Human spinal cord organoids(hSCOs)offer a promising platform to study neurotrauma by addressing many limitations of traditional research models.These organoids provide access to human-specific physiological and geneti...Human spinal cord organoids(hSCOs)offer a promising platform to study neurotrauma by addressing many limitations of traditional research models.These organoids provide access to human-specific physiological and genetic mechanisms and can be derived from an individual's somatic cells(e.g.,blood or skin).This enables patient-specific paradigms for precision neurotrauma research,pa rticula rly relevant to the over 300,000 people in the United States living with chronic effects of spinal cord injury(SCI).展开更多
Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychoso...Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.展开更多
Spinal cord injury(SCI)refers to the impairment of neural structure and its function in spinal canal caused by various reasons,resulting in spinal cord dysfunction below the injury level.Currently,the most commonly us...Spinal cord injury(SCI)refers to the impairment of neural structure and its function in spinal canal caused by various reasons,resulting in spinal cord dysfunction below the injury level.Currently,the most commonly used sensory assessment scale for individuals with SCI is the American Spinal Cord Injury Association(ASIA)score,which can quickly identify the spinal level of sensory deficit.However,the ASIA can only identify the sensory impairment in SCI as 3-level,which is not accurate expression of sensory deficit in patients with SCI.展开更多
Spinal cord injury(SCI)interrupts the flow of information between the brain and the spinal cord,thus leading to a loss of sensory information and motor paralysis of the body below the lesion.Surprisingly,most SCIs are...Spinal cord injury(SCI)interrupts the flow of information between the brain and the spinal cord,thus leading to a loss of sensory information and motor paralysis of the body below the lesion.Surprisingly,most SCIs are incomplete and spare supraspinal pathways,especially those located within the peripheral white matter of the spinal cord,which includes reticulospinal pathways originating from the medullary reticular formation.Whereas there is abundant literature about the motor cortex,its corticospinal pathway,and its capacity to modulate functional recovery after SCI,less is known about the medullary reticular formation and its reticulospinal pathway.展开更多
Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these...Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface electromyography.In this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury.Eleven patients with chronic complete thoracic spinal cord injury were recruited.Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol.The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation.Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically significant.These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.展开更多
Spinal cord injury(SCI) often results in permanent dysfunction of locomotion,sensation,and autonomic regulation,imposing a substantial burden on both individuals and society(Anjum et al.,2020).SCI has a complex pathop...Spinal cord injury(SCI) often results in permanent dysfunction of locomotion,sensation,and autonomic regulation,imposing a substantial burden on both individuals and society(Anjum et al.,2020).SCI has a complex pathophysiology:an initial primary injury(mechanical trauma,axonal disruption,and hemorrhage) is followed by a progressive secondary injury cascade that involves ischemia,neuronal loss,and inflammation.Given the challenges in achieving regeneration of the injured spinal cord,neuroprotection has been at the forefront of clinical research.展开更多
Spinal cord injury(SCI)is a debilitating ailment that leads to the loss of motor and sensory functions,often leaving the patient paralyzed below the injury site(Chen et al.,2013).Globally around 250,000-300,000 people...Spinal cord injury(SCI)is a debilitating ailment that leads to the loss of motor and sensory functions,often leaving the patient paralyzed below the injury site(Chen et al.,2013).Globally around 250,000-300,000 people are diagnosed with SCI annually(Singh et al.,2014),and while this number appears quite low,the effect that an SCI has on the patient’s quality of life is drastic,due to the current difficulties to comprehensively treat this illness.The cost of patient care can also be quite costly,amounting to an estimated$1.69 billion in healthcare costs in the USA alone(Mahabaleshwarkar and Khanna,2014).展开更多
Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are ne...Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.展开更多
Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery ...Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.展开更多
Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challengin...Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury–specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research(in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc(AXER-204), fasudil, phosphatase and tensin homolog protein antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide,(-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidates have been identified through basic research, and these candidates may be subjects of clinical studies in the future. Moreover, cocktail therapy comprising drugs with varied underlying mechanisms may be effective in treating the refractory status of chronic spinal cord injury.展开更多
Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they cause.Despite the ongoing development of various therapies for spinal cord injuries,their effectiveness ...Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they cause.Despite the ongoing development of various therapies for spinal cord injuries,their effectiveness remains unsatisfactory.However,a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming.In this review,we explore the metabolic changes that occur during spinal cord injuries,their consequences,and the therapeutic tools available for metabolic reprogramming.Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling.However,spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism,lipid metabolism,and mitochondrial dysfunction.These metabolic disturbances lead to corresponding pathological changes,including the failure of axonal regeneration,the accumulation of scarring,and the activation of microglia.To rescue spinal cord injury at the metabolic level,potential metabolic reprogramming approaches have emerged,including replenishing metabolic substrates,reconstituting metabolic couplings,and targeting mitochondrial therapies to alter cell fate.The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury.To further advance the metabolic treatment of the spinal cord injury,future efforts should focus on a deeper understanding of neurometabolism,the development of more advanced metabolomics technologies,and the design of highly effective metabolic interventions.展开更多
Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a s...Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.展开更多
Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration...Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.展开更多
The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia ...The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.展开更多
Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accou...Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal regeneration.In this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor cells.Despite a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive research.This review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.展开更多
Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand...Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after injury.Recent studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for treatment.This review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord injury.Additionally,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted drugs.Nevertheless,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.展开更多
One serious lesion to the central nervous system is spinal cord injury (SCI). Due to its intricate pathophysiological mechanisms and the irreparability of nerve cells, conventional rehabilitation approaches often prov...One serious lesion to the central nervous system is spinal cord injury (SCI). Due to its intricate pathophysiological mechanisms and the irreparability of nerve cells, conventional rehabilitation approaches often prove inadequate for achieving full recovery. Consequently, most patients can only enhance their capacity for self-care in daily activities through early and proactive rehabilitation interventions. Stem cells are a class of cells that have the capacity to differentiate and are capable of safely and effectively differentiating into various types of neurons to repair or compensate for damaged cells, thereby exerting therapeutic effects. Currently, research on stem cell-based therapeutics for SCI is actively progressing and has yielded promising results. We discussed the anatomy, pathophysiological, the potential mechanisms of traditional therapy and stem cell therapy for SCI. The types of stem cells commonly used in current research and the latest progress in spinal cord therapy are described. Hope to serve as a resource for the use of stem cells in clinical settings.展开更多
Background:Although decompression surgery is the optimal treatment for patients with severe degenerative cervical myelopathy(DCM),some individuals experience no improvement or even a decline in neurological function a...Background:Although decompression surgery is the optimal treatment for patients with severe degenerative cervical myelopathy(DCM),some individuals experience no improvement or even a decline in neurological function after surgery,with spinal cord ischemia–reperfusion injury(SCII)identified as the primary cause.Spinal cord compression results in local ischemia and blood perfusion following decompression is fundamental to SCII.However,owing to inadequate perioperative blood flow monitoring,direct evidence regarding the occurrence of SCII after decompression is lacking.The objective of this study was to establish a suitable animal model for investigating the underlying mechanism of spinal cord ischemia–reperfusion injury following decom-pression surgery for degenerative cervical myelopathy(DCM)and to elucidate alterations in neurological function and local blood flow within the spinal cord before and after decompression.Methods:Twenty-four Sprague–Dawley rats were allocated to three groups:the DCM group(cervical compression group,with implanted compression material in the spinal canal,n=8),the DCM-D group(cervical decompression group,with removal of compression material from the spinal canal 4 weeks after implantation,n=8),and the SHAM group(sham operation,n=8).Von Frey test,forepaw grip strength,and gait were assessed within 4 weeks post-implantation.Spinal cord compression was evaluated using magnetic resonance imaging.Local blood flow in the spinal cord was monitored during the perioperative decompression.The rats were sacrificed 1 week after decompression to observe morphological changes in the compressed or decompressed segments of the spinal cord.Additionally,NeuN expression and the oxidative damage marker 8-oxoG DNA were analyzed.Results:Following spinal cord compression,abnormal mechanical pain worsened,and a decrease in forepaw grip strength was observed within 1–4 weeks.Upon decompression,the abnormal mechanical pain subsided,and forepaw grip strength was restored;however,neither reached the level of the sham operation group.Decompression leads to an increase in the local blood flow,indicating improved perfusion of the spinal cord.The number of NeuN-positive cells in the spinal cord of rats in the DCM-D group exceeded that in the DCM group but remained lower than that in the SHAM group.Notably,a higher level of 8-oxoG DNA expression was observed,suggesting oxidative stress following spinal cord decompression.Conclusion:This model is deemed suitable for analyzing the underlying mechanism of SCII following decompressive cervical laminectomy,as we posit that the obtained results are comparable to the clinical progression of degenerative cervical myelopathy(DCM)post-decompression and exhibit analogous neurological alterations.Notably,this model revealed ischemic reperfusion in the spinal cord after decompression,concomitant with oxidative damage,which plausibly underlies the neurological deterioration observed after decompression.展开更多
Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery...Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this population.Following the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing research.In this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the pathology.We study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular patterns.Several effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord injury.Following this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human subjects.This review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.展开更多
Every day walking consists of frequent voluntary modifications in the gait pattern to negotiate obstacles.After spinal cord injury,stepping over an obstacle becomes challenging.Stepping over an obstacle requires senso...Every day walking consists of frequent voluntary modifications in the gait pattern to negotiate obstacles.After spinal cord injury,stepping over an obstacle becomes challenging.Stepping over an obstacle requires sensorimotor transformations in several structures of the brain,including the parietal cortex,premotor cortex,and motor cortex.Sensory information and planning are transformed into motor commands,which are sent from the motor cortex to spinal neuronal circuits to alter limb trajectory,coordinate the limbs,and maintain balance.After spinal cord injury,bidirectional communication between the brain and spinal cord is disrupted and animals,including humans,fail to voluntarily modify limb trajectory to step over an obstacle.Therefore,in this review,we discuss the neuromechanical control of stepping over an obstacle,why it fails after spinal cord injury,and how it recovers to a certain extent.展开更多
基金supported by the Belle Carnell Regenerative Neurorehabilitation Fundthe National Institutes of Health(R01NS113935 to CKF)。
文摘Human spinal cord organoids(hSCOs)offer a promising platform to study neurotrauma by addressing many limitations of traditional research models.These organoids provide access to human-specific physiological and genetic mechanisms and can be derived from an individual's somatic cells(e.g.,blood or skin).This enables patient-specific paradigms for precision neurotrauma research,pa rticula rly relevant to the over 300,000 people in the United States living with chronic effects of spinal cord injury(SCI).
文摘Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.
基金funded by Natural Science Foundation of Shandong Province(Grant no.:ZR2021MH304).
文摘Spinal cord injury(SCI)refers to the impairment of neural structure and its function in spinal canal caused by various reasons,resulting in spinal cord dysfunction below the injury level.Currently,the most commonly used sensory assessment scale for individuals with SCI is the American Spinal Cord Injury Association(ASIA)score,which can quickly identify the spinal level of sensory deficit.However,the ASIA can only identify the sensory impairment in SCI as 3-level,which is not accurate expression of sensory deficit in patients with SCI.
基金supported by Craig H.Neilsen Foundation,Wings for Life Foundation,Canadian Institutes of Health Research,and Fonds de Recherche Québec-Santé(to FB).
文摘Spinal cord injury(SCI)interrupts the flow of information between the brain and the spinal cord,thus leading to a loss of sensory information and motor paralysis of the body below the lesion.Surprisingly,most SCIs are incomplete and spare supraspinal pathways,especially those located within the peripheral white matter of the spinal cord,which includes reticulospinal pathways originating from the medullary reticular formation.Whereas there is abundant literature about the motor cortex,its corticospinal pathway,and its capacity to modulate functional recovery after SCI,less is known about the medullary reticular formation and its reticulospinal pathway.
基金supported by the Fundamental Research Funds for Central Public Welfare Research Institute,No.2020CZ-5(to WS and GS)the National Natural Science Foundation of China,No.31970970(to JSR)Fundamental Research Funds for the Central Universities,No.YWF-23-YG-QB-010(to JSR)。
文摘Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface electromyography.In this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury.Eleven patients with chronic complete thoracic spinal cord injury were recruited.Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol.The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation.Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically significant.These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.
文摘Spinal cord injury(SCI) often results in permanent dysfunction of locomotion,sensation,and autonomic regulation,imposing a substantial burden on both individuals and society(Anjum et al.,2020).SCI has a complex pathophysiology:an initial primary injury(mechanical trauma,axonal disruption,and hemorrhage) is followed by a progressive secondary injury cascade that involves ischemia,neuronal loss,and inflammation.Given the challenges in achieving regeneration of the injured spinal cord,neuroprotection has been at the forefront of clinical research.
基金supported by the Irish Research Council under the Government of Ireland Postdoctoral Fellowship Project ID-GOIPD/2023/1431(to AS).
文摘Spinal cord injury(SCI)is a debilitating ailment that leads to the loss of motor and sensory functions,often leaving the patient paralyzed below the injury site(Chen et al.,2013).Globally around 250,000-300,000 people are diagnosed with SCI annually(Singh et al.,2014),and while this number appears quite low,the effect that an SCI has on the patient’s quality of life is drastic,due to the current difficulties to comprehensively treat this illness.The cost of patient care can also be quite costly,amounting to an estimated$1.69 billion in healthcare costs in the USA alone(Mahabaleshwarkar and Khanna,2014).
基金supported by the Natural Science Foundation of Fujian Province,No.2021J02035(to WX).
文摘Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.
基金supported by the NIH (R01NS103481, R01NS111776, and R01NS131489)Indiana Department of Health (ISDH58180)(all to WW)。
文摘Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.
文摘Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury–specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research(in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc(AXER-204), fasudil, phosphatase and tensin homolog protein antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide,(-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidates have been identified through basic research, and these candidates may be subjects of clinical studies in the future. Moreover, cocktail therapy comprising drugs with varied underlying mechanisms may be effective in treating the refractory status of chronic spinal cord injury.
基金supported by the National Natural Science Foundation of China,No.82202681(to JW)the Natural Science Foundation of Zhejiang Province,Nos.LZ22H090003(to QC),LR23H060001(to CL).
文摘Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they cause.Despite the ongoing development of various therapies for spinal cord injuries,their effectiveness remains unsatisfactory.However,a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming.In this review,we explore the metabolic changes that occur during spinal cord injuries,their consequences,and the therapeutic tools available for metabolic reprogramming.Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling.However,spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism,lipid metabolism,and mitochondrial dysfunction.These metabolic disturbances lead to corresponding pathological changes,including the failure of axonal regeneration,the accumulation of scarring,and the activation of microglia.To rescue spinal cord injury at the metabolic level,potential metabolic reprogramming approaches have emerged,including replenishing metabolic substrates,reconstituting metabolic couplings,and targeting mitochondrial therapies to alter cell fate.The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury.To further advance the metabolic treatment of the spinal cord injury,future efforts should focus on a deeper understanding of neurometabolism,the development of more advanced metabolomics technologies,and the design of highly effective metabolic interventions.
基金supported by the Key Research Projects of Universities of Henan Province,No.21A320064 (to XS)the National Key Research and Development Program of China,No.2021YFA1201504 (to LZ)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Science,No.XDB36000000 (to CW)the National Natural Science Foundation of China,Nos.31971295,12374406 (both to LZ)。
文摘Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.
基金supported in part by NIH R01 NS100531,R01 NS103481NIH R21NS130241(to LD)+3 种基金Merit Review Award I01 BX002356,I01 BX003705 from the U.S.Department of Veterans AffairsIndiana Spinal Cord and Brain Injury Research Foundation(No.19919)Mari Hulman George Endowment Funds(to XMX)Indiana Spinal Cord&Brain Injury Research Fund from ISDH(to NKL and LD)。
文摘Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.
基金supported by the National Natural Science Foundation of China,Nos.82071387(to HT),81971172(to YW)the Natural Science Foundation of Zhejiang Province,China,No.LY22H090012(to HT)the Basic Research Project of Wenzhou City,China,No.Y20220923(to MZ)。
文摘The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.
文摘Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal regeneration.In this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor cells.Despite a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive research.This review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.
基金supported by the National Natural Science Foundation of China(Key Program),No.11932013the National Natural Science Foundation of China(General Program),No.82272255+2 种基金Armed Police Force High-Level Science and Technology Personnel ProjectThe Armed Police Force Focuses on Supporting Scientific and Technological Innovation TeamsKey Project of Tianjin Science and Technology Plan,No.20JCZDJC00570(all to XC)。
文摘Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after injury.Recent studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for treatment.This review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord injury.Additionally,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted drugs.Nevertheless,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.
文摘One serious lesion to the central nervous system is spinal cord injury (SCI). Due to its intricate pathophysiological mechanisms and the irreparability of nerve cells, conventional rehabilitation approaches often prove inadequate for achieving full recovery. Consequently, most patients can only enhance their capacity for self-care in daily activities through early and proactive rehabilitation interventions. Stem cells are a class of cells that have the capacity to differentiate and are capable of safely and effectively differentiating into various types of neurons to repair or compensate for damaged cells, thereby exerting therapeutic effects. Currently, research on stem cell-based therapeutics for SCI is actively progressing and has yielded promising results. We discussed the anatomy, pathophysiological, the potential mechanisms of traditional therapy and stem cell therapy for SCI. The types of stem cells commonly used in current research and the latest progress in spinal cord therapy are described. Hope to serve as a resource for the use of stem cells in clinical settings.
基金Wangjing Hospital Affiliated to China Academy of Chinese Medical Sciences,Grant/Award Number:WJYY-YJKT-2022-13。
文摘Background:Although decompression surgery is the optimal treatment for patients with severe degenerative cervical myelopathy(DCM),some individuals experience no improvement or even a decline in neurological function after surgery,with spinal cord ischemia–reperfusion injury(SCII)identified as the primary cause.Spinal cord compression results in local ischemia and blood perfusion following decompression is fundamental to SCII.However,owing to inadequate perioperative blood flow monitoring,direct evidence regarding the occurrence of SCII after decompression is lacking.The objective of this study was to establish a suitable animal model for investigating the underlying mechanism of spinal cord ischemia–reperfusion injury following decom-pression surgery for degenerative cervical myelopathy(DCM)and to elucidate alterations in neurological function and local blood flow within the spinal cord before and after decompression.Methods:Twenty-four Sprague–Dawley rats were allocated to three groups:the DCM group(cervical compression group,with implanted compression material in the spinal canal,n=8),the DCM-D group(cervical decompression group,with removal of compression material from the spinal canal 4 weeks after implantation,n=8),and the SHAM group(sham operation,n=8).Von Frey test,forepaw grip strength,and gait were assessed within 4 weeks post-implantation.Spinal cord compression was evaluated using magnetic resonance imaging.Local blood flow in the spinal cord was monitored during the perioperative decompression.The rats were sacrificed 1 week after decompression to observe morphological changes in the compressed or decompressed segments of the spinal cord.Additionally,NeuN expression and the oxidative damage marker 8-oxoG DNA were analyzed.Results:Following spinal cord compression,abnormal mechanical pain worsened,and a decrease in forepaw grip strength was observed within 1–4 weeks.Upon decompression,the abnormal mechanical pain subsided,and forepaw grip strength was restored;however,neither reached the level of the sham operation group.Decompression leads to an increase in the local blood flow,indicating improved perfusion of the spinal cord.The number of NeuN-positive cells in the spinal cord of rats in the DCM-D group exceeded that in the DCM group but remained lower than that in the SHAM group.Notably,a higher level of 8-oxoG DNA expression was observed,suggesting oxidative stress following spinal cord decompression.Conclusion:This model is deemed suitable for analyzing the underlying mechanism of SCII following decompressive cervical laminectomy,as we posit that the obtained results are comparable to the clinical progression of degenerative cervical myelopathy(DCM)post-decompression and exhibit analogous neurological alterations.Notably,this model revealed ischemic reperfusion in the spinal cord after decompression,concomitant with oxidative damage,which plausibly underlies the neurological deterioration observed after decompression.
基金supported by the Department of Veterans Affairs(VA Merit Award BX004256)(to AMA)Emory Department of Neurosurgery Catalyst GrantEmory Medical Care Foundation Grant(to AMA and JG)。
文摘Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this population.Following the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing research.In this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the pathology.We study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular patterns.Several effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord injury.Following this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human subjects.This review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.
文摘Every day walking consists of frequent voluntary modifications in the gait pattern to negotiate obstacles.After spinal cord injury,stepping over an obstacle becomes challenging.Stepping over an obstacle requires sensorimotor transformations in several structures of the brain,including the parietal cortex,premotor cortex,and motor cortex.Sensory information and planning are transformed into motor commands,which are sent from the motor cortex to spinal neuronal circuits to alter limb trajectory,coordinate the limbs,and maintain balance.After spinal cord injury,bidirectional communication between the brain and spinal cord is disrupted and animals,including humans,fail to voluntarily modify limb trajectory to step over an obstacle.Therefore,in this review,we discuss the neuromechanical control of stepping over an obstacle,why it fails after spinal cord injury,and how it recovers to a certain extent.
