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
The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate ne...The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.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
Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functio...Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functional recovery after brain injury.Neuromodulation technologies represent one of the fastest-growing fields in medicine.These techniques utilize electricity,magnetism,sound,and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury.Therefore,this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury.Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury.However,studies report negative findings,potentially due to variations in stimulation protocols,differences in observation periods,and the severity of functional impairments among participants across different clinical trials.Additionally,we observed that different neuromodulation techniques share remarkably similar mechanisms,including promoting neuroplasticity,enhancing neurotrophic factor release,improving cerebral blood flow,suppressing neuroinflammation,and providing neuroprotection.Finally,considering the advantages and disadvantages of various neuromodulation techniques,we propose that future development should focus on closed-loop neural circuit stimulation,personalized treatment,interdisciplinary collaboration,and precision stimulation.展开更多
Objective:To investigate the effects of performance-linked early rehabilitation management model on the recovery of neurological function,motor function and activities of daily living in patients after intracerebral h...Objective:To investigate the effects of performance-linked early rehabilitation management model on the recovery of neurological function,motor function and activities of daily living in patients after intracerebral hemorrhage surgery.Methods:A randomized controlled trial design was adopted.A total of 120 patients after cerebral hemorrhage surgery admitted to our hospital from June 2023 to June 2024 were selected as the research subjects and were randomly divided into the experimental group and the control group,with 60 cases in each group according to the random number table method.The control group received routine postoperative care and rehabilitation guidance in neurosurgery,while the experimental group implemented an efficacy linkage early rehabilitation management model on the basis of routine care.Before the intervention,4 weeks after the intervention,and 12 weeks after the intervention,the National Institutes of Health Stroke Scale(NIHSS),the Fugl-Meyer Assessment of Motor Function(FMA),and the Barthel Index(BI)were used to assess the degree of neurological deficits,motor function,and activities of daily living in patients,respectively.Results:After 4 weeks and 12 weeks of intervention,the NIHSS scores of the experimental group[(8.5±2.1)points,(5.2±1.8)points]were significantly lower than those of the control group[(10.8±2.4)points,(7.9±2.2)points](P<0.01);FMA scores[(58.4±10.2)points,(78.6±12.4)points]and BI scores[(55.3±11.5)points,(72.8±13.2)points]were significantly higher than those of the control group[(45.2±9.8)points,(62.3±11.7)points;(42.1±10.6)points,(58.4±12.5)points](P<0.01).Conclusion:The performance-linked early rehabilitation management model can effectively promote the recovery of neurological and motor functions in patients after cerebral hemorrhage surgery and significantly improve their ability to take care of themselves in daily living.It is an efficient rehabilitation management strategy.展开更多
Objective:To investigate the positive eff ect of mindfulness training and exercise therapy on functional recovery and quality of life in elderly patients with fractures of the lower back.Methods:Collection of medical ...Objective:To investigate the positive eff ect of mindfulness training and exercise therapy on functional recovery and quality of life in elderly patients with fractures of the lower back.Methods:Collection of medical records of patients with lumbar vertebral fractures in Suzhou Municipal Hospital(North District),60 patients underwent percutaneous vertebroplasty(PVP/PKP),they were divided into control and experimental groups according to a random number table,30 people per group;In addition to traditional care method,Also intervened with behavioural awareness training and exercise therapy,By comparing the Oswestry dysfunction index score(ODI),visual simulation score(VAS),ability of daily living score(ADL),quality of life score(SF-36),To evaluate the eff ectiveness of the intervention.Results:Before the intervention,the ODI,VAS,ADL,and SF-36 scores were basically the same,with no significant diff erence(P>0.05).After treatment,the ODI and VAS scores of the experimental group and the control group were signifi cantly lower,and the experimental group was significantly lower than the control group(P<0.05);the ADL scores of the experimental group were signifi cantly higher than those of the control group(P<0.05);their SF-36 quality of life scores in all dimensions were signifi cantly higher(P<0.05).Conclusion:Through the rehabilitation treatment method combining mindfulness behavior training and exercise intervention,it can eff ectively promote the functional recovery of osteoporotic lumbar fractures in the elderly,thus reducing their pain and improving their quality of life.展开更多
BACKGROUND Total knee arthroplasty(TKA)aims to restore motion and alleviate pain,enabling patients to return to daily activities.Despite advances in implants,surgery,and perioperative care,patient dissatisfaction rate...BACKGROUND Total knee arthroplasty(TKA)aims to restore motion and alleviate pain,enabling patients to return to daily activities.Despite advances in implants,surgery,and perioperative care,patient dissatisfaction rates remain significant.AIM To determine whether ankle symptoms are associated with inferior results of functional recovery of the knee following TKA.METHODS This prospective study included all patients with advanced knee osteoarthritis who underwent a primary unilateral TKA between August 2019 and December 2019 with data documented by the treating surgeon and outpatient physical therapists.Patients were categorized based on ankle symptoms using the Ame-rican Orthopaedic Foot and Ankle Society(AOFAS)score:(1)Group 1(AOFAS≤85,n=30);and(2)Group 2(AOFAS>85,n=49).Active range of motion(ROM),the Knee Injury and Osteoarthritis Outcome Score(KOOS),and the visual ana-logue scale(VAS)were compared between two groups.RESULTS Postoperative KOOS,ROM,and VAS significantly improved in both groups(P<0.001).However,at three months,KOOS(P=0.02)and extension motion(P=0.01)improvements were significantly greater in group 2.CONCLUSION These findings suggest that preoperative ankle symptoms may negatively impact early knee functional recovery,particularly in KOOS scores and extension motion.展开更多
Quantifying the post-earthquake functional recovery of railway stations presents significant challenges.This paper first establishes a post-earthquake function calculation method for railway stations,encompassing the ...Quantifying the post-earthquake functional recovery of railway stations presents significant challenges.This paper first establishes a post-earthquake function calculation method for railway stations,encompassing the establishment of relationships between the station’s function and the damage state,function loss,and failure probability of components and professional equipment in each layer.Also,the“4 stages-6 sequences”post-earthquake repair method is present,taking into account the functional and structural characteristics of railway stations.Additionally,a novel piecewise function for the post-earthquake functional dynamic recovery of railway stations is developed.A case study is conducted on a typical railway station to demonstrate the analysis procedure.Results indicate that under fortification,rare,and extremely rare earthquake scenarios,the interlayer drift ratio(IDR)of the railway station were 1/276,1/143,and 1/52,respectively,and corresponding peak floor acceleration(PFA)were 6.31 m/s^(2),7.82 m/s^(2),and 8.57 m/s^(2),respectively.The post-earthquake function of the railway station was 93.21%,82.33%,and 64.16%of its initial function.The repair times were 6.66 days,18.65 days,and 37.42 days.The displacement-sensitive,non-structural components were identified as the most vulnerable to damage.And the first repair stage(R_(1))which was mainly used to repair structural components and non-structural transport components,accounted for the highest proportion of total repair time.展开更多
Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells a...Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.展开更多
Background: In Japan, due to the COVID-19 pandemic, various behavioral restrictions were implemented from March 2020, resulting in an increased number of elderly people with reduced participation in care and rehabilit...Background: In Japan, due to the COVID-19 pandemic, various behavioral restrictions were implemented from March 2020, resulting in an increased number of elderly people with reduced participation in care and rehabilitation. As a result, the decline in motor and cognitive functions became more pronounced. Purpose: The study examined how activities combining passive horticultural therapy, which is always introduced, with active functional recovery training, which is used in the functional recovery training of patients with hemiplegia, influence the behavior of elder people using the facility. Methods: 36 elder people with care need 1 or 2 who regularly used the day-care facilities after the pandemic ended and who agreed to participate in the study was included. The assessment data were every three months from December 2021 to December 2023 after the COVID-19 pandemic, the MMSE and Moca-J, TMIG-Index, and GDS15. AI-based text mining was used to compare changes in visit reports before and after the introduction of the Posture Chart and Red Code, and the relationship between the language used. Results: The results of MMSE and Moca-J were both significantly higher in Group B and C than in Group A. TIMG assessment, was significantly higher in Group B and C than in Group A, and Group C was significantly higher than Group B. The GDS, an assessment of depression in old age, tended to be significantly higher in Group A than in Groups B and C. In the “Co-Occurrence Network Analysis” shown after the introduction of the latest functional recovery training equipment such as the Red Cord, its results showed a high association between the words Bathing and CARE and words such as POSTURE, Red-Code, and AI, App, which are used in functional training and rehabilitation, and their analysis. Conclusion: At day-care facilities specializing in functional recovery training and rehabilitation, a combination of horticultural therapy and the latest functional training equipment found to help maintain the physical and mental health of elderly people certified as requiring nursing care. Since this is a short-term study following behavioral restrictions, long-term research should continue to study the effects of adding functional training, handled by rehabilitation professionals, to horticultural therapy.展开更多
Objective Combine olfactory ensheathing glia (OEG) implantation with ex vivo non-viral vector-based neurotrophin- 3 (NT-3) gene therapy in attempting to enhance regeneration after thoracic spinal cord injury (SCI...Objective Combine olfactory ensheathing glia (OEG) implantation with ex vivo non-viral vector-based neurotrophin- 3 (NT-3) gene therapy in attempting to enhance regeneration after thoracic spinal cord injury (SCI). Methods Primary OEG were transfected with cationic liposome-mediated recombinant plasmid pcDNA3.1 (+)-NT3 and subsequently implanted into adult Wistar rats directly after the thoracic spinal cord (T9) contusion by the New York University impactor. The animals in 3 different groups received 4x 1050EG transfected with pcDNA3.1 (+)-NT3 or pcDNA3.1 (+) plasmids, or the OEGs without any plasmid transfection, respectively; the fourth group was untreated group, in which no OEG was implanted. Results NT-3 production was seen increased both ex vivo and in vivo in pcDNA3.1 (+)-NT3 transfected OEGs. Three months after implantation of NT-3-transfected OEGs, behavioral analysis revealed that the hindlimb function of SCI rats was improved. All spinal cords were filled with regenerated neurofilament-positive axons. Retrograde tracing revealed enhanced regenerative axonal sprouting. Conclusion Non-viral vector-mediated genetic engineering of OEG was safe and more effective in producing NT- 3 and promoting axonal outgrowth followed by enhancing SCI recovery in rats.展开更多
A hyaluronic acid granular hydrogel can promote neuronal and astrocyte colony formation and axonal extension in vitro,suggesting that the hydrogel can simulate an extracellular matrix structure to promote neural regen...A hyaluronic acid granular hydrogel can promote neuronal and astrocyte colony formation and axonal extension in vitro,suggesting that the hydrogel can simulate an extracellular matrix structure to promote neural regeneration.However,in vivo experiments have not been conducted.In this study,we transplanted a hyaluronic acid granular hydrogel nerve guidance conduit to repair a 10-mm long sciatic nerve gap.The Basso,Beattie,and Bresnahan locomotor rating scale,sciatic nerve compound muscle action potential recording,Fluoro-Gold retrograde tracing,growth related protein 43/S100 immunofluorescence staining,transmission electron microscopy,gastrocnemius muscle dry/wet weight ratio,and Masson’s trichrome staining results showed that the nerve guidance conduit exhibited similar regeneration of sciatic nerve axons and myelin sheath,and recovery of the electrophysiological function and motor function as autologous nerve transplantation.The conduit results were superior to those of a bulk hydrogel or silicone tube transplant.These findings suggest that tissue-engineered nerve conduits containing hyaluronic acid granular hydrogels effectively promote the morphological and functional recovery of the injured sciatic nerve.The nerve conduits have the potential as a material for repairing peripheral nerve defects.展开更多
Medialization thyroplasty or injection laryngoplasty for unilateral vocal fold paralysis cannot restore mobility of the vocal fold. Recent studies have shown that transplantation of mesenchymal stem cells is effective...Medialization thyroplasty or injection laryngoplasty for unilateral vocal fold paralysis cannot restore mobility of the vocal fold. Recent studies have shown that transplantation of mesenchymal stem cells is effective in the repair of nerve injuries. This study investigated wheth- er adipose-derived stem celt transplantation could repair recurrent laryngeal nerve injury. Rat models of recurrent laryngeal nerve injury were established by crushing with micro forceps. Adipose-derived mesenchymal stem cells (ADSCs; 8 ×105) or differentiated Schwann-like adipose-derived mesenchymal stem cells (dADSCs; 8×105) or extracellular matrix were injected at the site of injury. At 2, 4 and 6 weeks post-surgery, a higher density of myelinated nerve fiber, thicker myelin sheath, improved vocal fold movement, better recovery of nerve conduction capacity and reduced thyroarytenoid muscle atrophy were found in ADSCs and dADSCs groups compared with the extracellu- lar matrix group. The effects were more pronounced in the ADSCs group than in the dADSCs group. These experimental results indicated that ADSCs transplantation could be an early interventional strategy to promote regeneration after recurrent laryngeal nerve injury.展开更多
Complex tibial plateau fractures can seriously affect quality of life and physical and mental health of patients.The anatomical relationship between the proximal tibial bone and soft tissue is complex,resulting in dif...Complex tibial plateau fractures can seriously affect quality of life and physical and mental health of patients.The anatomical relationship between the proximal tibial bone and soft tissue is complex,resulting in different types of tibial plateau fractures.Violent trauma can lead to displaced fracture,serious soft tissue injury,and potentially,dislocation of the knee joint.Therefore,tibial plateau fractures are extremely unstable.AIM To assess the use of locking compression plate(LCP)+T-type steel plate for postoperative weight bearing and functional recovery of complex tibial plateau fractures.METHODS Ninety-seven patients with complex tibial plateau fractures who underwent surgery at our hospital were selected for retrospective study.Forty-nine patients had been treated with LCP+T-type steel plate limited internal fixation(study group),and 48 patients with bilateral ordinary steel plate support(control group).The operation process index,postoperative rehabilitation related index,Rasmussen score of the knee joint,tibial plateau varus angle(TPA),tibial plateau retroversion angle(PA),and surgical complications of the two groups were compared.RESULTS The operation time and intraoperative bone graft volume in the study group were lower than those in the control group(P<0.05).There were no significant differences in surgical bleeding,anterior external incision length,postoperative drainage,hospital stay duration,and fracture healing time between the groups(P>0.05).There was no significant difference in the TPA and PA angle between the groups immediately and 18 mo after surgery(P>0.05).At 12 mo after surgery,the Rasmussen scale score was higher in the study group than in the control group(P<0.05).There was no significant difference in the Rasmussen scale score at 18 mo after surgery,and the radiology score at 12 and 18 mo after surgery,between the two groups(P>0.05).The postoperative complication rate in the study group(3.77%)was lower than that in the control group(15.09%;P<0.05).CONCLUSION LCP+T-type steel plate internal fixation has advantages in terms of minimizing trauma and enabling early postoperative functional exercise,promoting functional recovery and lower limb weight-bearing,and reducing postoperative complications.展开更多
Our previous RNA sequencing study showed that the long non-coding RNA ischemia-related factor Vof-16(lncRNA Vof-16)was upregulated after spinal cord injury,but its precise role in spinal cord injury remains unclear.Bi...Our previous RNA sequencing study showed that the long non-coding RNA ischemia-related factor Vof-16(lncRNA Vof-16)was upregulated after spinal cord injury,but its precise role in spinal cord injury remains unclear.Bioinformatics predictions have indicated that lncRNA Vof-16 may participate in the pathophysiological processes of inflammation and apoptosis.PC12 cells were transfected with a pHBLV-U6-MCS-CMV-ZsGreen-PGK-PURO vector to express an lncRNA Vof-16 knockdown lentivirus and a pHLV-CMVIE-ZsGree-Puro vector to express an lncRNA Vof-16 overexpression lentivirus.The overexpression of lncRNA Vof-16 inhibited PC12 cell survival,proliferation,migration,and neurite extension,whereas lncRNA Vof-16 knockdown lentiviral vector resulted in the opposite effects in PC12 cells.Western blot assay results showed that the overexpression of lncRNA Vof-16 increased the protein expression levels of interleukin 6,tumor necrosis factor-α,and Caspase-3 and decreased Bcl-2 expression levels in PC12 cells.Furthermore,we established rat models of spinal cord injury using the complete transection at T10.Spinal cord injury model rats were injected with the lncRNA Vof-16 knockdown or overexpression lentiviral vectors immediately after injury.At 7 days after spinal cord injury,rats treated with lncRNA Vof-16 knockdown displayed increased neuronal survival and enhanced axonal extension.At 8 weeks after spinal cord injury,rats treated with the lncRNA Vof-16 knockdown lentiviral vector displayed improved neurological function in the hind limb.Notably,lncRNA Vof-16 knockdown injection increased Bcl-2 expression and decreased tumor necrosis factor-αand Caspase-3 expression in treated animals.Rats treated with the lncRNA Vof-16 overexpression lentiviral vector displayed opposite trends.These findings suggested that lncRNA Vof-16 is associated with the regulation of inflammation and apoptosis.The inhibition of lncRNA Vof-16 may be useful for promoting nerve regeneration and functional recovery after spinal cord injury.The experiments were approved by the Institutional Animal Care and Use Committee of Guangdong Medical University,China.展开更多
Studies have shown that exercise interventions can improve functional recovery after spinal cord injury, but the mechanism of action remains unclear. To investigate the mechanism, we estab-lished a unilateral corticos...Studies have shown that exercise interventions can improve functional recovery after spinal cord injury, but the mechanism of action remains unclear. To investigate the mechanism, we estab-lished a unilateral corticospinal tract injury model in rats by pyramidotomy, and used a single pellet reaching task and horizontal ladder walking task as exercise interventions postoperatively. Functional recovery of forelimbs and forepaws in the rat models was noticeably enhanced after the exercises. Furthermore, TUNEL staining revealed signiifcantly fewer apoptotic cells in the spinal cord of exercised rats, and western blot analysis showed that spinal cord expression of the apopto-sis-related protein caspase-3 was signiifcantly lower, and the expression of Bcl-2 was signiifcantly higher, while the expression of Bax was not signiifantly changed after exercise, compared with the non-exercised group. Expression of these proteins decreased with time after injury, towards the levels observed in sham-operated rats, however at 4 weeks postoperatively, caspase-3 expression remained signiifcantly greater than in sham-operated rats. The present ifndings indicate that a re-duction in apoptosis is one of the mechanisms underlying the improvement of functional recovery by exercise interventions after corticospinal tract injury.展开更多
Conflicting findings exist regarding the link between functional recovery and the regrowth of spinal tracts across the lesion leading to the restoration of functional contacts. In the present study, we investigated wh...Conflicting findings exist regarding the link between functional recovery and the regrowth of spinal tracts across the lesion leading to the restoration of functional contacts. In the present study, we investigated whether functional locomotor recovery was attributable to anatomical regeneration at postnatal day 1 (PN1), PN7, PN14 and in adult rats two months after transection injury at the tenth thoracic segment of the spinal cord. The Basso, Beattie, and Bresnahan scores showed that transection led to a failure of hindlimb locomotor function in PN14 and adult rats. However, PN1 and PN7 rats showed a significant level of stepping function after complete spinal cord transection. Unexpectedly, unlike the transected PN14 and adult rats in which the spinal cord underwent limited secondary degeneration and showed a scar at the lesion site, the rats transected at PN1 and PN7 showed massive secondary degeneration both anterograde and retrograde, leaving a 〉5-mm gap between the two stumps. Furthermore, retrograde tracing with fluorogold (FG) also showed that FG did not cross the transection site in PN1 and PN7rats as in PN14 and adult rats, and re-transection of the cord caused no apparent loss in locomotor performance in the rats transected at PN1. Thus, these three lines of evidence strongly indicated that the functional recovery after transection in neonatal rats is independent of regrowth of spinal tracts across the lesion site. Our results support the notion that the recovery of locomotor function in developing rats may be due to intrinsic adaptations in the spinal circuitry below the lesion that control hindlimb locomotor activity rather than the regrowth of spinal tracts across the lesion. The difference in secondary degeneration between neonatal and adult rats remains to be explored.展开更多
Traumatic spinal cord injury (SCI) causes motor paralysis, sensory anesthesia and autonomic dysfunction below the le- sion site and additionally some SCI patients refer neuropathic pain together with these signs and...Traumatic spinal cord injury (SCI) causes motor paralysis, sensory anesthesia and autonomic dysfunction below the le- sion site and additionally some SCI patients refer neuropathic pain together with these signs and symptoms. Clinical and experimental studies have revealed the main pathological changes of injured spinal cord implicated in all these signs and symptoms, including neuropathic pain. After few hours of traumatic SCI, it is usual to observe broken blood brain barrier with plasma and blood cells extravasation, cell necrosis, disruption of ascending and descending spinal cord pathways and increased potassium and glutamate. Glutamate contributes to excitotoxicity of neurons whereas potassium facilitates ectopic depolarization of survival neurons and activation of resident microglia.展开更多
Some evidence suggests that multiwalled carbon nanotubes can promote neuronal differentiation and growth. The present study investigated the effect of functional multiwalled carbon nanotubes (MWCNTs) on functional r...Some evidence suggests that multiwalled carbon nanotubes can promote neuronal differentiation and growth. The present study investigated the effect of functional multiwalled carbon nanotubes (MWCNTs) on functional recovery of injured sciatic nerves in mice. The results revealed that MWCNTs accelerated the recovery of functional index scores of injured sciatic nerves in mice. Moreover, the medullary sheath was significantly thicker in the injured sciatic nerve following MWCNTs administration. These effects were dose-dependent.展开更多
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.
基金supported by the National Natural Science Foundation of China,Nos.82272171(to ZY),82271403(to XL),81941011(to XL),31971279(to ZY),31730030(to XL)the Natural Science Foundation of Beijing,No.7222004(to HD).
文摘The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.
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 National Natural Science Foundation of China,No.82371399(to YY)the Natural Science Foundation of Jiangsu Province,No.BK20221206(to YY)+1 种基金the Young Elite Scientists Sponsorship Program of Jiangsu Province,No.TJ-2022-028(to YY)the Scientific Research Program of Wuxi Health Commission,No.Z202302(to LY)。
文摘Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functional recovery after brain injury.Neuromodulation technologies represent one of the fastest-growing fields in medicine.These techniques utilize electricity,magnetism,sound,and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury.Therefore,this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury.Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury.However,studies report negative findings,potentially due to variations in stimulation protocols,differences in observation periods,and the severity of functional impairments among participants across different clinical trials.Additionally,we observed that different neuromodulation techniques share remarkably similar mechanisms,including promoting neuroplasticity,enhancing neurotrophic factor release,improving cerebral blood flow,suppressing neuroinflammation,and providing neuroprotection.Finally,considering the advantages and disadvantages of various neuromodulation techniques,we propose that future development should focus on closed-loop neural circuit stimulation,personalized treatment,interdisciplinary collaboration,and precision stimulation.
文摘Objective:To investigate the effects of performance-linked early rehabilitation management model on the recovery of neurological function,motor function and activities of daily living in patients after intracerebral hemorrhage surgery.Methods:A randomized controlled trial design was adopted.A total of 120 patients after cerebral hemorrhage surgery admitted to our hospital from June 2023 to June 2024 were selected as the research subjects and were randomly divided into the experimental group and the control group,with 60 cases in each group according to the random number table method.The control group received routine postoperative care and rehabilitation guidance in neurosurgery,while the experimental group implemented an efficacy linkage early rehabilitation management model on the basis of routine care.Before the intervention,4 weeks after the intervention,and 12 weeks after the intervention,the National Institutes of Health Stroke Scale(NIHSS),the Fugl-Meyer Assessment of Motor Function(FMA),and the Barthel Index(BI)were used to assess the degree of neurological deficits,motor function,and activities of daily living in patients,respectively.Results:After 4 weeks and 12 weeks of intervention,the NIHSS scores of the experimental group[(8.5±2.1)points,(5.2±1.8)points]were significantly lower than those of the control group[(10.8±2.4)points,(7.9±2.2)points](P<0.01);FMA scores[(58.4±10.2)points,(78.6±12.4)points]and BI scores[(55.3±11.5)points,(72.8±13.2)points]were significantly higher than those of the control group[(45.2±9.8)points,(62.3±11.7)points;(42.1±10.6)points,(58.4±12.5)points](P<0.01).Conclusion:The performance-linked early rehabilitation management model can effectively promote the recovery of neurological and motor functions in patients after cerebral hemorrhage surgery and significantly improve their ability to take care of themselves in daily living.It is an efficient rehabilitation management strategy.
文摘Objective:To investigate the positive eff ect of mindfulness training and exercise therapy on functional recovery and quality of life in elderly patients with fractures of the lower back.Methods:Collection of medical records of patients with lumbar vertebral fractures in Suzhou Municipal Hospital(North District),60 patients underwent percutaneous vertebroplasty(PVP/PKP),they were divided into control and experimental groups according to a random number table,30 people per group;In addition to traditional care method,Also intervened with behavioural awareness training and exercise therapy,By comparing the Oswestry dysfunction index score(ODI),visual simulation score(VAS),ability of daily living score(ADL),quality of life score(SF-36),To evaluate the eff ectiveness of the intervention.Results:Before the intervention,the ODI,VAS,ADL,and SF-36 scores were basically the same,with no significant diff erence(P>0.05).After treatment,the ODI and VAS scores of the experimental group and the control group were signifi cantly lower,and the experimental group was significantly lower than the control group(P<0.05);the ADL scores of the experimental group were signifi cantly higher than those of the control group(P<0.05);their SF-36 quality of life scores in all dimensions were signifi cantly higher(P<0.05).Conclusion:Through the rehabilitation treatment method combining mindfulness behavior training and exercise intervention,it can eff ectively promote the functional recovery of osteoporotic lumbar fractures in the elderly,thus reducing their pain and improving their quality of life.
文摘BACKGROUND Total knee arthroplasty(TKA)aims to restore motion and alleviate pain,enabling patients to return to daily activities.Despite advances in implants,surgery,and perioperative care,patient dissatisfaction rates remain significant.AIM To determine whether ankle symptoms are associated with inferior results of functional recovery of the knee following TKA.METHODS This prospective study included all patients with advanced knee osteoarthritis who underwent a primary unilateral TKA between August 2019 and December 2019 with data documented by the treating surgeon and outpatient physical therapists.Patients were categorized based on ankle symptoms using the Ame-rican Orthopaedic Foot and Ankle Society(AOFAS)score:(1)Group 1(AOFAS≤85,n=30);and(2)Group 2(AOFAS>85,n=49).Active range of motion(ROM),the Knee Injury and Osteoarthritis Outcome Score(KOOS),and the visual ana-logue scale(VAS)were compared between two groups.RESULTS Postoperative KOOS,ROM,and VAS significantly improved in both groups(P<0.001).However,at three months,KOOS(P=0.02)and extension motion(P=0.01)improvements were significantly greater in group 2.CONCLUSION These findings suggest that preoperative ankle symptoms may negatively impact early knee functional recovery,particularly in KOOS scores and extension motion.
基金National Natural Science Foundation of China under Grant No.52278534the Sichuan Provincial Natural Science Foundation of China under Grant No.2022NSFSC0423。
文摘Quantifying the post-earthquake functional recovery of railway stations presents significant challenges.This paper first establishes a post-earthquake function calculation method for railway stations,encompassing the establishment of relationships between the station’s function and the damage state,function loss,and failure probability of components and professional equipment in each layer.Also,the“4 stages-6 sequences”post-earthquake repair method is present,taking into account the functional and structural characteristics of railway stations.Additionally,a novel piecewise function for the post-earthquake functional dynamic recovery of railway stations is developed.A case study is conducted on a typical railway station to demonstrate the analysis procedure.Results indicate that under fortification,rare,and extremely rare earthquake scenarios,the interlayer drift ratio(IDR)of the railway station were 1/276,1/143,and 1/52,respectively,and corresponding peak floor acceleration(PFA)were 6.31 m/s^(2),7.82 m/s^(2),and 8.57 m/s^(2),respectively.The post-earthquake function of the railway station was 93.21%,82.33%,and 64.16%of its initial function.The repair times were 6.66 days,18.65 days,and 37.42 days.The displacement-sensitive,non-structural components were identified as the most vulnerable to damage.And the first repair stage(R_(1))which was mainly used to repair structural components and non-structural transport components,accounted for the highest proportion of total repair time.
基金supported by the Stem Cell and Translation National Key Project,No.2016YFA0101403(to ZC)the National Natural Science Foundation of China,Nos.82171250 and 81973351(to ZC)+6 种基金the Natural Science Foundation of Beijing,No.5142005(to ZC)Beijing Talents Foundation,No.2017000021223TD03(to ZC)Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan,No.CIT&TCD20180333(to ZC)Beijing Municipal Health Commission Fund,No.PXM2020_026283_000005(to ZC)Beijing One Hundred,Thousand,and Ten Thousand Talents Fund,No.2018A03(to ZC)the Royal Society-Newton Advanced Fellowship,No.NA150482(to ZC)the National Natural Science Foundation of China for Young Scientists,No.31900740(to SL)。
文摘Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.
文摘Background: In Japan, due to the COVID-19 pandemic, various behavioral restrictions were implemented from March 2020, resulting in an increased number of elderly people with reduced participation in care and rehabilitation. As a result, the decline in motor and cognitive functions became more pronounced. Purpose: The study examined how activities combining passive horticultural therapy, which is always introduced, with active functional recovery training, which is used in the functional recovery training of patients with hemiplegia, influence the behavior of elder people using the facility. Methods: 36 elder people with care need 1 or 2 who regularly used the day-care facilities after the pandemic ended and who agreed to participate in the study was included. The assessment data were every three months from December 2021 to December 2023 after the COVID-19 pandemic, the MMSE and Moca-J, TMIG-Index, and GDS15. AI-based text mining was used to compare changes in visit reports before and after the introduction of the Posture Chart and Red Code, and the relationship between the language used. Results: The results of MMSE and Moca-J were both significantly higher in Group B and C than in Group A. TIMG assessment, was significantly higher in Group B and C than in Group A, and Group C was significantly higher than Group B. The GDS, an assessment of depression in old age, tended to be significantly higher in Group A than in Groups B and C. In the “Co-Occurrence Network Analysis” shown after the introduction of the latest functional recovery training equipment such as the Red Cord, its results showed a high association between the words Bathing and CARE and words such as POSTURE, Red-Code, and AI, App, which are used in functional training and rehabilitation, and their analysis. Conclusion: At day-care facilities specializing in functional recovery training and rehabilitation, a combination of horticultural therapy and the latest functional training equipment found to help maintain the physical and mental health of elderly people certified as requiring nursing care. Since this is a short-term study following behavioral restrictions, long-term research should continue to study the effects of adding functional training, handled by rehabilitation professionals, to horticultural therapy.
文摘Objective Combine olfactory ensheathing glia (OEG) implantation with ex vivo non-viral vector-based neurotrophin- 3 (NT-3) gene therapy in attempting to enhance regeneration after thoracic spinal cord injury (SCI). Methods Primary OEG were transfected with cationic liposome-mediated recombinant plasmid pcDNA3.1 (+)-NT3 and subsequently implanted into adult Wistar rats directly after the thoracic spinal cord (T9) contusion by the New York University impactor. The animals in 3 different groups received 4x 1050EG transfected with pcDNA3.1 (+)-NT3 or pcDNA3.1 (+) plasmids, or the OEGs without any plasmid transfection, respectively; the fourth group was untreated group, in which no OEG was implanted. Results NT-3 production was seen increased both ex vivo and in vivo in pcDNA3.1 (+)-NT3 transfected OEGs. Three months after implantation of NT-3-transfected OEGs, behavioral analysis revealed that the hindlimb function of SCI rats was improved. All spinal cords were filled with regenerated neurofilament-positive axons. Retrograde tracing revealed enhanced regenerative axonal sprouting. Conclusion Non-viral vector-mediated genetic engineering of OEG was safe and more effective in producing NT- 3 and promoting axonal outgrowth followed by enhancing SCI recovery in rats.
基金supported by the National Natural Science Foundation of China,Nos.81620108008(to YQL),31971112(to YQL),82071373(to JC)Innovation Capability Support Program of Shaanxi,No.2021TD-57(to YQL)。
文摘A hyaluronic acid granular hydrogel can promote neuronal and astrocyte colony formation and axonal extension in vitro,suggesting that the hydrogel can simulate an extracellular matrix structure to promote neural regeneration.However,in vivo experiments have not been conducted.In this study,we transplanted a hyaluronic acid granular hydrogel nerve guidance conduit to repair a 10-mm long sciatic nerve gap.The Basso,Beattie,and Bresnahan locomotor rating scale,sciatic nerve compound muscle action potential recording,Fluoro-Gold retrograde tracing,growth related protein 43/S100 immunofluorescence staining,transmission electron microscopy,gastrocnemius muscle dry/wet weight ratio,and Masson’s trichrome staining results showed that the nerve guidance conduit exhibited similar regeneration of sciatic nerve axons and myelin sheath,and recovery of the electrophysiological function and motor function as autologous nerve transplantation.The conduit results were superior to those of a bulk hydrogel or silicone tube transplant.These findings suggest that tissue-engineered nerve conduits containing hyaluronic acid granular hydrogels effectively promote the morphological and functional recovery of the injured sciatic nerve.The nerve conduits have the potential as a material for repairing peripheral nerve defects.
基金supported by the National Natural Science Foundation of China,No.81470680,81170901the Natural Science Foundation of Beijing of China,No.7132053the Beijing Health Foundation of High-level Technical Personnel in China,No.2014-2-004
文摘Medialization thyroplasty or injection laryngoplasty for unilateral vocal fold paralysis cannot restore mobility of the vocal fold. Recent studies have shown that transplantation of mesenchymal stem cells is effective in the repair of nerve injuries. This study investigated wheth- er adipose-derived stem celt transplantation could repair recurrent laryngeal nerve injury. Rat models of recurrent laryngeal nerve injury were established by crushing with micro forceps. Adipose-derived mesenchymal stem cells (ADSCs; 8 ×105) or differentiated Schwann-like adipose-derived mesenchymal stem cells (dADSCs; 8×105) or extracellular matrix were injected at the site of injury. At 2, 4 and 6 weeks post-surgery, a higher density of myelinated nerve fiber, thicker myelin sheath, improved vocal fold movement, better recovery of nerve conduction capacity and reduced thyroarytenoid muscle atrophy were found in ADSCs and dADSCs groups compared with the extracellu- lar matrix group. The effects were more pronounced in the ADSCs group than in the dADSCs group. These experimental results indicated that ADSCs transplantation could be an early interventional strategy to promote regeneration after recurrent laryngeal nerve injury.
文摘Complex tibial plateau fractures can seriously affect quality of life and physical and mental health of patients.The anatomical relationship between the proximal tibial bone and soft tissue is complex,resulting in different types of tibial plateau fractures.Violent trauma can lead to displaced fracture,serious soft tissue injury,and potentially,dislocation of the knee joint.Therefore,tibial plateau fractures are extremely unstable.AIM To assess the use of locking compression plate(LCP)+T-type steel plate for postoperative weight bearing and functional recovery of complex tibial plateau fractures.METHODS Ninety-seven patients with complex tibial plateau fractures who underwent surgery at our hospital were selected for retrospective study.Forty-nine patients had been treated with LCP+T-type steel plate limited internal fixation(study group),and 48 patients with bilateral ordinary steel plate support(control group).The operation process index,postoperative rehabilitation related index,Rasmussen score of the knee joint,tibial plateau varus angle(TPA),tibial plateau retroversion angle(PA),and surgical complications of the two groups were compared.RESULTS The operation time and intraoperative bone graft volume in the study group were lower than those in the control group(P<0.05).There were no significant differences in surgical bleeding,anterior external incision length,postoperative drainage,hospital stay duration,and fracture healing time between the groups(P>0.05).There was no significant difference in the TPA and PA angle between the groups immediately and 18 mo after surgery(P>0.05).At 12 mo after surgery,the Rasmussen scale score was higher in the study group than in the control group(P<0.05).There was no significant difference in the Rasmussen scale score at 18 mo after surgery,and the radiology score at 12 and 18 mo after surgery,between the two groups(P>0.05).The postoperative complication rate in the study group(3.77%)was lower than that in the control group(15.09%;P<0.05).CONCLUSION LCP+T-type steel plate internal fixation has advantages in terms of minimizing trauma and enabling early postoperative functional exercise,promoting functional recovery and lower limb weight-bearing,and reducing postoperative complications.
基金financially supported by the National Natural Science Foundation of China,No.82071374(to HFW)Characteristic Innovation Project of Colleges and Universities in Guangdong Province of China,No.2018KTSCX075(to HFW)+5 种基金the Key Project of Social Development of Dongguan of China,No.20185071521640(to HFW)College Students Science and Technology Innovation Cultivation Project in Guangdong of China,Nos.pdjh2020b0257(to HFW),pdjh2020b0263(to HFW)College Students Innovative Experimental Project in Guangdong Medical University,China,Nos.ZZDS006(to HFW),ZYDS005(to HFW),ZYDB004(to HFW),FYDY003(to HFW)College Students’Science and Technology Innovation Training Project,Nos.202010571027(to HFW),202010571054(to HFW),202010571055(to HFW),202010571084(to HFW),202010571099(to HFW),GDMU2019054(to HFW)GDMU2019055(to HFW),GDMU2019099,GDMU2019123(to HFW),GDMU2019027(to HFW),GDMU2019084(to HFW)the Scientific and Technological Projects of Dongguan City,No.202050715023190(to WJF)。
文摘Our previous RNA sequencing study showed that the long non-coding RNA ischemia-related factor Vof-16(lncRNA Vof-16)was upregulated after spinal cord injury,but its precise role in spinal cord injury remains unclear.Bioinformatics predictions have indicated that lncRNA Vof-16 may participate in the pathophysiological processes of inflammation and apoptosis.PC12 cells were transfected with a pHBLV-U6-MCS-CMV-ZsGreen-PGK-PURO vector to express an lncRNA Vof-16 knockdown lentivirus and a pHLV-CMVIE-ZsGree-Puro vector to express an lncRNA Vof-16 overexpression lentivirus.The overexpression of lncRNA Vof-16 inhibited PC12 cell survival,proliferation,migration,and neurite extension,whereas lncRNA Vof-16 knockdown lentiviral vector resulted in the opposite effects in PC12 cells.Western blot assay results showed that the overexpression of lncRNA Vof-16 increased the protein expression levels of interleukin 6,tumor necrosis factor-α,and Caspase-3 and decreased Bcl-2 expression levels in PC12 cells.Furthermore,we established rat models of spinal cord injury using the complete transection at T10.Spinal cord injury model rats were injected with the lncRNA Vof-16 knockdown or overexpression lentiviral vectors immediately after injury.At 7 days after spinal cord injury,rats treated with lncRNA Vof-16 knockdown displayed increased neuronal survival and enhanced axonal extension.At 8 weeks after spinal cord injury,rats treated with the lncRNA Vof-16 knockdown lentiviral vector displayed improved neurological function in the hind limb.Notably,lncRNA Vof-16 knockdown injection increased Bcl-2 expression and decreased tumor necrosis factor-αand Caspase-3 expression in treated animals.Rats treated with the lncRNA Vof-16 overexpression lentiviral vector displayed opposite trends.These findings suggested that lncRNA Vof-16 is associated with the regulation of inflammation and apoptosis.The inhibition of lncRNA Vof-16 may be useful for promoting nerve regeneration and functional recovery after spinal cord injury.The experiments were approved by the Institutional Animal Care and Use Committee of Guangdong Medical University,China.
基金financially supported by the National Natural Science Foundation of China,No.81350013
文摘Studies have shown that exercise interventions can improve functional recovery after spinal cord injury, but the mechanism of action remains unclear. To investigate the mechanism, we estab-lished a unilateral corticospinal tract injury model in rats by pyramidotomy, and used a single pellet reaching task and horizontal ladder walking task as exercise interventions postoperatively. Functional recovery of forelimbs and forepaws in the rat models was noticeably enhanced after the exercises. Furthermore, TUNEL staining revealed signiifcantly fewer apoptotic cells in the spinal cord of exercised rats, and western blot analysis showed that spinal cord expression of the apopto-sis-related protein caspase-3 was signiifcantly lower, and the expression of Bcl-2 was signiifcantly higher, while the expression of Bax was not signiifantly changed after exercise, compared with the non-exercised group. Expression of these proteins decreased with time after injury, towards the levels observed in sham-operated rats, however at 4 weeks postoperatively, caspase-3 expression remained signiifcantly greater than in sham-operated rats. The present ifndings indicate that a re-duction in apoptosis is one of the mechanisms underlying the improvement of functional recovery by exercise interventions after corticospinal tract injury.
基金supported by the Hong Kong SCI Fundthe National Basic Research Development Program (973 program) of China (2011CB504402)
文摘Conflicting findings exist regarding the link between functional recovery and the regrowth of spinal tracts across the lesion leading to the restoration of functional contacts. In the present study, we investigated whether functional locomotor recovery was attributable to anatomical regeneration at postnatal day 1 (PN1), PN7, PN14 and in adult rats two months after transection injury at the tenth thoracic segment of the spinal cord. The Basso, Beattie, and Bresnahan scores showed that transection led to a failure of hindlimb locomotor function in PN14 and adult rats. However, PN1 and PN7 rats showed a significant level of stepping function after complete spinal cord transection. Unexpectedly, unlike the transected PN14 and adult rats in which the spinal cord underwent limited secondary degeneration and showed a scar at the lesion site, the rats transected at PN1 and PN7 showed massive secondary degeneration both anterograde and retrograde, leaving a 〉5-mm gap between the two stumps. Furthermore, retrograde tracing with fluorogold (FG) also showed that FG did not cross the transection site in PN1 and PN7rats as in PN14 and adult rats, and re-transection of the cord caused no apparent loss in locomotor performance in the rats transected at PN1. Thus, these three lines of evidence strongly indicated that the functional recovery after transection in neonatal rats is independent of regrowth of spinal tracts across the lesion site. Our results support the notion that the recovery of locomotor function in developing rats may be due to intrinsic adaptations in the spinal circuitry below the lesion that control hindlimb locomotor activity rather than the regrowth of spinal tracts across the lesion. The difference in secondary degeneration between neonatal and adult rats remains to be explored.
基金funded by Accions Singulars de R+D(Sing 12/17)del Vicerectorat de Recerca de la Universitat de Girona,Girona,Spain
文摘Traumatic spinal cord injury (SCI) causes motor paralysis, sensory anesthesia and autonomic dysfunction below the le- sion site and additionally some SCI patients refer neuropathic pain together with these signs and symptoms. Clinical and experimental studies have revealed the main pathological changes of injured spinal cord implicated in all these signs and symptoms, including neuropathic pain. After few hours of traumatic SCI, it is usual to observe broken blood brain barrier with plasma and blood cells extravasation, cell necrosis, disruption of ascending and descending spinal cord pathways and increased potassium and glutamate. Glutamate contributes to excitotoxicity of neurons whereas potassium facilitates ectopic depolarization of survival neurons and activation of resident microglia.
基金Science and Technology Key Program of Anhui Province in 2007, No. 07010300199
文摘Some evidence suggests that multiwalled carbon nanotubes can promote neuronal differentiation and growth. The present study investigated the effect of functional multiwalled carbon nanotubes (MWCNTs) on functional recovery of injured sciatic nerves in mice. The results revealed that MWCNTs accelerated the recovery of functional index scores of injured sciatic nerves in mice. Moreover, the medullary sheath was significantly thicker in the injured sciatic nerve following MWCNTs administration. These effects were dose-dependent.