination,which has been shown to confer axon protection.Collectively these findings support that strategies that increase neural activity,such as brief electrical stimulation,can be beneficial for promoting intrinsic repair following focal demyelinating insults in demyelinating diseases such as multiple sclerosis.All animal procedures performed were approved by the University of Saskatchewan's Animal Research Ethics Board(protocol#20090087;last approval date:November 5,2020).
文摘BACKGROUND:Acupuncture treatment on injured cerebral axons has shown to provide efficacy in clinical practice.It is unknown whether acupuncture produces therapeutic effects by protecting injured cerebral myelin in ischemic stroke.OBJECTIVE:To test whether acupuncture provides protection for injured cerebral myelin,based on quantitative data from cerebral ischemia-reperfusion rats,and to compare the effects of early and late acupuncture on serum myelin basic protein(MBP) content and remyelination of the ischemic internal capsule.DESIGN,TIME AND SETTING:A randomized,controlled experiment was performed at the Neuro-biological Laboratory,Sichuan University from March 2005 to March 2006.MATERIALS:"Hua Tuo" Brand filiform needles were produced by the Medical Instrument Factory of Suzhou,China.METHODS:A total of 52 adult,healthy,male,Sprague Dawley rats were randomly assigned to four groups:control(n=4),model(n=16),early acupuncture(n=16),and late acupuncture(n=16).The focal cerebral ischemia-reperfusion model was established by middle cerebral artery occlusion in the right hemisphere using the modified thread embolism method in the latter three groups.Early and late acupuncture groups underwent acupuncture after ischemia for 30 minutes and 2 hours using the Xingnaokaiqiao needling method,respectively.Acupoints were "Neiguan"(PC 6) and "Sanyinjiao"(SP 6) on the bilateral sides,as well as "Shuigou"(DU 26) and "Baihui"(DU 20) with stimulation for 1 minute at each acupoint.Acupuncture at all acupoints was performed two or three times while the needle was retained,once per day.No special handling was administered to the control group.MAIN OUTCOME MEASURES:For each group,remyelination of the internal capsule was observed by Pal-Weigert's myelin staining and serum MBP content was detected using enzyme-linked immunosorbent assay method on days 1,3,5,and 7 following ischemia-reperfusion injury.RESULTS:Compared with the control group,massive demyelination of the internal capsule occurred,and serum MBP content increased in the model group(P<0.05).Compared with the model group,the extent of demyelination in the internal capsule was less distinct and serum MBP content was significantly less in the early and late acupuncture group(P<0.01).Compared with the late acupuncture group,serum MBP content reached a peak later and the peak value was less in the early acupuncture group.CONCLUSION:Results suggest that acupuncture exerts a protective effect on injured cerebral myelin in ischemia-reperfusion rats by reducing serum MBP content and promoting remyelination.The study also suggests that the effect of early acupuncture is superior to late acupuncture.
基金supported by the Deutsche Forschungsgemeinschaft(DFG,WE2720/2-2 and WE2720/4-1,both to HBW)
文摘Neural plasticity in the adult central nervous system involves the adaptation of myelination, including the formation of novel myelin sheaths by adult-born oligodendrocytes. Yet, mature oligodendrocytes slowly but constantly turn over their pre-existing myelin sheaths, thereby establishing an equilibrium of replenishment and degradation that may also be subject to adaptation with consequences for nerve conduction velocity. In this short review we highlight selected approaches to the normal turnover of adult myelin in vivo, from injecting radioactive precursors of myelin constituents in the 1960s to current strategies involving isotope labeling and tamoxifen-induced gene targeting.
文摘In this study, we investigated the clinical relevance of anti-myelin antibodies in patients with neuromyelitis optica (NMO);titers of antibodies against myelin oligodendrocyte glycoproteins, proteolipid proteins and myelin basic proteins were measured in the sera of patients with NMO and compared to healthy controls, as well as to patients with other diseases. The frequency of presence of anti-myelin antibodies in patients with NMO was significantly higher than that in healthy and diseased controls. The expanded disability status scale scores correlated with the titers of the anti-myelin antibodies. Patients with anti-myelin antibody exhibited other autoantibodies significantly more frequently than patients without the antibody. Anti-myelin antibodies may be useful markers for predicting severe clinical courses in patients with NMO.
文摘Since disability in multiple sclerosis(MS) is a product of neurodegeneration and deficient remyelination, the ability to enhance neuroregeneration and myelin regeneration in MS is an enticing goal for MS drug development. In particular, remyelination treatments could promote return of neurological function and also prevent further axonal loss and neurodegeneration in MS due to trophic effects of myelin. The study of remyelination has advanced dramatically in the last several years such that a number of pathways inhibiting remyelination have been discovered, including those involving LINGO-1, Notch-1, hyaluronan, retinoid X receptor, and wnt/?-catenin. Other approaches such as high throughput drug screening for remyelination drugs have caught fire, with identification of dozens of known drugs with oligodendrocyte maturation stimulatory effects. Several drugs identified through screens and other mechanisms are in the process of being further evaluated for remyelination in MS and MS models. We discuss the potential molecular targets and the variety of mechanisms towards drug identification and development in remyelination for MS.
基金supported by a grant of Guangdong Medical University of China,No.XB1380
文摘Salvianolic acid B,an active pharmaceutical compound present in Salvia miltiorrhiza,exerts a neuroprotective effect in animal models of brain and spinal cord injury.Salvianolic acid B can promote recovery of neurological function;however,its protective effect on the myelin sheath after spinal cord injury remains poorly understood.Thus,in this study,in vitro tests showed that salvianolic acid B contributed to oligodendrocyte precursor cell differentiation,and the most effective dose was 20 μg/m L.For in vivo investigation,rats with spinal cord injury were intraperitoneally injected with 20 mg/kg salvianolic acid B for 8 weeks.The amount of myelin sheath and the number of regenerating axons increased,neurological function recovered,and caspase-3 expression was decreased in the spinal cord of salvianolic acid B-treated animals compared with untreated control rats.These results indicate that salvianolic acid B can protect axons and the myelin sheath,and can promote the recovery of neurological function.Its mechanism of action is likely to be associated with inhibiting apoptosis and promoting the differentiation and maturation of oligodendrocyte precursor cells.
基金supported by grants from the National Institutes of Health(NS094151 and NS105689,both to WL)
文摘Activation of the unfolded protein response in response to endoplasmic reticulum stress preserves cell viability and function under stressful conditions.Nevertheless,persistent,unresolvable activation of the unfolded protein response can trigger apoptosis to eliminate stressed cells.Recent studies show that the unfolded protein response plays an important role in the pathogenesis of various disorders of myelin,including multiples sclerosis,Charcot-Marie-Tooth disease,Pelizaeus-Merzbacher disease,vanishing white matter disease,spinal cord injury,tuberous sclerosis complex,and hypoxia-induced perinatal white matter injury.In this review we summarize the current literature on the unfolded protein response and the evidence for its role in the pathogenesis of myelin disorders.
文摘AIM:To compare the thickness of the peripapillary retinal nerve fiber layer(RNFL)and ganglion cell-inner plexiform layer(GCIPL)among patients with various forms of optic neuritis(ON)and to identify whether any particular parameters or their thinning pattern can be used to distinguish the type of ON.METHODS:This prospective study was conducted at the Department of Ophthalmology,Faculty of Medicine,Siriraj Hospital,Thailand,between January,2015 and December,2016.We enlisted patients over 18 years of age with history of ON and categorized patients into 4 groups:1)aquaporin 4 antibodies(AQP4-IgG)positive;2)multiple sclerosis(MS);3)myelin oligodendrocyte glycoprotein antibodies(MOG-IgG)positive;4)idiopathic-ON patients.Healthy controls were also included during the same study period.All patients underwent complete ophthalmological examination and spectral domain optical coherence tomography(OCT)imaging to analyze RNFL and GCIPL thickness after at least 3mo since the last episode of acute ON.The generalized estimating equation(GEE)models were used to compare the data amongst ON groups. RESULTS: Among 87 previous ON eyes from 57 patients(43 AQP4-IgG+ON,17 MS-ON,8 MOG-IgG+ON,and 19idiopathic-ON),mean logMAR visual acuity of AQP4-IgG+ON,MS-ON,MOG-IgG+ON,and idiopathic-ON groups was 0.76±0.88,0.12±0.25,0.39±0.31,and 0.75±1.08,respectively.Average,superior,and inferior RNFL were significantly reduced in AQP4-IgG+ON,MOG-IgG+ON and idiopathic-ON eyes,relative to those of MS-ON.Differences were not statistically significant for RNFL or GCIPL between the AQP4-IgG+ON and MOG-IgG+ON groups,whereas visual acuity in MOG-IgG+ON was slightly,but not significantly,better(0.39 vs 0.76).Although RNFL thickness in MOG-IgG+ON was significantly reduced as compared to MS-ON,mean visual acuity and GCIPL were not different.CONCLUSION:Thinning of superior and inferior quadrants of RNFL are more commonly seen in MOG-IgG+ON and AQP4-IgG+ON.Long term visual acuity in MOG-IgG+ON is often better than AQP4-IgG+ON,whereas the structural change from OCT is comparable.
文摘Multiple sclerosis(MS)is a neurodegenerative disease characterized by inflammation and demyelination.Studies are focused on encountering remyelination therapies that can be applied to delaying,or even decreasing,the motor and cognitive disabilities caused by the disease.The cellular/molecular changes in MS are dynamic,with inflammation,demyelination and remyelination inducing progressive neurodegenerative changes in the central nervous system,as a whole.Moreover,the imaging methods for accompanying the process are,as yet,shortcoming.
