Axonal junction defects and an inhibitory environment after spinal cord injury seriously hinder the regeneration of damaged tissues and neuronal functions. At the site of spinal cord injury, regenerative biomaterials ...Axonal junction defects and an inhibitory environment after spinal cord injury seriously hinder the regeneration of damaged tissues and neuronal functions. At the site of spinal cord injury, regenerative biomaterials can fill cavities, deliver curative drugs, and provide adsorption sites for transplanted or host cells. Some regenerative biomaterials can also inhibit apoptosis, inflammation and glial scar formation, or further promote neurogenesis, axonal growth and angiogenesis. This review summarized a variety of biomaterial scaffolds made of natural, synthetic, and combined materials applied to spinal cord injury repair. Although these biomaterial scaffolds have shown a certain therapeutic effect in spinal cord injury repair, there are still many problems to be resolved, such as product standards and material safety and effectiveness.展开更多
Plasticity changes of uninjured nerves can result in a novel neural circuit after spinal cord injury, which can restore sensory and motor functions to different degrees. Although processes of neural plasticity have be...Plasticity changes of uninjured nerves can result in a novel neural circuit after spinal cord injury, which can restore sensory and motor functions to different degrees. Although processes of neural plasticity have been studied, the mechanism and treatment to effectively improve neural plasticity changes remain controversial. The present study reviewed studies regarding plasticity of the central nervous system and methods for promoting plasticity to improve repair of injured central nerves. The results showed that synaptic reorganization, axonal sprouting, and neurogenesis are critical factors for neural circuit reconstruction. Directed functional exercise, neurotrophic factor and transplantation of nerve-derived and non-nerve-derived tissues and cells can effectively ameliorate functional disturbances caused by spinal cord injury and improve quality of life for patients.展开更多
Delivery of a peptide(APP96-110),derived from amyloid precursor protein(APP),has been shown to elicit neuroprotective effects following cerebral stroke and traumatic brain injury.In this study,the effect of APP96-110 ...Delivery of a peptide(APP96-110),derived from amyloid precursor protein(APP),has been shown to elicit neuroprotective effects following cerebral stroke and traumatic brain injury.In this study,the effect of APP96-110 or a mutant version of this peptide(mAPP96-110)was assessed following moderate(200 kdyn,(2 N))thoracic contusive spinal cord injury(SCI)in adult Nude rats.Animals received a single tail vein injection of APP96-110 or mAPP96-110 at 30 minutes post-SCI and were then assessed for functional improvements over the next 8 weeks.A cohort of animals also received transplants of either viable or non-viable human mesenchymal stromal cells(hMSCs)into the SC lesion site at one week post-injury to assess the effect of combining intravenous APP96-110 delivery with hMSC treatment.Rats were perfused 8 weeks post-SCI and longitudinal sections of spinal cord analyzed for a number of factors including hMSC viability,cyst size,axonal regrowth,glial reactivity and macrophage activation.Analysis of sensorimotor function revealed occasional significant differences between groups using Ladderwalk or Ratwalk tests,however there were no consistent improvements in functional outcome after any of the treatments.mAPP96-110 alone,and APP96-110 in combination with both viable and non-viable hMSCs significantly reduced cyst size compared to SCI alone.Combined treatments with donor hMSCs also significantly increased βIII tubulin^(+),glial fibrillary acidic protein(GFAP^(+))and laminin+expression,and decreased ED1^(+)expression in tissues.This preliminary study demonstrates that intravenous delivery of APP96-110 peptide has selective,modest neuroprotective effects following SCI,which may be enhanced when combined with hMSC transplantation.However,the effects are less pronounced and less consistent compared to the protective morphological and cognitive impact that this same peptide has on neuronal survival and behaviour after stroke and traumatic brain injury.Thus while the efficacy of a particular therapeutic approach in one CNS injury model may provide justification for its use in other neurotrauma models,similar outcomes may not necessarily occur and more targeted approaches suited to location and severity are required.All animal experiments were approved by The University of Western Australia Animal Ethics Committee(RA3/100/1460)on April 12,2016.展开更多
基金supported by the National Natural Science Foundation of China,No.81571213(to BW),No.81800583(to YYX)the 13~(th) Six Talent Peaks Project(C type)of Jiangsu Province of China(to BW)+1 种基金the Medical Science and Technique Development Foundation of Nanjing of China,No.QRX17006(to BW)the Medical Science and Innovation Platform of Nanjing of China,No.ZDX16005(to BW)
文摘Axonal junction defects and an inhibitory environment after spinal cord injury seriously hinder the regeneration of damaged tissues and neuronal functions. At the site of spinal cord injury, regenerative biomaterials can fill cavities, deliver curative drugs, and provide adsorption sites for transplanted or host cells. Some regenerative biomaterials can also inhibit apoptosis, inflammation and glial scar formation, or further promote neurogenesis, axonal growth and angiogenesis. This review summarized a variety of biomaterial scaffolds made of natural, synthetic, and combined materials applied to spinal cord injury repair. Although these biomaterial scaffolds have shown a certain therapeutic effect in spinal cord injury repair, there are still many problems to be resolved, such as product standards and material safety and effectiveness.
基金supported by the National Natural Science Foundation of China (Goat model of ischemic injury in corticospinal tract projection path and axonal guidance of MPA-1B migration in the spinal cord), No. 30972153the National Natural Science Foundation of China (Spinal cord ischemia/reperfusion injury and proteomics), No. 30872609
文摘Plasticity changes of uninjured nerves can result in a novel neural circuit after spinal cord injury, which can restore sensory and motor functions to different degrees. Although processes of neural plasticity have been studied, the mechanism and treatment to effectively improve neural plasticity changes remain controversial. The present study reviewed studies regarding plasticity of the central nervous system and methods for promoting plasticity to improve repair of injured central nerves. The results showed that synaptic reorganization, axonal sprouting, and neurogenesis are critical factors for neural circuit reconstruction. Directed functional exercise, neurotrophic factor and transplantation of nerve-derived and non-nerve-derived tissues and cells can effectively ameliorate functional disturbances caused by spinal cord injury and improve quality of life for patients.
基金the Neurotrauma Research Program of Western Australia.
文摘Delivery of a peptide(APP96-110),derived from amyloid precursor protein(APP),has been shown to elicit neuroprotective effects following cerebral stroke and traumatic brain injury.In this study,the effect of APP96-110 or a mutant version of this peptide(mAPP96-110)was assessed following moderate(200 kdyn,(2 N))thoracic contusive spinal cord injury(SCI)in adult Nude rats.Animals received a single tail vein injection of APP96-110 or mAPP96-110 at 30 minutes post-SCI and were then assessed for functional improvements over the next 8 weeks.A cohort of animals also received transplants of either viable or non-viable human mesenchymal stromal cells(hMSCs)into the SC lesion site at one week post-injury to assess the effect of combining intravenous APP96-110 delivery with hMSC treatment.Rats were perfused 8 weeks post-SCI and longitudinal sections of spinal cord analyzed for a number of factors including hMSC viability,cyst size,axonal regrowth,glial reactivity and macrophage activation.Analysis of sensorimotor function revealed occasional significant differences between groups using Ladderwalk or Ratwalk tests,however there were no consistent improvements in functional outcome after any of the treatments.mAPP96-110 alone,and APP96-110 in combination with both viable and non-viable hMSCs significantly reduced cyst size compared to SCI alone.Combined treatments with donor hMSCs also significantly increased βIII tubulin^(+),glial fibrillary acidic protein(GFAP^(+))and laminin+expression,and decreased ED1^(+)expression in tissues.This preliminary study demonstrates that intravenous delivery of APP96-110 peptide has selective,modest neuroprotective effects following SCI,which may be enhanced when combined with hMSC transplantation.However,the effects are less pronounced and less consistent compared to the protective morphological and cognitive impact that this same peptide has on neuronal survival and behaviour after stroke and traumatic brain injury.Thus while the efficacy of a particular therapeutic approach in one CNS injury model may provide justification for its use in other neurotrauma models,similar outcomes may not necessarily occur and more targeted approaches suited to location and severity are required.All animal experiments were approved by The University of Western Australia Animal Ethics Committee(RA3/100/1460)on April 12,2016.
