Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotectiv...Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined.In this study,we established rat models of spinal cord injury by modified Allen’s method and intraperitoneally administered 1000 and 5000 IU/kg erythropoietin once a week for 2 successive weeks.Both low and high doses of erythropoietin promoted recovery of hindlimb function,and the high dose of erythropoietin led to better outcome.High dose of erythropoietin exhibited a stronger suppressive effect on ferroptosis relative to the low dose of erythropoietin.The effects of erythropoietin on inhibiting ferroptosis-related protein expression and restoring mitochondrial morphology were similar to those of Fer-1(a ferroptosis suppressor),and the effects of erythropoietin were largely diminished by RSL3(ferroptosis activator).In vitro experiments showed that erythropoietin inhibited RSL3-induced ferroptosis in PC12 cells and increased the expression of xCT and Gpx4.This suggests that xCT and Gpx4 are involved in the neuroprotective effects of erythropoietin on spinal cord injury.Our findings reveal the underlying anti-ferroptosis role of erythropoietin and provide a potential therapeutic strategy for treating spinal cord injury.展开更多
Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promo...Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model,while its effect on ischemic stroke remains elusive.In this study,we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell prolife ration and enhanced angiogenesis.In rat models of focal cerebral ischemia,ove rexpression of miR-181b reduced infarction volume,promoted angiogenesis in ischemic penumbra,and improved neurological function.We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3’-UTR of phosphatase and tensin homolog(PTEN) mRNA to induce PTEN downregulation,leading to activation of the protein kinase B(Akt) pathway,upregulated expression of vascular endothelial growth facto rs,down-regulated expression of endostatin,and promoted angiogenesis.Taken togethe r,these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stro ke through activating the PTEN/Akt signal pathway and promoting angiogenesis.展开更多
T cells are essential for a healthy life,performing continuously:immune surveillance,recognition,protection,activation,suppression,assistance,eradication,secretion,adhesion,migration,homing,communications,and addition...T cells are essential for a healthy life,performing continuously:immune surveillance,recognition,protection,activation,suppression,assistance,eradication,secretion,adhesion,migration,homing,communications,and additional tasks.This paper describes five aspects of normal beneficial T cells in the healthy or diseased brain.First,normal beneficial T cells are essential for normal healthy brain functions:cognition,spatial learning,memory,adult neurogenesis,and neuroprotection.T cells decrease secondary neuronal degeneration,increase neuronal survival after central nervous system(CNS) injury,and limit CNS inflammation and damage upon injury and infection.Second,while pathogenic T cells contribute to CNS disorders,recent studies,mostly in animal models,show that specific subpopulations of normal beneficial T cells have protective and regenerative effects in seve ral neuroinflammatory and neurodegenerative diseases.These include M ultiple Sclerosis(MS),Alzheimer’s disease,Parkinson’s disease,Amyotrophic Lateral Sclerosis(ALS),stro ke,CNS trauma,chronic pain,and others.Both T cell-secreted molecules and direct cell-cell contacts deliver T cell neuroprotective,neuro regenerative and immunomodulato ry effects.Third,normal beneficial T cells are abnormal,impaired,and dysfunctional in aging and multiple neurological diseases.Different T cell impairments are evident in aging,brain tumors(mainly Glioblastoma),seve re viral infections(including COVID-19),chro nic stress,major depression,schizophrenia,Parkinson’s disease,Alzheimer’s disease,ALS,MS,stro ke,and other neuro-pathologies.The main detrimental mechanisms that impair T cell function are activation-induced cell death,exhaustion,senescence,and impaired T cell stemness.Fo urth,several physiological neurotransmitters and neuro peptides induce by themselves multiple direct,potent,beneficial,and therapeutically-relevant effects on normal human T cells,via their receptors in T cells.This scientific field is called "Nerve-Driven Immunity".The main neurotransmitters and neuropeptides that induce directly activating and beneficial effects on naive normal human T cells are:dopamine,glutamate,GnRH-Ⅱ,neuropeptide Y,calcitonin gene-related peptide,and somatostatin.Fifth, "Personalized Adoptive Neuro-Immunotherapy".This is a novel unique cellular immunotherapy,based on the "Nerve-Driven Immunity" findings,which was recently designed and patented for safe and repeated rejuvenation,activation,and improvement of impaired and dysfunctional T cells of any person in need,by ex vivo exposure of the person’s T cells to neurotransmitters and neuropeptides.Personalized adoptive neuro-immunotherapy includes an early ex vivo personalized diagnosis,and subsequent ex vivo in vivo personalized adoptive therapy,tailo red according to the diagnosis.The Personalized Adoptive Neuro-Immunotherapy has not yet been tested in humans,pending validation of safety and efficacy in clinical trials,especially in brain tumors,chronic infectious diseases,and aging,in which T cells are exhausted and/or senescent and dysfunctional.展开更多
Studies have shown that repetitive transcra nial magnetic stimulation(rTMS)can enhance synaptic plasticity and improve neurological dysfunction.Howeve r,the mechanism through which rTMS can improve moderate traumatic ...Studies have shown that repetitive transcra nial magnetic stimulation(rTMS)can enhance synaptic plasticity and improve neurological dysfunction.Howeve r,the mechanism through which rTMS can improve moderate traumatic brain injury remains poorly understood.In this study,we established rat models of moderate traumatic brain injury using Feeney's weight-dropping method and treated them using rTMS.To help determine the mechanism of action,we measured levels of seve ral impo rtant brain activity-related proteins and their mRNA.On the injured side of the brain,we found that rTMS increased the protein levels and mRNA expression of brain-derived neurotrophic factor,tropomyosin receptor kinase B,N-methyl-D-aspartic acid receptor 1,and phosphorylated cAMP response element binding protein,which are closely associated with the occurrence of long-term potentiation.rTMS also partially reve rsed the loss of synaptophysin after injury and promoted the remodeling of synaptic ultrastructure.These findings suggest that upregulation of synaptic plasticity-related protein expression is the mechanism through which rTMS promotes neurological function recovery after moderate traumatic brain injury.展开更多
BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a the...BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease.AIM To investigate the effect of ganglioside(GM)combined with methylprednisolone sodium succinate(MPSS)on the curative effect and neurological function of patients with AM.METHODS First,we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality,with 52 patients receiving gamma globulin(GG)+MPSS and 56 patients receiving GM+MPSS,assigned to the control group(Con)and observation group(Obs),respectively.The therapeutic effect,neurological function(sensory and motor function scores),adverse events(AEs),recovery(time to sphincter function recovery,time to limb muscle strength recovery above grade 2,and time to ambulation),inflammatory factors(IFs)[interleukin(IL)-6,C-reactive protein(CRP),and tumor necrosis factor(TNF)-α]and other data of the two groups were collected for evaluation and comparison.RESULTS The Obs had:(1)A significantly higher response rate of treatment than the Con;(2)Higher scores of sensory and motor functions after treatment that were higher than the baseline(before treatment)and higher than the Con levels;(3)Lower incidence rates of skin rash,gastrointestinal discomfort,dyslipidemia,osteoporosis and other AEs;(4)Faster posttreatment recovery of sphincter function,limb muscle strength and ambulation;and(5)Markedly lower posttreatment IL-6,CRP and TNF-αlevels than the baseline and the Con levels.CONCLUSION From the above,it can be seen that GM+MPSS is highly effective in treating AM,with a favorable safety profile comparable to that of GG+MPSS.It can significantly improve patients’neurological function,speed up their recovery and inhibit serum IFs.展开更多
BACKGROUND We report a rare case of full neurological recovery from severe nonexertional heat stroke in a 67-year-old woman with an initial Glasgow Coma Scale of 3.This report raises awareness among doctors that when ...BACKGROUND We report a rare case of full neurological recovery from severe nonexertional heat stroke in a 67-year-old woman with an initial Glasgow Coma Scale of 3.This report raises awareness among doctors that when heatstroke is diagnosed,comprehensive treatment should be implemented as soon as possible.Moreover,targeted temperature management,combination therapy with hemodialysis and hemoperfusion,and hyperbaric oxygen therapy may alleviate multiorgan failure and prevent neurological sequelae caused by heatstroke.CASE SUMMARY A previously healthy 67-year-old woman with an initial Glasgow Coma Scale of 3 was found lying prone on the road at noon on a summer day.Laboratory tests revealed multiorgan failure.As soon as heatstroke was diagnosed,comprehensive treatment was implemented.On hospital Day 3,the patient was extubated.Her initial Sequential Organ Failure Assessment score at hospitalization was 14 and decreased to 2 on hospital Day 4.On the seventh day following hospital admission,as the patient’s general condition improved,the levels of laboratory test findings decreased rapidly.Finally,the patient gradually recovered with no other neurological symptoms(the Glasgow Coma Scale at discharge was 15,and her ability to walk independently was restored).CONCLUSION This case demonstrated that targeted temperature management,combination therapy with hemodialysis and hemoperfusion,and hyperbaric oxygen therapy may alleviate multiorgan failure and prevent neurological sequelae caused by heatstroke.展开更多
The process of entrainment-mixing between cumulus clouds and the ambient air is important for the development of cumulus clouds.Accurately obtaining the entrainment rate(λ)is particularly important for its parameteri...The process of entrainment-mixing between cumulus clouds and the ambient air is important for the development of cumulus clouds.Accurately obtaining the entrainment rate(λ)is particularly important for its parameterization within the overall cumulus parameterization scheme.In this study,an improved bulk-plume method is proposed by solving the equations of two conserved variables simultaneously to calculateλof cumulus clouds in a large-eddy simulation.The results demonstrate that the improved bulk-plume method is more reliable than the traditional bulk-plume method,becauseλ,as calculated from the improved method,falls within the range ofλvalues obtained from the traditional method using different conserved variables.The probability density functions ofλfor all data,different times,and different heights can be well-fitted by a log-normal distribution,which supports the assumed stochastic entrainment process in previous studies.Further analysis demonstrate that the relationship betweenλand the vertical velocity is better than other thermodynamic/dynamical properties;thus,the vertical velocity is recommended as the primary influencing factor for the parameterization ofλin the future.The results of this study enhance the theoretical understanding ofλand its influencing factors and shed new light on the development ofλparameterization.展开更多
Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^...Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell membrane.Na^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of cells.Therefo re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological diseases.However,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell function.Our recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's disease.Stabilization of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these diseases.For this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell migration.Thus,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related pathogenesis.The potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.展开更多
Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks,which have been widely applied in the field of central neurological diseases,such as stroke,Parkinson...Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks,which have been widely applied in the field of central neurological diseases,such as stroke,Parkinson’s disease,and mental disorders.Although significant advances have been made in neuromodulation technologies,the identification of optimal neurostimulation paramete rs including the co rtical target,duration,and inhibition or excitation pattern is still limited due to the lack of guidance for neural circuits.Moreove r,the neural mechanism unde rlying neuromodulation for improved behavioral performance remains poorly understood.Recently,advancements in neuroimaging have provided insight into neuromodulation techniques.Functional near-infrared spectroscopy,as a novel non-invasive optical brain imaging method,can detect brain activity by measuring cerebral hemodynamics with the advantages of portability,high motion tole rance,and anti-electromagnetic interference.Coupling functional near-infra red spectroscopy with neuromodulation technologies offe rs an opportunity to monitor the cortical response,provide realtime feedbac k,and establish a closed-loop strategy integrating evaluation,feedbac k,and intervention for neurostimulation,which provides a theoretical basis for development of individualized precise neuro rehabilitation.We aimed to summarize the advantages of functional near-infra red spectroscopy and provide an ove rview of the current research on functional near-infrared spectroscopy in transcranial magnetic stimulation,transcranial electrical stimulation,neurofeedback,and braincomputer interfaces.Furthermore,the future perspectives and directions for the application of functional near-infrared spectroscopy in neuromodulation are summarized.In conclusion,functional near-infrared spectroscopy combined with neuromodulation may promote the optimization of central pellral reorganization to achieve better functional recovery form central nervous system diseases.展开更多
Since the early stages of life on earth,cellular metabolism has evolved to adapt to fluctuations in nutrient and oxygen availability.In this context,mammals,which are probably the organisms that show one of the highes...Since the early stages of life on earth,cellular metabolism has evolved to adapt to fluctuations in nutrient and oxygen availability.In this context,mammals,which are probably the organisms that show one of the highest levels of metabolic complexity,have developed an elegant system that uses constant and rechargeable energy sources of modulate their metabolism.This homeostasis is especially important in the central nervous system,as neurons and other cells in the brain are highly susceptible to fluctuations in nutrients and oxygen availability.展开更多
Microglia are one of the three glial cell populations in the central nervous system(CNS),along with astrocytes and oligodendrocytes.While microglia are unique among brain cells due to their hematologic origin and perf...Microglia are one of the three glial cell populations in the central nervous system(CNS),along with astrocytes and oligodendrocytes.While microglia are unique among brain cells due to their hematologic origin and perform immune functions similar to peripheral macrophages,they are not simply macrophages of the CNS.展开更多
Astrocytes are the most abundant glial cells in the central nervous system;they participate in crucial biological processes,maintain brain structure,and regulate nervous system function.Exosomes are cell-derived extra...Astrocytes are the most abundant glial cells in the central nervous system;they participate in crucial biological processes,maintain brain structure,and regulate nervous system function.Exosomes are cell-derived extracellular vesicles containing various bioactive molecules including proteins,peptides,nucleotides,and lipids secreted from their cellular sources.Increasing evidence shows that exosomes participate in a communication network in the nervous system,in which astrocyte-derived exosomes play important roles.In this review,we have summarized the effects of exosomes targeting astrocytes and the astrocyte-derived exosomes targeting other cell types in the central nervous system.We also discuss the potential research directions of the exosome-based communication network in the nervous system.The exosome-based intercellular communication focused on astrocytes is of great significance to the biological and/or pathological processes in different conditions in the brain.New strategies may be developed for the diagnosis and treatment of neurological disorders by focusing on astrocytes as the central cells and utilizing exosomes as communication mediators.展开更多
Glycosylation is a process that involves the addition of sugar moieties or glycans to different types of molecules,including proteins,lipids,and nucleic acids.Among these,protein glycosylation is one of the most preva...Glycosylation is a process that involves the addition of sugar moieties or glycans to different types of molecules,including proteins,lipids,and nucleic acids.Among these,protein glycosylation is one of the most prevalent forms of post-translational modification,playing a crucial role in biological complexity.With more than ten monosaccharides identified within mammalian brain cells and more than 1×1012 possible combinations,the heterogeneity of glycosylation is extensive(Conroy et al.,2021).The diversity of glycans and the complexity of their structures allow for a wide range of protein functions.N-glycans are one of the most abundant forms of glycans and are involved in various cellular functions.N-glycans can be added to proteins at specific sequons,Asn-X-Ser/Thr,and are classified into three main types in mature glycoproteins:high mannose,complex,and hybrid.High mannose N-glycans consist of 5-9 mannose residues linked to a chitobiose core and undergo processing into complex or hybrid forms in the Golgi apparatus(Varki et al.,2017).Complex N-glycans are more diverse and contain various branched structures such as antennae with fucose,galactose,and sialic acid residues.Hybrid N-glycans contain one or more complex branches in conjunction with an oligomannose branch(Fisher and Ungar,2016).Understanding the specific functions of these different types of N-glycans in protein regulation,folding,and function is an active area of research in the life sciences,including glycobiology.展开更多
Background:Excessive heat exposure can lead to hyperthermia in humans,which impairs physical performance and disrupts cognitive function.While heat is a known physiological stressor,it is unclear how severe heat stres...Background:Excessive heat exposure can lead to hyperthermia in humans,which impairs physical performance and disrupts cognitive function.While heat is a known physiological stressor,it is unclear how severe heat stress affects brain physiology and function.Methods:Eleven healthy participants were subjected to heat stress from prolonged exercise or warm water immersion until their rectal temperatures(T_(re))attained 39.5℃,inducing exertional or passive hyperthermia,respectively.In a separate trial,blended ice was ingested before and during exercise as a cooling strategy.Data were compared to a control condition with seated rest(normothermic).Brain temperature(T_(br)),cerebral perfusion,and task-based brain activity were assessed using magnetic resonance imaging techniques.Results:T_(br)in motor cortex was found to be tightly regulated at rest(37.3℃±0.4℃(mean±SD))despite fluctuations in T_(re).With the development of hyperthermia,T_(br)increases and dovetails with the rising T_(re).Bilateral motor cortical activity was suppressed during high-intensity plantarflexion tasks,implying a reduced central motor drive in hyperthermic participants(T_(re)=38.5℃±0.1℃).Global gray matter perfusion and regional perfusion in sensorimotor cortex were reduced with passive hyperthermia.Executive function was poorer under a passive hyperthermic state,and this could relate to compromised visual processing as indicated by the reduced activation of left lateral-occipital cortex.Conversely,ingestion of blended ice before and during exercise alleviated the rise in both T_(re)and T_(bc)and mitigated heat-related neural perturbations.Conclusion:Severe heat exposure elevates T_(br),disrupts motor cortical activity and executive function,and this can lead to impairment of physical and cognitive performance.展开更多
The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding protein.As the largest member...The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding protein.As the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent protein.Although many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its discovery.In this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder itself.Additionally,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of study.This review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.展开更多
Our brain is constantly active.Even at rest,the brain carries out essential functions such as maintenance of resting potentials,subthreshold synaptic activity,and spiking activity related to information processing.Thi...Our brain is constantly active.Even at rest,the brain carries out essential functions such as maintenance of resting potentials,subthreshold synaptic activity,and spiking activity related to information processing.This resting activity can be assessed with several in vivo tools,such as resting-state functional magnetic resonance imaging.This technique measures subtle changes in blood flow,volume,and oxygenation that occur over time.Although vascular in nature,resting-state functional magnetic resonance imaging is considered a reliable proxy of neural activity and several studies have shown that the brain is functionally divided into interacting neural networks called the“functional connectome”.展开更多
Functional magnetic resonance imaging(fMRI)is a popular tool used to investigate not only how the brain responds to specific stimuli during sensorimotor or cognitive tasks,but also brain activity at rest.The physics b...Functional magnetic resonance imaging(fMRI)is a popular tool used to investigate not only how the brain responds to specific stimuli during sensorimotor or cognitive tasks,but also brain activity at rest.The physics beyond this approach is based on the analysis of the blood oxygenation level-dependent signal.展开更多
With the increase of life expectancy and population growth,neurodegenerative diseases have risen too and are projected to be a major health public concern by 2050.Neurodegenerative diseases are characterized by the pr...With the increase of life expectancy and population growth,neurodegenerative diseases have risen too and are projected to be a major health public concern by 2050.Neurodegenerative diseases are characterized by the progressive decline of cognitive function leading to the subsequent loss of autonomy.Although the underlying causes of neurodegeneration are not well understood,aging is the main risk factor.展开更多
The authors report a case of deficient sensory neuropathy secondary to vitamin B12 deficiency, diagnosed in the neurology department of the Sino-Central African Friendship University Hospital in Bangui. The diagnosis ...The authors report a case of deficient sensory neuropathy secondary to vitamin B12 deficiency, diagnosed in the neurology department of the Sino-Central African Friendship University Hospital in Bangui. The diagnosis was made possible by electroneuromyography which showed subclinical neurological damage associated with hematological damage (anemia). Through this observation, we recall the diagnostic criteria of the disease in a context of difficult medical practice. .展开更多
The implementation of Ecological Function Protection Zone(EFPZ)policy is significant for the ecological restoration and conservation of soil and water in the territory space.This manuscript analyzed and quantified the...The implementation of Ecological Function Protection Zone(EFPZ)policy is significant for the ecological restoration and conservation of soil and water in the territory space.This manuscript analyzed and quantified the impact of EFPZ on the regional water conservation function,based on land use data from 2005,2008,2010,2015 and 2020,by conducting a counterfactual simulation along with the GeoSOS-FLUS model and the InVEST model.The results demonstrate that the delineation of EFPZ can significantly influence the water conservation.(1)From 2010 to 2020,as the EFPZ was implemented,the water conservation in the study area was increasing year by year,with a growth rate of 0.03×10^(8) m^(3)∙a^(-1).On the other hand,the simulated water conservation capacity without the implementation of EFPZ decreased year by year,with a decrease rate of 0.01×10^(8) m^(3)∙a^(-1).(2)The EFPZ accounts for only 23%of the total area,but the contribution rate of water conservation reaches 80%.The actual values of water conservation and average water yield per unit pixel in the EFPZ show an increasing trend both internally and externally,while the counterfactual simulation values exhibit a decreasing trend.(3)The water conservation is much higher within the EFPZ than without EFPZ.The implementation of EFPZ has a significant effect on the improvement of the water conservation capacity in Maqu EFPZ and Yellow River Source EFPZ.The protection effectiveness should be enhanced in Qilian Mountain EFPZ and afforestation activities need to be carefully considered in Loess Plateau EFPZ.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81871785 and 81672161(both to ZSY)。
文摘Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined.In this study,we established rat models of spinal cord injury by modified Allen’s method and intraperitoneally administered 1000 and 5000 IU/kg erythropoietin once a week for 2 successive weeks.Both low and high doses of erythropoietin promoted recovery of hindlimb function,and the high dose of erythropoietin led to better outcome.High dose of erythropoietin exhibited a stronger suppressive effect on ferroptosis relative to the low dose of erythropoietin.The effects of erythropoietin on inhibiting ferroptosis-related protein expression and restoring mitochondrial morphology were similar to those of Fer-1(a ferroptosis suppressor),and the effects of erythropoietin were largely diminished by RSL3(ferroptosis activator).In vitro experiments showed that erythropoietin inhibited RSL3-induced ferroptosis in PC12 cells and increased the expression of xCT and Gpx4.This suggests that xCT and Gpx4 are involved in the neuroprotective effects of erythropoietin on spinal cord injury.Our findings reveal the underlying anti-ferroptosis role of erythropoietin and provide a potential therapeutic strategy for treating spinal cord injury.
基金supported by the National Natural Science Foundation of China,Nos.81801169 (to LXX),82071404 (to HC),81870952 (to HMW)。
文摘Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model,while its effect on ischemic stroke remains elusive.In this study,we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell prolife ration and enhanced angiogenesis.In rat models of focal cerebral ischemia,ove rexpression of miR-181b reduced infarction volume,promoted angiogenesis in ischemic penumbra,and improved neurological function.We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3’-UTR of phosphatase and tensin homolog(PTEN) mRNA to induce PTEN downregulation,leading to activation of the protein kinase B(Akt) pathway,upregulated expression of vascular endothelial growth facto rs,down-regulated expression of endostatin,and promoted angiogenesis.Taken togethe r,these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stro ke through activating the PTEN/Akt signal pathway and promoting angiogenesis.
文摘T cells are essential for a healthy life,performing continuously:immune surveillance,recognition,protection,activation,suppression,assistance,eradication,secretion,adhesion,migration,homing,communications,and additional tasks.This paper describes five aspects of normal beneficial T cells in the healthy or diseased brain.First,normal beneficial T cells are essential for normal healthy brain functions:cognition,spatial learning,memory,adult neurogenesis,and neuroprotection.T cells decrease secondary neuronal degeneration,increase neuronal survival after central nervous system(CNS) injury,and limit CNS inflammation and damage upon injury and infection.Second,while pathogenic T cells contribute to CNS disorders,recent studies,mostly in animal models,show that specific subpopulations of normal beneficial T cells have protective and regenerative effects in seve ral neuroinflammatory and neurodegenerative diseases.These include M ultiple Sclerosis(MS),Alzheimer’s disease,Parkinson’s disease,Amyotrophic Lateral Sclerosis(ALS),stro ke,CNS trauma,chronic pain,and others.Both T cell-secreted molecules and direct cell-cell contacts deliver T cell neuroprotective,neuro regenerative and immunomodulato ry effects.Third,normal beneficial T cells are abnormal,impaired,and dysfunctional in aging and multiple neurological diseases.Different T cell impairments are evident in aging,brain tumors(mainly Glioblastoma),seve re viral infections(including COVID-19),chro nic stress,major depression,schizophrenia,Parkinson’s disease,Alzheimer’s disease,ALS,MS,stro ke,and other neuro-pathologies.The main detrimental mechanisms that impair T cell function are activation-induced cell death,exhaustion,senescence,and impaired T cell stemness.Fo urth,several physiological neurotransmitters and neuro peptides induce by themselves multiple direct,potent,beneficial,and therapeutically-relevant effects on normal human T cells,via their receptors in T cells.This scientific field is called "Nerve-Driven Immunity".The main neurotransmitters and neuropeptides that induce directly activating and beneficial effects on naive normal human T cells are:dopamine,glutamate,GnRH-Ⅱ,neuropeptide Y,calcitonin gene-related peptide,and somatostatin.Fifth, "Personalized Adoptive Neuro-Immunotherapy".This is a novel unique cellular immunotherapy,based on the "Nerve-Driven Immunity" findings,which was recently designed and patented for safe and repeated rejuvenation,activation,and improvement of impaired and dysfunctional T cells of any person in need,by ex vivo exposure of the person’s T cells to neurotransmitters and neuropeptides.Personalized adoptive neuro-immunotherapy includes an early ex vivo personalized diagnosis,and subsequent ex vivo in vivo personalized adoptive therapy,tailo red according to the diagnosis.The Personalized Adoptive Neuro-Immunotherapy has not yet been tested in humans,pending validation of safety and efficacy in clinical trials,especially in brain tumors,chronic infectious diseases,and aging,in which T cells are exhausted and/or senescent and dysfunctional.
基金supported by the President Foundation of Nanfang Hospital,Southern Medical University,No.2016Z003(50107021)(to JZF).
文摘Studies have shown that repetitive transcra nial magnetic stimulation(rTMS)can enhance synaptic plasticity and improve neurological dysfunction.Howeve r,the mechanism through which rTMS can improve moderate traumatic brain injury remains poorly understood.In this study,we established rat models of moderate traumatic brain injury using Feeney's weight-dropping method and treated them using rTMS.To help determine the mechanism of action,we measured levels of seve ral impo rtant brain activity-related proteins and their mRNA.On the injured side of the brain,we found that rTMS increased the protein levels and mRNA expression of brain-derived neurotrophic factor,tropomyosin receptor kinase B,N-methyl-D-aspartic acid receptor 1,and phosphorylated cAMP response element binding protein,which are closely associated with the occurrence of long-term potentiation.rTMS also partially reve rsed the loss of synaptophysin after injury and promoted the remodeling of synaptic ultrastructure.These findings suggest that upregulation of synaptic plasticity-related protein expression is the mechanism through which rTMS promotes neurological function recovery after moderate traumatic brain injury.
基金This study was approved by the Ethic Committee of Basic Medical College of Qingdao University(Approval No.QDWMkj-2020-012).
文摘BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease.AIM To investigate the effect of ganglioside(GM)combined with methylprednisolone sodium succinate(MPSS)on the curative effect and neurological function of patients with AM.METHODS First,we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality,with 52 patients receiving gamma globulin(GG)+MPSS and 56 patients receiving GM+MPSS,assigned to the control group(Con)and observation group(Obs),respectively.The therapeutic effect,neurological function(sensory and motor function scores),adverse events(AEs),recovery(time to sphincter function recovery,time to limb muscle strength recovery above grade 2,and time to ambulation),inflammatory factors(IFs)[interleukin(IL)-6,C-reactive protein(CRP),and tumor necrosis factor(TNF)-α]and other data of the two groups were collected for evaluation and comparison.RESULTS The Obs had:(1)A significantly higher response rate of treatment than the Con;(2)Higher scores of sensory and motor functions after treatment that were higher than the baseline(before treatment)and higher than the Con levels;(3)Lower incidence rates of skin rash,gastrointestinal discomfort,dyslipidemia,osteoporosis and other AEs;(4)Faster posttreatment recovery of sphincter function,limb muscle strength and ambulation;and(5)Markedly lower posttreatment IL-6,CRP and TNF-αlevels than the baseline and the Con levels.CONCLUSION From the above,it can be seen that GM+MPSS is highly effective in treating AM,with a favorable safety profile comparable to that of GG+MPSS.It can significantly improve patients’neurological function,speed up their recovery and inhibit serum IFs.
文摘BACKGROUND We report a rare case of full neurological recovery from severe nonexertional heat stroke in a 67-year-old woman with an initial Glasgow Coma Scale of 3.This report raises awareness among doctors that when heatstroke is diagnosed,comprehensive treatment should be implemented as soon as possible.Moreover,targeted temperature management,combination therapy with hemodialysis and hemoperfusion,and hyperbaric oxygen therapy may alleviate multiorgan failure and prevent neurological sequelae caused by heatstroke.CASE SUMMARY A previously healthy 67-year-old woman with an initial Glasgow Coma Scale of 3 was found lying prone on the road at noon on a summer day.Laboratory tests revealed multiorgan failure.As soon as heatstroke was diagnosed,comprehensive treatment was implemented.On hospital Day 3,the patient was extubated.Her initial Sequential Organ Failure Assessment score at hospitalization was 14 and decreased to 2 on hospital Day 4.On the seventh day following hospital admission,as the patient’s general condition improved,the levels of laboratory test findings decreased rapidly.Finally,the patient gradually recovered with no other neurological symptoms(the Glasgow Coma Scale at discharge was 15,and her ability to walk independently was restored).CONCLUSION This case demonstrated that targeted temperature management,combination therapy with hemodialysis and hemoperfusion,and hyperbaric oxygen therapy may alleviate multiorgan failure and prevent neurological sequelae caused by heatstroke.
基金supported by the National Natural Science Foundation of China(Grant Nos.42175099,42027804,42075073)the Innovative Project of Postgraduates in Jiangsu Province in 2023(Grant No.KYCX23_1319)+3 种基金supported by the National Natural Science Foundation of China(Grant No.42205080)the Natural Science Foundation of Sichuan(Grant No.2023YFS0442)the Research Fund of Civil Aviation Flight University of China(Grant No.J2022-037)supported by the National Key Scientific and Technological Infrastructure project“Earth System Science Numerical Simulator Facility”(Earth Lab)。
文摘The process of entrainment-mixing between cumulus clouds and the ambient air is important for the development of cumulus clouds.Accurately obtaining the entrainment rate(λ)is particularly important for its parameterization within the overall cumulus parameterization scheme.In this study,an improved bulk-plume method is proposed by solving the equations of two conserved variables simultaneously to calculateλof cumulus clouds in a large-eddy simulation.The results demonstrate that the improved bulk-plume method is more reliable than the traditional bulk-plume method,becauseλ,as calculated from the improved method,falls within the range ofλvalues obtained from the traditional method using different conserved variables.The probability density functions ofλfor all data,different times,and different heights can be well-fitted by a log-normal distribution,which supports the assumed stochastic entrainment process in previous studies.Further analysis demonstrate that the relationship betweenλand the vertical velocity is better than other thermodynamic/dynamical properties;thus,the vertical velocity is recommended as the primary influencing factor for the parameterization ofλin the future.The results of this study enhance the theoretical understanding ofλand its influencing factors and shed new light on the development ofλparameterization.
基金supported by the National Natural Science Foundation of China,No.82173800 (to JB)Shenzhen Science and Technology Program,No.KQTD20200820113040070 (to JB)。
文摘Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell membrane.Na^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of cells.Therefo re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological diseases.However,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell function.Our recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's disease.Stabilization of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these diseases.For this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell migration.Thus,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related pathogenesis.The potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.
文摘Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks,which have been widely applied in the field of central neurological diseases,such as stroke,Parkinson’s disease,and mental disorders.Although significant advances have been made in neuromodulation technologies,the identification of optimal neurostimulation paramete rs including the co rtical target,duration,and inhibition or excitation pattern is still limited due to the lack of guidance for neural circuits.Moreove r,the neural mechanism unde rlying neuromodulation for improved behavioral performance remains poorly understood.Recently,advancements in neuroimaging have provided insight into neuromodulation techniques.Functional near-infrared spectroscopy,as a novel non-invasive optical brain imaging method,can detect brain activity by measuring cerebral hemodynamics with the advantages of portability,high motion tole rance,and anti-electromagnetic interference.Coupling functional near-infra red spectroscopy with neuromodulation technologies offe rs an opportunity to monitor the cortical response,provide realtime feedbac k,and establish a closed-loop strategy integrating evaluation,feedbac k,and intervention for neurostimulation,which provides a theoretical basis for development of individualized precise neuro rehabilitation.We aimed to summarize the advantages of functional near-infra red spectroscopy and provide an ove rview of the current research on functional near-infrared spectroscopy in transcranial magnetic stimulation,transcranial electrical stimulation,neurofeedback,and braincomputer interfaces.Furthermore,the future perspectives and directions for the application of functional near-infrared spectroscopy in neuromodulation are summarized.In conclusion,functional near-infrared spectroscopy combined with neuromodulation may promote the optimization of central pellral reorganization to achieve better functional recovery form central nervous system diseases.
基金RTDC postdoctoral fellowship is defrayed by an AHA Supplement to Promote Diversity in Science.MES is funded by AHA(Career Development Award),Rutgers University(StartUp Funds),and NIH(R00AG055701).
文摘Since the early stages of life on earth,cellular metabolism has evolved to adapt to fluctuations in nutrient and oxygen availability.In this context,mammals,which are probably the organisms that show one of the highest levels of metabolic complexity,have developed an elegant system that uses constant and rechargeable energy sources of modulate their metabolism.This homeostasis is especially important in the central nervous system,as neurons and other cells in the brain are highly susceptible to fluctuations in nutrients and oxygen availability.
文摘Microglia are one of the three glial cell populations in the central nervous system(CNS),along with astrocytes and oligodendrocytes.While microglia are unique among brain cells due to their hematologic origin and perform immune functions similar to peripheral macrophages,they are not simply macrophages of the CNS.
基金supported by the National Natural Science Foundation of China,No.82071278(to PY)Outstanding Young Medical Talents Project of Changhai Hospital,No.2021JCSQ03(to PY)+1 种基金Shanghai Sailing Program,No.20YF1448000(to XZ)Medical Health Science and Technology Project of Zhoushan City,No.2022JRC01(to HL).
文摘Astrocytes are the most abundant glial cells in the central nervous system;they participate in crucial biological processes,maintain brain structure,and regulate nervous system function.Exosomes are cell-derived extracellular vesicles containing various bioactive molecules including proteins,peptides,nucleotides,and lipids secreted from their cellular sources.Increasing evidence shows that exosomes participate in a communication network in the nervous system,in which astrocyte-derived exosomes play important roles.In this review,we have summarized the effects of exosomes targeting astrocytes and the astrocyte-derived exosomes targeting other cell types in the central nervous system.We also discuss the potential research directions of the exosome-based communication network in the nervous system.The exosome-based intercellular communication focused on astrocytes is of great significance to the biological and/or pathological processes in different conditions in the brain.New strategies may be developed for the diagnosis and treatment of neurological disorders by focusing on astrocytes as the central cells and utilizing exosomes as communication mediators.
基金supported by the Institute for Basic Science(IBS-R001-D2-2022-A03).
文摘Glycosylation is a process that involves the addition of sugar moieties or glycans to different types of molecules,including proteins,lipids,and nucleic acids.Among these,protein glycosylation is one of the most prevalent forms of post-translational modification,playing a crucial role in biological complexity.With more than ten monosaccharides identified within mammalian brain cells and more than 1×1012 possible combinations,the heterogeneity of glycosylation is extensive(Conroy et al.,2021).The diversity of glycans and the complexity of their structures allow for a wide range of protein functions.N-glycans are one of the most abundant forms of glycans and are involved in various cellular functions.N-glycans can be added to proteins at specific sequons,Asn-X-Ser/Thr,and are classified into three main types in mature glycoproteins:high mannose,complex,and hybrid.High mannose N-glycans consist of 5-9 mannose residues linked to a chitobiose core and undergo processing into complex or hybrid forms in the Golgi apparatus(Varki et al.,2017).Complex N-glycans are more diverse and contain various branched structures such as antennae with fucose,galactose,and sialic acid residues.Hybrid N-glycans contain one or more complex branches in conjunction with an oligomannose branch(Fisher and Ungar,2016).Understanding the specific functions of these different types of N-glycans in protein regulation,folding,and function is an active area of research in the life sciences,including glycobiology.
基金supported by Defence Innovative Research Program(DIRP)Grant(PA No.9015102335)from Defence Research&Technology Office,Ministry of Defence,Singapore。
文摘Background:Excessive heat exposure can lead to hyperthermia in humans,which impairs physical performance and disrupts cognitive function.While heat is a known physiological stressor,it is unclear how severe heat stress affects brain physiology and function.Methods:Eleven healthy participants were subjected to heat stress from prolonged exercise or warm water immersion until their rectal temperatures(T_(re))attained 39.5℃,inducing exertional or passive hyperthermia,respectively.In a separate trial,blended ice was ingested before and during exercise as a cooling strategy.Data were compared to a control condition with seated rest(normothermic).Brain temperature(T_(br)),cerebral perfusion,and task-based brain activity were assessed using magnetic resonance imaging techniques.Results:T_(br)in motor cortex was found to be tightly regulated at rest(37.3℃±0.4℃(mean±SD))despite fluctuations in T_(re).With the development of hyperthermia,T_(br)increases and dovetails with the rising T_(re).Bilateral motor cortical activity was suppressed during high-intensity plantarflexion tasks,implying a reduced central motor drive in hyperthermic participants(T_(re)=38.5℃±0.1℃).Global gray matter perfusion and regional perfusion in sensorimotor cortex were reduced with passive hyperthermia.Executive function was poorer under a passive hyperthermic state,and this could relate to compromised visual processing as indicated by the reduced activation of left lateral-occipital cortex.Conversely,ingestion of blended ice before and during exercise alleviated the rise in both T_(re)and T_(bc)and mitigated heat-related neural perturbations.Conclusion:Severe heat exposure elevates T_(br),disrupts motor cortical activity and executive function,and this can lead to impairment of physical and cognitive performance.
基金supported by the U.S.National Institutes of Health(NIH)National Institute of Neurological Disorders and Stroke(NINDS),No.R01 NS134215(to UBP).
文摘The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding protein.As the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent protein.Although many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its discovery.In this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder itself.Additionally,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of study.This review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.
文摘Our brain is constantly active.Even at rest,the brain carries out essential functions such as maintenance of resting potentials,subthreshold synaptic activity,and spiking activity related to information processing.This resting activity can be assessed with several in vivo tools,such as resting-state functional magnetic resonance imaging.This technique measures subtle changes in blood flow,volume,and oxygenation that occur over time.Although vascular in nature,resting-state functional magnetic resonance imaging is considered a reliable proxy of neural activity and several studies have shown that the brain is functionally divided into interacting neural networks called the“functional connectome”.
文摘Functional magnetic resonance imaging(fMRI)is a popular tool used to investigate not only how the brain responds to specific stimuli during sensorimotor or cognitive tasks,but also brain activity at rest.The physics beyond this approach is based on the analysis of the blood oxygenation level-dependent signal.
基金supported by The David and Inez Myers Foundation,Beachwood,OH,USA(to DT)。
文摘With the increase of life expectancy and population growth,neurodegenerative diseases have risen too and are projected to be a major health public concern by 2050.Neurodegenerative diseases are characterized by the progressive decline of cognitive function leading to the subsequent loss of autonomy.Although the underlying causes of neurodegeneration are not well understood,aging is the main risk factor.
文摘The authors report a case of deficient sensory neuropathy secondary to vitamin B12 deficiency, diagnosed in the neurology department of the Sino-Central African Friendship University Hospital in Bangui. The diagnosis was made possible by electroneuromyography which showed subclinical neurological damage associated with hematological damage (anemia). Through this observation, we recall the diagnostic criteria of the disease in a context of difficult medical practice. .
基金funded by the National Science Foundation of China(Grant No.42161043)the improvement plan of scientific research ability in Northwest Normal University(NWNU-LKQN2020-16).
文摘The implementation of Ecological Function Protection Zone(EFPZ)policy is significant for the ecological restoration and conservation of soil and water in the territory space.This manuscript analyzed and quantified the impact of EFPZ on the regional water conservation function,based on land use data from 2005,2008,2010,2015 and 2020,by conducting a counterfactual simulation along with the GeoSOS-FLUS model and the InVEST model.The results demonstrate that the delineation of EFPZ can significantly influence the water conservation.(1)From 2010 to 2020,as the EFPZ was implemented,the water conservation in the study area was increasing year by year,with a growth rate of 0.03×10^(8) m^(3)∙a^(-1).On the other hand,the simulated water conservation capacity without the implementation of EFPZ decreased year by year,with a decrease rate of 0.01×10^(8) m^(3)∙a^(-1).(2)The EFPZ accounts for only 23%of the total area,but the contribution rate of water conservation reaches 80%.The actual values of water conservation and average water yield per unit pixel in the EFPZ show an increasing trend both internally and externally,while the counterfactual simulation values exhibit a decreasing trend.(3)The water conservation is much higher within the EFPZ than without EFPZ.The implementation of EFPZ has a significant effect on the improvement of the water conservation capacity in Maqu EFPZ and Yellow River Source EFPZ.The protection effectiveness should be enhanced in Qilian Mountain EFPZ and afforestation activities need to be carefully considered in Loess Plateau EFPZ.
