Globally,glaucoma stands as a primary cause of irreversible blindness,marked by intricate pathophysiological processes in which neuroinflammation plays a pivotal role.As the principal immune cells within the central n...Globally,glaucoma stands as a primary cause of irreversible blindness,marked by intricate pathophysiological processes in which neuroinflammation plays a pivotal role.As the principal immune cells within the central nervous system,microglia play a dual function in the progression of glaucoma.Under standard physiological states,microglia safeguard the retina by offering neurotrophic support and removing cellular debris.In the pathological progression of glaucoma,microglia become activated and release significant levels of inflammatory factors,resulting in retinal ganglion cell injury,cell death,and impaired neuroregeneration.This review focuses on examining the dual functions of microglia in glaucoma,evaluating their influence on retinal neurodegeneration and repair,and suggesting that modulating microglial activity could serve as a promising therapeutic strategy.Understanding the mechanisms of microglial action in glaucoma is crucial for unveiling the complex pathophysiological processes of the disease and developing new therapeutic strategies.展开更多
Acupuncture is potentially beneficial for post-stroke rehabilitation and is considered a promising preventive strategy for stroke.Electroacupuncture pretreatment or treatment after ischemic stroke by using appropriate...Acupuncture is potentially beneficial for post-stroke rehabilitation and is considered a promising preventive strategy for stroke.Electroacupuncture pretreatment or treatment after ischemic stroke by using appropriate electroacupuncture parameters generates neuroprotective and neuroregenerative effects that increase cerebral blood flow,regulate oxidative stress,attenuate glutamate excitotoxicity,maintain bloodbrain barrier integrity,inhibit apoptosis,increase growth factor production,and induce cerebral ischemic tolerance.展开更多
Neuronal networks,especially those in the central nervous system(CNS),evolved to support extensive functional capabilities while ensuring stability.Several physiological"brakes"that maintain the stability of...Neuronal networks,especially those in the central nervous system(CNS),evolved to support extensive functional capabilities while ensuring stability.Several physiological"brakes"that maintain the stability of the neuronal networks in a healthy state quickly become a hinderance postinjury.These"brakes"include inhibition from the extracellular environment,intrinsic factors of neurons and the control of neuronal plasticity.There are distinct differences between the neuronal networks in the peripheral nervous system(PNS)and the CNS.Underpinning these differences is the trade-off between reduced functional capabilities with increased adaptability through the formation of new connections and new neurons.The PNS has"facilitators"that stimulate neuroregeneration and plasticity,while the CNS has"brakes"that limit them.By studying how these"facilitators"and"brakes"work and identifying the key processes and molecules involved,we can attempt to apply these theories to the neuronal networks of the CNS to increase its adaptability.The difference in adaptability between the CNS and PNS leads to a difference in neuroregenerative properties and plasticity.Plasticity ensures quick functional recovery of abilities in the short and medium term.Neuroregeneration involves synthesizing new neurons and connections,providing extra resources in the long term to replace those damaged by the injury,and achieving a lasting functional recovery.Therefore,by understanding the factors that affect neuroregeneration and plasticity,we can combine their advantages and develop rehabilitation techniques.Rehabilitation training methods,coordinated with pharmacological interventions and/or electrical stimulation,contributes to a precise,holistic treatment plan that achieves functional recovery from nervous system injuries.Furthermore,these techniques are not limited to limb movement,as other functions lost as a result of brain injury,such as speech,can also be recovered with an appropriate training program.展开更多
Neurotrophins：Neurotrophins are peptides or proteins that are known to regulate neuronal viability,development,and function Beyond synaptic plasticity,neurotrophins protect neurons from apoptosis and also promote neu...Neurotrophins：Neurotrophins are peptides or proteins that are known to regulate neuronal viability,development,and function Beyond synaptic plasticity,neurotrophins protect neurons from apoptosis and also promote neurogenesis to recover neuronal defici even in adulthood.展开更多
Through complex mechanisms that guide axons to the appropriate routes towards their targets, axonal growth and guidance lead to neuronal system formation. These mechanisms establish the synaptic circuitry necessary fo...Through complex mechanisms that guide axons to the appropriate routes towards their targets, axonal growth and guidance lead to neuronal system formation. These mechanisms establish the synaptic circuitry necessary for the optimal performance of the nervous system in all organisms. Damage to these networks can be repaired by neuroregenerative processes which in turn can re-establish synapses between injured axons and postsynaptic terminals. Both axonal growth and guidance and the neuroregenerative response rely on correct axonal growth and growth cone responses to guidance cues as well as correct synapses with appropriate targets. With this in mind, parallels can be drawn between axonal regeneration and processes occurring during embryonic nervous system development. However, when studying parallels between axonal development and regeneration many questions still arise; mainly, how do axons grow and synapse with their targets and how do they repair their membranes, grow and orchestrate regenerative responses after injury. Major players in the cellular and molecular processes that lead to growth cone development and movement during embryonic development are the Soluble N-ethylamaleimide Sensitive Factor （NSF） Attachment Protein Receptor （SNARE） proteins, which have been shown to be involved in axonal growth and guidance. Their involvement in axonal growth, guidance and neuroregeneration is of foremost importance, due to their roles in vesicle and membrane trafficking events. Here, we review the recent literature on the involvement of SNARE proteins in axonal growth and guidance during embryonic development and neuroregeneration.展开更多
Purinergic signalling,adenosine 5′-triphosphate（ATP）as an extracellular signalling molecule,was proposed in 1972（Burnstock,1972）.However,it was not generally accepted until the early 1990s when receptors for ATP ...Purinergic signalling,adenosine 5′-triphosphate（ATP）as an extracellular signalling molecule,was proposed in 1972（Burnstock,1972）.However,it was not generally accepted until the early 1990s when receptors for ATP and its breakdown product adenosine were cloned and characterised（Ralevic and Burnstock,1998）.Four P1（adenosine）receptors are recognised（A1,A2A,A2B and A3）.展开更多
Cellular reprogramming is an innovative technology used to artificlally convert a mature cell type into a different cell type by molecular＇manipulation. The general concept of cellular reprogramming is to use master ...Cellular reprogramming is an innovative technology used to artificlally convert a mature cell type into a different cell type by molecular＇manipulation. The general concept of cellular reprogramming is to use master transcription factors to override the endogenous transcriptome profile of a given cell type with the transcriptome profile of the target cell type, thereby altering the cellular function and identity.展开更多
Neural Regeneration Research （NRR） is an international academic journal specialized in the field of neural regeneration research and published in English. The journal is supervised by the Ministry of Health, P.R. Ch...Neural Regeneration Research （NRR） is an international academic journal specialized in the field of neural regeneration research and published in English. The journal is supervised by the Ministry of Health, P.R. China, sponsored by the Chinese Association of Rehabilitation Medicine, and co-edited by the Editorial Department of Neural Regeneration Research and China Science Press.展开更多
Neural Regeneration Research （NRR） is an international academic journal specialized in the field of neural regeneration research and published in English. The journal is supervised by the Ministry of Health, P.R. Ch...Neural Regeneration Research （NRR） is an international academic journal specialized in the field of neural regeneration research and published in English. The journal is supervised by the Ministry of Health, P.R. China, sponsored by the Chinese Association of Rehabilitation Medicine, and co-edited by the Editorial Department of Neural Regeneration Research and China Science Press.展开更多
Totally three articles focusing on “the expression of Nogo-A, Nogo receptor and NADPH-diaphorase in the developing rat visual cortex and the effects of levodopa methyl ester on nerve growth factor expression in visua...Totally three articles focusing on “the expression of Nogo-A, Nogo receptor and NADPH-diaphorase in the developing rat visual cortex and the effects of levodopa methyl ester on nerve growth factor expression in visual cortex area 17 in strabismic amblyopia” are published in three issues. We hope that our readers find these papers useful to their research.展开更多
An experimental autolmmune encephalomyelitis model can be used to mimic pathological changes of multiple sclerosis from different angles. During the acute phase of experimental autolmmune encephalomyelitis, CD4＋ T-ce...An experimental autolmmune encephalomyelitis model can be used to mimic pathological changes of multiple sclerosis from different angles. During the acute phase of experimental autolmmune encephalomyelitis, CD4＋ T-cells in the central nervous system infiltrate, proliferate, release large amounts of pro-inflammatory cytokines, and activate the inflammatory cascade, which ultimately leads to展开更多
Hypoxia is a condition found commonly in several disorders,such as ischemia,asthma,anemia and neonatal hypoxia.Individuals subjected suddenly to high altitude or extreme exercise are also challenged to low oxygen（O2...Hypoxia is a condition found commonly in several disorders,such as ischemia,asthma,anemia and neonatal hypoxia.Individuals subjected suddenly to high altitude or extreme exercise are also challenged to low oxygen（O2）levels.Since the brain presents elevated basal O_2 consumption,this organ is readily affected by hypoxia.For this reason,展开更多
Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within t...Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within the ischemic brain,these mechanisms are often insufficient to restore neuronal functionality.This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option.This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events,with focus on the impact of stem cell-based therapies on neural stem cells.Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-tocell contact and through the secretion of growth factors and exosomes.Additionally,implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called“biobridges.”Furthermore,xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects,thereby supporting endogenous neuroregeneration.Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment,we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types.These approaches include:(1)co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis;(2)synergistic administration of stem cells and their exosomes to amplify paracrine effects;and(3)integration of stem cells within hydrogels,which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits.This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.展开更多
The ErbB signaling network has recently emerged as a key modulator of central nervous system responses to injury.This review provides a comprehensive overview of ErbB receptors and their ligands,highlighting canonical...The ErbB signaling network has recently emerged as a key modulator of central nervous system responses to injury.This review provides a comprehensive overview of ErbB receptors and their ligands,highlighting canonical and non-canonical signaling mechanisms relevant to brain damage.We explore how ErbB signaling is dynamically regulated following injury and how it orchestrates processes such as neuroinflammation,gliosis,and neural repair.Special attention is given to its interplay with other critical pathways,including Notch signaling,and its roles within adult neurogenic niches,where it modulates neural stem cell behavior in response to damage.Based on accumulating preclinical evidence,we propose two therapeutic strategies for targeting ErbB signaling in brain injury:(1)dampening neuroinflammation through ErbB inhibition and(2)promoting neuroprotection and neurogenesis via neuregulin-1-mediated activation.The first strategy is supported by studies,which demonstrate that inhibition of ErbB1 limits neuroinflammation and supports neural repair in preclinical models.The latter strategy is supported by emerging studies demonstrating the significant potential of novel protein kinase C activating diterpenes in modulating ErbB signaling pathways through the regulation of neuregulin-1 release.Diterpenes,by influencing the ErbB pathway,may uniquely bridge the gap between neuroprotection and regeneration.Their potential to modulate inflammation and promote pro-regenerative cellular environments positions them as promising tools in the development of targeted therapies.By dissecting these mechanisms,we aim to shed light on the translational potential of ErbB-targeted therapies and their capacity to enhance endogenous repair processes in the injured brain.展开更多
Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to p...Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.展开更多
The heart and brain are functionally synchronized through the heart-brain axis,also known as the neurocardiac axis.Astrocytes are the predominant subpopulation of glial cells in the central nervous system that play an...The heart and brain are functionally synchronized through the heart-brain axis,also known as the neurocardiac axis.Astrocytes are the predominant subpopulation of glial cells in the central nervous system that play an integral role in maintaining homeostasis,neurovascular coupling,and synaptic transmission.Radial astroglia are recognized as a potential source for the generation of new neurons in the brain,a process known as neurogenesis,accounting for neuroplasticity.While brain-resident astrocytes have been extensively studied,increasing experimental evidence has demonstrated the presence of astroglial-like cells in various organs,including the heart.The existence of astrocyte-like cells in the heart,known as cardiac nexus glia,is recognized as an emerging key modulator of cardiac function and blood flow.Similar to astrocytes,cardiac nexus glia can also release different gliotransmitters,including brain-derived neurotrophic factor,thereby modulating neurocardiac interactions.This review delves into the mechanistic insights of the cardiac nexus glia and emphasizes a hypothesis that these glial cells may possess the multipotent capacity to generate neurons,astrocytes,and oligodendrocytes,suggesting that peripheral neurogenesis could occur in the heart.As astrocytes are vital for neuroplasticity,the regulation of cardiac nexus glia may support heart–brain communication,while their dysfunction could lead to neurocardiac disorders.展开更多
This article focused on the recent contribution by Jiang et al,who demonstrated that voluntary exercise can significantly potentiate the effects of induced pluripotent stem cell transplantation in a Parkinson’s disea...This article focused on the recent contribution by Jiang et al,who demonstrated that voluntary exercise can significantly potentiate the effects of induced pluripotent stem cell transplantation in a Parkinson’s disease(PD)model through activation of the Wnt1-Lmx1a signaling cascade.Jiang et al’s findings highlight the role of exercise as a molecular modulator of neurogenesis and support the development of integrated strategies combining physical activity,stem cell transplantation,and biomaterials to improve outcomes in PD.We highlight exercise as a molecular modulator that fosters a neurogenic milieu,recommend examining additional developmental signals(sonic hedgehog,fibroblast growth factor 8,bone morphogenetic protein),and suggest biomaterial-based strategies to support graft survival and integration.We also stress the need to optimize exercise regimens in relation to transplantation,framing these insights within a translational strategy for advancing regenerative therapies in PD.展开更多
BACKGROUND Traumatic brain injury(TBI)is a significant public health issue,leading to long-term neurological impairments.Current treatments offer limited recovery,particularly in restoring lost functions.Mesenchymal s...BACKGROUND Traumatic brain injury(TBI)is a significant public health issue,leading to long-term neurological impairments.Current treatments offer limited recovery,particularly in restoring lost functions.Mesenchymal stem cell-derived exosomes(MSCdE)have shown potential for promoting neuroprotection and regeneration.This study evaluates the safety and efficacy of MSCdE therapy in TBI patients.AIM To evaluate the safety and efficacy of MSCdE therapy in TBI patients.METHODS Five patients(mean age 27.00±4.06 years)with TBI from combat injuries were treated with six rounds of MSCdE therapy(3 mL intrathecally and 3 mL intramuscularly per round).The patients were followed for one year.Adverse events were assessed using the Common Terminology Criteria for Adverse Events version 5.0(CTCAE v5.0),and functional outcomes were evaluated with the functional independence measure(FIM),Modified Ashworth Scale(MAS),and Karnofsky Performance Scale(KPS).RESULTS No serious adverse events occurred,and only mild side effects[subfebrile fever(37.5°C-37.9°C),pain]were reported(CTCAE Grade 1).FIM motor scores improved significantly(46.20±16.39 to 64.20±18.20,P<0.01),and FIM cognitive scores also showed significant improvement(30.60±4.56 to 34.00±1.41,P<0.001).While MAS scores improved(right/left:4.60/3.60 to 2.20/1.60),these changes were not statistically significant(P>0.05),possibly due to low baseline spasticity.KPS scores significantly improved(46.00±11.40 to 72.00±8.37,P<0.001),indicating enhanced overall functional status and quality of life.CONCLUSION MSCdE therapy is safe and effective in improving motor function,cognition,and quality of life in TBI patients.Larger,controlled trials are needed to further validate these findings and optimize MSCdE therapy for TBI treatment.展开更多
Previous studies have demonstrated the protective effect of hypoxic preconditioning on acute cerebral infarction, but the mechanisms underlying this protection remain unclear. To investigate the protective mechanisms ...Previous studies have demonstrated the protective effect of hypoxic preconditioning on acute cerebral infarction, but the mechanisms underlying this protection remain unclear. To investigate the protective mechanisms of hypoxic preconditioning in relation to its effects on angiogenesis, we in- duced a photochemical model of cerebral infarction in an inbred line of mice （BALB/c）. Mice were then exposed to hypoxic preconditioning 30 minutes prior to model establishment. Results showed significantly increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra at 24 and 72 hours post infarction, mainly in neurons and vascular endothelial cells. Hypoxic preconditioning increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra and the expression of vascular endothelial growth factor was positively related to that of CD31. Moreover, hypoxic preconditioning reduced the infarct volume and improved neu- rological function in mice. These findings indicate that the protective role of hypoxic preconditioning in acute cerebral infarction may possibly be due to an increase in expression of vascular endothelial growth factor and CD31 in the ischemic penumbra, which promoted angiogenesis.展开更多
A total of 64 patients with acute lacunar infarction were enrolled within 24 hours of onset. The patients received conventional therapy （antiplatelet drugs and hypolipidemic drugs） alone or conventional therapy plus...A total of 64 patients with acute lacunar infarction were enrolled within 24 hours of onset. The patients received conventional therapy （antiplatelet drugs and hypolipidemic drugs） alone or conventional therapy plus 450 mg Xueshuantong once a day. The main ingredient of the Xueshuantong lyophilized powder used for injection was Panax notoginseng saponins. Assessments were made at admission and at discharge using the National Institutes of Health Stroke Scale, the Activity of Daily Living and the Mini-Mental State Examination. Additionally, the relative cerebral blood flow, relative cerebral blood volume and relative mean transit time in the region of interest were calculated within 24 hours after the onset of lacunar infarction, using dynamic susceptibility contrast magnetic resonance perfusion imaging technology. Patients underwent a follow-up MRI scan after 4 weeks of treatment. There was an improvement in the Activity of Daily Living scores and a greater reduction in the scores on the National Institutes of Health Stroke Scale in the treatment group than in the control group. However, the Mini-Mental State Examination scores showed no significant differences after 4 weeks of treatment. Compared with the control group, the relative cerebral blood flow at discharge had increased and showed a greater improvement in the treatment group. Furthermore, there was a reduction in the relative mean transit time at discharge and the value was lower in the treatment group than in the control group. The experimental findings indicate that Xueshuantong treatment improves neurological deficits in elderly patients with lacunar infarction, and the mechanism may be related to increased cerebral perfusion.展开更多
基金supported by the Deutsche Forschungsgemeinschaft(DFG)with grants PR1569/1-1 and PR 1569/1-3(to VP).
文摘Globally,glaucoma stands as a primary cause of irreversible blindness,marked by intricate pathophysiological processes in which neuroinflammation plays a pivotal role.As the principal immune cells within the central nervous system,microglia play a dual function in the progression of glaucoma.Under standard physiological states,microglia safeguard the retina by offering neurotrophic support and removing cellular debris.In the pathological progression of glaucoma,microglia become activated and release significant levels of inflammatory factors,resulting in retinal ganglion cell injury,cell death,and impaired neuroregeneration.This review focuses on examining the dual functions of microglia in glaucoma,evaluating their influence on retinal neurodegeneration and repair,and suggesting that modulating microglial activity could serve as a promising therapeutic strategy.Understanding the mechanisms of microglial action in glaucoma is crucial for unveiling the complex pathophysiological processes of the disease and developing new therapeutic strategies.
基金supported under the Aim for the Top University Plan of the Ministry of Education,Taiwan,China
文摘Acupuncture is potentially beneficial for post-stroke rehabilitation and is considered a promising preventive strategy for stroke.Electroacupuncture pretreatment or treatment after ischemic stroke by using appropriate electroacupuncture parameters generates neuroprotective and neuroregenerative effects that increase cerebral blood flow,regulate oxidative stress,attenuate glutamate excitotoxicity,maintain bloodbrain barrier integrity,inhibit apoptosis,increase growth factor production,and induce cerebral ischemic tolerance.
文摘Neuronal networks,especially those in the central nervous system(CNS),evolved to support extensive functional capabilities while ensuring stability.Several physiological"brakes"that maintain the stability of the neuronal networks in a healthy state quickly become a hinderance postinjury.These"brakes"include inhibition from the extracellular environment,intrinsic factors of neurons and the control of neuronal plasticity.There are distinct differences between the neuronal networks in the peripheral nervous system(PNS)and the CNS.Underpinning these differences is the trade-off between reduced functional capabilities with increased adaptability through the formation of new connections and new neurons.The PNS has"facilitators"that stimulate neuroregeneration and plasticity,while the CNS has"brakes"that limit them.By studying how these"facilitators"and"brakes"work and identifying the key processes and molecules involved,we can attempt to apply these theories to the neuronal networks of the CNS to increase its adaptability.The difference in adaptability between the CNS and PNS leads to a difference in neuroregenerative properties and plasticity.Plasticity ensures quick functional recovery of abilities in the short and medium term.Neuroregeneration involves synthesizing new neurons and connections,providing extra resources in the long term to replace those damaged by the injury,and achieving a lasting functional recovery.Therefore,by understanding the factors that affect neuroregeneration and plasticity,we can combine their advantages and develop rehabilitation techniques.Rehabilitation training methods,coordinated with pharmacological interventions and/or electrical stimulation,contributes to a precise,holistic treatment plan that achieves functional recovery from nervous system injuries.Furthermore,these techniques are not limited to limb movement,as other functions lost as a result of brain injury,such as speech,can also be recovered with an appropriate training program.
文摘Neurotrophins：Neurotrophins are peptides or proteins that are known to regulate neuronal viability,development,and function Beyond synaptic plasticity,neurotrophins protect neurons from apoptosis and also promote neurogenesis to recover neuronal defici even in adulthood.
基金supported by the Ramon y Cajal programme(RYC-2007-00417,RYC-2009-05510)grants from the Spanish MINECO(SAF2013-42445R and BFU2010-21507)CIBERNED
文摘Through complex mechanisms that guide axons to the appropriate routes towards their targets, axonal growth and guidance lead to neuronal system formation. These mechanisms establish the synaptic circuitry necessary for the optimal performance of the nervous system in all organisms. Damage to these networks can be repaired by neuroregenerative processes which in turn can re-establish synapses between injured axons and postsynaptic terminals. Both axonal growth and guidance and the neuroregenerative response rely on correct axonal growth and growth cone responses to guidance cues as well as correct synapses with appropriate targets. With this in mind, parallels can be drawn between axonal regeneration and processes occurring during embryonic nervous system development. However, when studying parallels between axonal development and regeneration many questions still arise; mainly, how do axons grow and synapse with their targets and how do they repair their membranes, grow and orchestrate regenerative responses after injury. Major players in the cellular and molecular processes that lead to growth cone development and movement during embryonic development are the Soluble N-ethylamaleimide Sensitive Factor （NSF） Attachment Protein Receptor （SNARE） proteins, which have been shown to be involved in axonal growth and guidance. Their involvement in axonal growth, guidance and neuroregeneration is of foremost importance, due to their roles in vesicle and membrane trafficking events. Here, we review the recent literature on the involvement of SNARE proteins in axonal growth and guidance during embryonic development and neuroregeneration.
文摘Purinergic signalling,adenosine 5′-triphosphate（ATP）as an extracellular signalling molecule,was proposed in 1972（Burnstock,1972）.However,it was not generally accepted until the early 1990s when receptors for ATP and its breakdown product adenosine were cloned and characterised（Ralevic and Burnstock,1998）.Four P1（adenosine）receptors are recognised（A1,A2A,A2B and A3）.
基金supported by grants from the National Health and Medical Research Council(1084256)the University of Melbourne(Louisa Jean De Bretteville Bequest)as well as the Medical Advances Without Animals Trust FellowshipThe Centre for Eye Research Australia receives operational infrastructure support from the Victorian Government
文摘Cellular reprogramming is an innovative technology used to artificlally convert a mature cell type into a different cell type by molecular＇manipulation. The general concept of cellular reprogramming is to use master transcription factors to override the endogenous transcriptome profile of a given cell type with the transcriptome profile of the target cell type, thereby altering the cellular function and identity.
文摘Neural Regeneration Research （NRR） is an international academic journal specialized in the field of neural regeneration research and published in English. The journal is supervised by the Ministry of Health, P.R. China, sponsored by the Chinese Association of Rehabilitation Medicine, and co-edited by the Editorial Department of Neural Regeneration Research and China Science Press.
文摘Neural Regeneration Research （NRR） is an international academic journal specialized in the field of neural regeneration research and published in English. The journal is supervised by the Ministry of Health, P.R. China, sponsored by the Chinese Association of Rehabilitation Medicine, and co-edited by the Editorial Department of Neural Regeneration Research and China Science Press.
文摘Totally three articles focusing on “the expression of Nogo-A, Nogo receptor and NADPH-diaphorase in the developing rat visual cortex and the effects of levodopa methyl ester on nerve growth factor expression in visual cortex area 17 in strabismic amblyopia” are published in three issues. We hope that our readers find these papers useful to their research.
文摘An experimental autolmmune encephalomyelitis model can be used to mimic pathological changes of multiple sclerosis from different angles. During the acute phase of experimental autolmmune encephalomyelitis, CD4＋ T-cells in the central nervous system infiltrate, proliferate, release large amounts of pro-inflammatory cytokines, and activate the inflammatory cascade, which ultimately leads to
基金Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)INCT-Excitoxicidade e Neuroprotecao and by FINEP research grant “Rede Instituto Brasileiro de Neurociencia (IBN-Net)” #01.06.0842-00
文摘Hypoxia is a condition found commonly in several disorders,such as ischemia,asthma,anemia and neonatal hypoxia.Individuals subjected suddenly to high altitude or extreme exercise are also challenged to low oxygen（O2）levels.Since the brain presents elevated basal O_2 consumption,this organ is readily affected by hypoxia.For this reason,
基金supported by the National Key Research and Development Program of China,No.2018YFA0108602the CAMS Initiative for Innovative Medicine,No.2021-1-I2M-019National High-Level Hospital Clinical Research Funding,No.2022-PUMCH-C-042(all to XB)。
文摘Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within the ischemic brain,these mechanisms are often insufficient to restore neuronal functionality.This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option.This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events,with focus on the impact of stem cell-based therapies on neural stem cells.Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-tocell contact and through the secretion of growth factors and exosomes.Additionally,implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called“biobridges.”Furthermore,xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects,thereby supporting endogenous neuroregeneration.Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment,we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types.These approaches include:(1)co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis;(2)synergistic administration of stem cells and their exosomes to amplify paracrine effects;and(3)integration of stem cells within hydrogels,which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits.This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.
基金supported by the I+D+i(PID2022-142418OB-C21)grant funded by MICIU/AEI/10.13039/501100011033 and by ERDF/UE.
文摘The ErbB signaling network has recently emerged as a key modulator of central nervous system responses to injury.This review provides a comprehensive overview of ErbB receptors and their ligands,highlighting canonical and non-canonical signaling mechanisms relevant to brain damage.We explore how ErbB signaling is dynamically regulated following injury and how it orchestrates processes such as neuroinflammation,gliosis,and neural repair.Special attention is given to its interplay with other critical pathways,including Notch signaling,and its roles within adult neurogenic niches,where it modulates neural stem cell behavior in response to damage.Based on accumulating preclinical evidence,we propose two therapeutic strategies for targeting ErbB signaling in brain injury:(1)dampening neuroinflammation through ErbB inhibition and(2)promoting neuroprotection and neurogenesis via neuregulin-1-mediated activation.The first strategy is supported by studies,which demonstrate that inhibition of ErbB1 limits neuroinflammation and supports neural repair in preclinical models.The latter strategy is supported by emerging studies demonstrating the significant potential of novel protein kinase C activating diterpenes in modulating ErbB signaling pathways through the regulation of neuregulin-1 release.Diterpenes,by influencing the ErbB pathway,may uniquely bridge the gap between neuroprotection and regeneration.Their potential to modulate inflammation and promote pro-regenerative cellular environments positions them as promising tools in the development of targeted therapies.By dissecting these mechanisms,we aim to shed light on the translational potential of ErbB-targeted therapies and their capacity to enhance endogenous repair processes in the injured brain.
基金supported by the Natio`nal Natural Science Foundation of China,No. 81801241a grant from Sichuan Science and Technology Program,No. 2023NSFSC1578Scientific Research Projects of Southwest Medical University,No. 2022ZD002 (all to JX)。
文摘Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.
基金Supported by UGC-FRPRashtriya Uchchatar Shiksha Abhiyan(RUSA)2.0,Biological Sciences,Bharathidasan University,No.TN RUSA:311/RUSA(2.0)/2018+1 种基金Anusandhan National Research Foundation(ANRF)/Science Engineering Research Board(SERB),No.CRG/2023/005266and UGC-SAP and DST-FIST to the Department of Animal Science,Bharathidasan University.
文摘The heart and brain are functionally synchronized through the heart-brain axis,also known as the neurocardiac axis.Astrocytes are the predominant subpopulation of glial cells in the central nervous system that play an integral role in maintaining homeostasis,neurovascular coupling,and synaptic transmission.Radial astroglia are recognized as a potential source for the generation of new neurons in the brain,a process known as neurogenesis,accounting for neuroplasticity.While brain-resident astrocytes have been extensively studied,increasing experimental evidence has demonstrated the presence of astroglial-like cells in various organs,including the heart.The existence of astrocyte-like cells in the heart,known as cardiac nexus glia,is recognized as an emerging key modulator of cardiac function and blood flow.Similar to astrocytes,cardiac nexus glia can also release different gliotransmitters,including brain-derived neurotrophic factor,thereby modulating neurocardiac interactions.This review delves into the mechanistic insights of the cardiac nexus glia and emphasizes a hypothesis that these glial cells may possess the multipotent capacity to generate neurons,astrocytes,and oligodendrocytes,suggesting that peripheral neurogenesis could occur in the heart.As astrocytes are vital for neuroplasticity,the regulation of cardiac nexus glia may support heart–brain communication,while their dysfunction could lead to neurocardiac disorders.
文摘This article focused on the recent contribution by Jiang et al,who demonstrated that voluntary exercise can significantly potentiate the effects of induced pluripotent stem cell transplantation in a Parkinson’s disease(PD)model through activation of the Wnt1-Lmx1a signaling cascade.Jiang et al’s findings highlight the role of exercise as a molecular modulator of neurogenesis and support the development of integrated strategies combining physical activity,stem cell transplantation,and biomaterials to improve outcomes in PD.We highlight exercise as a molecular modulator that fosters a neurogenic milieu,recommend examining additional developmental signals(sonic hedgehog,fibroblast growth factor 8,bone morphogenetic protein),and suggest biomaterial-based strategies to support graft survival and integration.We also stress the need to optimize exercise regimens in relation to transplantation,framing these insights within a translational strategy for advancing regenerative therapies in PD.
文摘BACKGROUND Traumatic brain injury(TBI)is a significant public health issue,leading to long-term neurological impairments.Current treatments offer limited recovery,particularly in restoring lost functions.Mesenchymal stem cell-derived exosomes(MSCdE)have shown potential for promoting neuroprotection and regeneration.This study evaluates the safety and efficacy of MSCdE therapy in TBI patients.AIM To evaluate the safety and efficacy of MSCdE therapy in TBI patients.METHODS Five patients(mean age 27.00±4.06 years)with TBI from combat injuries were treated with six rounds of MSCdE therapy(3 mL intrathecally and 3 mL intramuscularly per round).The patients were followed for one year.Adverse events were assessed using the Common Terminology Criteria for Adverse Events version 5.0(CTCAE v5.0),and functional outcomes were evaluated with the functional independence measure(FIM),Modified Ashworth Scale(MAS),and Karnofsky Performance Scale(KPS).RESULTS No serious adverse events occurred,and only mild side effects[subfebrile fever(37.5°C-37.9°C),pain]were reported(CTCAE Grade 1).FIM motor scores improved significantly(46.20±16.39 to 64.20±18.20,P<0.01),and FIM cognitive scores also showed significant improvement(30.60±4.56 to 34.00±1.41,P<0.001).While MAS scores improved(right/left:4.60/3.60 to 2.20/1.60),these changes were not statistically significant(P>0.05),possibly due to low baseline spasticity.KPS scores significantly improved(46.00±11.40 to 72.00±8.37,P<0.001),indicating enhanced overall functional status and quality of life.CONCLUSION MSCdE therapy is safe and effective in improving motor function,cognition,and quality of life in TBI patients.Larger,controlled trials are needed to further validate these findings and optimize MSCdE therapy for TBI treatment.
基金supported by the National Natural Science Foundation of China,No.30870854the Natural Science Foundation of Beijing,No.7111003the Natural Science Foundation of Shandong Province,No.ZR2010HM029
文摘Previous studies have demonstrated the protective effect of hypoxic preconditioning on acute cerebral infarction, but the mechanisms underlying this protection remain unclear. To investigate the protective mechanisms of hypoxic preconditioning in relation to its effects on angiogenesis, we in- duced a photochemical model of cerebral infarction in an inbred line of mice （BALB/c）. Mice were then exposed to hypoxic preconditioning 30 minutes prior to model establishment. Results showed significantly increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra at 24 and 72 hours post infarction, mainly in neurons and vascular endothelial cells. Hypoxic preconditioning increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra and the expression of vascular endothelial growth factor was positively related to that of CD31. Moreover, hypoxic preconditioning reduced the infarct volume and improved neu- rological function in mice. These findings indicate that the protective role of hypoxic preconditioning in acute cerebral infarction may possibly be due to an increase in expression of vascular endothelial growth factor and CD31 in the ischemic penumbra, which promoted angiogenesis.
基金supported by the Technological Foundation Project of Traditional Chinese Medicine Science of Zhejiang Province,No.2012ZA077
文摘A total of 64 patients with acute lacunar infarction were enrolled within 24 hours of onset. The patients received conventional therapy （antiplatelet drugs and hypolipidemic drugs） alone or conventional therapy plus 450 mg Xueshuantong once a day. The main ingredient of the Xueshuantong lyophilized powder used for injection was Panax notoginseng saponins. Assessments were made at admission and at discharge using the National Institutes of Health Stroke Scale, the Activity of Daily Living and the Mini-Mental State Examination. Additionally, the relative cerebral blood flow, relative cerebral blood volume and relative mean transit time in the region of interest were calculated within 24 hours after the onset of lacunar infarction, using dynamic susceptibility contrast magnetic resonance perfusion imaging technology. Patients underwent a follow-up MRI scan after 4 weeks of treatment. There was an improvement in the Activity of Daily Living scores and a greater reduction in the scores on the National Institutes of Health Stroke Scale in the treatment group than in the control group. However, the Mini-Mental State Examination scores showed no significant differences after 4 weeks of treatment. Compared with the control group, the relative cerebral blood flow at discharge had increased and showed a greater improvement in the treatment group. Furthermore, there was a reduction in the relative mean transit time at discharge and the value was lower in the treatment group than in the control group. The experimental findings indicate that Xueshuantong treatment improves neurological deficits in elderly patients with lacunar infarction, and the mechanism may be related to increased cerebral perfusion.
