Following successful establishment of a rat model of spinal cord hemisection injury by resecting right spinal cord tissues, bone marrow stem cells were transplanted into the spinal cord lesions via the caudal vein whi...Following successful establishment of a rat model of spinal cord hemisection injury by resecting right spinal cord tissues, bone marrow stem cells were transplanted into the spinal cord lesions via the caudal vein while maintaining rectal temperature at 34 ± 0.5°C for 6 hours （mild hypothermia）. Hematoxylin-eosin staining showed that astrocytes gathered around the injury site and formed scars at 4 weeks post-transplantation. Compared with rats transplanted with bone marrow stem cells under normal temperature, rats transplanted with bone marrow stem cells under hypothermia showed increased numbers of proliferating cells （bromodeoxyuridine-positive cells）, better recovery of somatosensory-evoked and motor-evoked potentials, greater Basso, Beattie, and Bresnahan locomotor rating scores, and an increased degree of angle in the incline plate test. These findings suggested that hypothermia combined with bone marrow mesenchymal stem cells transplantation effectively promoted electrical conduction and nerve functional repair in a rat model of spinal cord hemisection injury.展开更多
Biomaterial bridging provides physical substrates to guide axonal growth across the lesion.To achieve efficient directional guidance,combinatory strategies using permissive matrix,cells and trophic factors are necessa...Biomaterial bridging provides physical substrates to guide axonal growth across the lesion.To achieve efficient directional guidance,combinatory strategies using permissive matrix,cells and trophic factors are necessary.In the present study,we evaluated permissive effect of poly(acrylonitrile-co-vinyl chloride)guidance channels filled by different densities of laminin-precoated unidirectional polypropylene filaments combined with Schwann cells,and glial cell line-derived neurotrophic factor for axonal regeneration through a T10 hemisected spinal cord gap in adult rats.We found that channels with filaments significantly reduced the lesion cavity,astrocytic gliosis,and inflammatory responses at the graft-host boundaries.The laminin coated low density filament provided the most favorable directional guidance for axonal regeneration which was enhanced by co-grafting of Schwann cells and glial cell line-derived neurotrophic factor.These results demonstrate that the combinatorial strategy of filament-filled guiding scaffold,adhesive molecular laminin,Schwann cells,and glial cell line-derived neurotrophic factor,provides optimal topographical cues in stimulating directional axonal regeneration following spinal cord injury.This study was approved by Indiana University Institutional Animal Care and Use Committees(IACUC#:11011)on October 29,2015.展开更多
This study established the following groups of rats： a normal group, a sham surgery group, a spinal cord injury model group, a low-frequency electroacupuncture group, a high-frequency electroacupuncture group and a s...This study established the following groups of rats： a normal group, a sham surgery group, a spinal cord injury model group, a low-frequency electroacupuncture group, a high-frequency electroacupuncture group and a semen coicis group. In all but the normal and sham surgery groups the left half of Tlo was transected. Four hours after model induction, 5-Hz and 100-Hz electroacupuncture were used to stimulate the acupoints I-luantiao （GB 30）, Zusan/i （ST 36）, Zhiyan9 （DU 9） and Xuanshu （DU 5）, or crude extract from semen coicis was intraperitoneally injected, for 8 consecutive weeks. The results indicated that electroacupuncture stimulation and intraperitoneal injection of semen coicis improved the morphology of spinal cord tissue, promoted the recovery of motion-evoked potentials, suppressed glial fibrillary acidic protein expression, and ameliorated motor function in rats with hemisection spinal cord injury. The effects of high-frequency （100 Hz） electroacupuncture ancl semen coicis were significant.展开更多
We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staini...We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 （Schwann cell marker） and glial fibrillary acidic protein （glial cell marker） at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvi- ronment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury.展开更多
The initial mechanical damage of a spinal cord injury(SCI)triggers a progressive secondary injury cascade,which is a complicated process integrating multiple systems and cells.It is crucial to explore the molecular an...The initial mechanical damage of a spinal cord injury(SCI)triggers a progressive secondary injury cascade,which is a complicated process integrating multiple systems and cells.It is crucial to explore the molecular and biological process alterations that occur after SCI for therapy development.The differences between the rostral and caudal regions around an SCI lesion have received little attention.Here,we analyzed the differentially expressed genes between rostral and caudal sites after injury to determine the biological processes in these two segments after SCI.We identified a set of differentially expressed genes,including Col3a1,Col1a1,Dcn,Fn1,Kcnk3,and Nrg1,between rostral and caudal regions at different time points following SCI.Functional enrichment analysis indicated that these genes were involved in response to mechanical stimulus,blood vessel development,and brain development.We then chose Col3a1,Col1a1,Dcn,Fn1,Kcnk3,and Nrg1 for quantitative real-time PCR and Fn1 for immunostaining validation.Our results indicate alterations in different biological events enriched in the rostral and caudal lesion areas,providing new insights into the pathology of SCI.展开更多
目的建立一种新型大鼠脊髓半切模型,为临床脊髓空洞损伤研究提供适宜的动物模型。方法 25只SD大鼠随机分为脊髓楔型块状半切组(A组,n=10)、假手术组(B组,n=10)和正常对照组(C组,n=5)。术后采用BBB运动功能评分、斜板试验、HE染色和核磁...目的建立一种新型大鼠脊髓半切模型,为临床脊髓空洞损伤研究提供适宜的动物模型。方法 25只SD大鼠随机分为脊髓楔型块状半切组(A组,n=10)、假手术组(B组,n=10)和正常对照组(C组,n=5)。术后采用BBB运动功能评分、斜板试验、HE染色和核磁共振(MRI)检测综合评价脊髓半切模型的稳定性。结果术后A组大鼠伤侧后肢BBB运动功能评分及斜板维持最大角度值显著低于B组和C组(P<0.05),而这些指标在B组和C组之间没有明显差异;术后28 d HE和MRI检测显示脊髓损伤区(A组)灰质和白质发生明显的形态学改变。结论通过该方法建立的脊髓半切模型稳定、可靠,适于脊髓空洞性损伤的研究。展开更多
基金sponsored by the Science and Technology Foundation of Tianjin Health Bureau, No. 2010ky04Application Basic and Front Technology Projects of Tianjin(Science and Technology Foundation of Tianjin)No.12JCYBJC18000
文摘Following successful establishment of a rat model of spinal cord hemisection injury by resecting right spinal cord tissues, bone marrow stem cells were transplanted into the spinal cord lesions via the caudal vein while maintaining rectal temperature at 34 ± 0.5°C for 6 hours （mild hypothermia）. Hematoxylin-eosin staining showed that astrocytes gathered around the injury site and formed scars at 4 weeks post-transplantation. Compared with rats transplanted with bone marrow stem cells under normal temperature, rats transplanted with bone marrow stem cells under hypothermia showed increased numbers of proliferating cells （bromodeoxyuridine-positive cells）, better recovery of somatosensory-evoked and motor-evoked potentials, greater Basso, Beattie, and Bresnahan locomotor rating scores, and an increased degree of angle in the incline plate test. These findings suggested that hypothermia combined with bone marrow mesenchymal stem cells transplantation effectively promoted electrical conduction and nerve functional repair in a rat model of spinal cord hemisection injury.
基金Research in the Xu laboratory is supported by NIH 1R01100531,1R01 NS103481Merit Review Award I01 BX002356,I01 BX003705,I01 RX002687 from the U.S.Department of Veterans AffairsMari Hulman George Endowment Funds.
文摘Biomaterial bridging provides physical substrates to guide axonal growth across the lesion.To achieve efficient directional guidance,combinatory strategies using permissive matrix,cells and trophic factors are necessary.In the present study,we evaluated permissive effect of poly(acrylonitrile-co-vinyl chloride)guidance channels filled by different densities of laminin-precoated unidirectional polypropylene filaments combined with Schwann cells,and glial cell line-derived neurotrophic factor for axonal regeneration through a T10 hemisected spinal cord gap in adult rats.We found that channels with filaments significantly reduced the lesion cavity,astrocytic gliosis,and inflammatory responses at the graft-host boundaries.The laminin coated low density filament provided the most favorable directional guidance for axonal regeneration which was enhanced by co-grafting of Schwann cells and glial cell line-derived neurotrophic factor.These results demonstrate that the combinatorial strategy of filament-filled guiding scaffold,adhesive molecular laminin,Schwann cells,and glial cell line-derived neurotrophic factor,provides optimal topographical cues in stimulating directional axonal regeneration following spinal cord injury.This study was approved by Indiana University Institutional Animal Care and Use Committees(IACUC#:11011)on October 29,2015.
基金the High-funded Projects of Japan Science and Technology Ministry,No. 343the National Natural Science Foundation of China,No. 30772838
文摘This study established the following groups of rats： a normal group, a sham surgery group, a spinal cord injury model group, a low-frequency electroacupuncture group, a high-frequency electroacupuncture group and a semen coicis group. In all but the normal and sham surgery groups the left half of Tlo was transected. Four hours after model induction, 5-Hz and 100-Hz electroacupuncture were used to stimulate the acupoints I-luantiao （GB 30）, Zusan/i （ST 36）, Zhiyan9 （DU 9） and Xuanshu （DU 5）, or crude extract from semen coicis was intraperitoneally injected, for 8 consecutive weeks. The results indicated that electroacupuncture stimulation and intraperitoneal injection of semen coicis improved the morphology of spinal cord tissue, promoted the recovery of motion-evoked potentials, suppressed glial fibrillary acidic protein expression, and ameliorated motor function in rats with hemisection spinal cord injury. The effects of high-frequency （100 Hz） electroacupuncture ancl semen coicis were significant.
基金supported by grants from the National Program on Key Basic Research Project of China(973 Program),No.2014CB542201Program for Innovative Research Team in University of Ministry of Education of China,No.IRT1201+2 种基金the National Natural Science Foundation of China,No.31271284,31171150,81171146,30971526,31100860,31040043Program for New Century Excellent Talents in University of Ministry of Education of China,No.BMU20110270the Natural Science Foundation of Beijing of China,No.7142164
文摘We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 （Schwann cell marker） and glial fibrillary acidic protein （glial cell marker） at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvi- ronment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury.
基金supported by Postgraduate Research&Practice Innovation Program of Jiangsu Province,No.KYCX-2065(to XMC).
文摘The initial mechanical damage of a spinal cord injury(SCI)triggers a progressive secondary injury cascade,which is a complicated process integrating multiple systems and cells.It is crucial to explore the molecular and biological process alterations that occur after SCI for therapy development.The differences between the rostral and caudal regions around an SCI lesion have received little attention.Here,we analyzed the differentially expressed genes between rostral and caudal sites after injury to determine the biological processes in these two segments after SCI.We identified a set of differentially expressed genes,including Col3a1,Col1a1,Dcn,Fn1,Kcnk3,and Nrg1,between rostral and caudal regions at different time points following SCI.Functional enrichment analysis indicated that these genes were involved in response to mechanical stimulus,blood vessel development,and brain development.We then chose Col3a1,Col1a1,Dcn,Fn1,Kcnk3,and Nrg1 for quantitative real-time PCR and Fn1 for immunostaining validation.Our results indicate alterations in different biological events enriched in the rostral and caudal lesion areas,providing new insights into the pathology of SCI.
文摘目的建立一种新型大鼠脊髓半切模型,为临床脊髓空洞损伤研究提供适宜的动物模型。方法 25只SD大鼠随机分为脊髓楔型块状半切组(A组,n=10)、假手术组(B组,n=10)和正常对照组(C组,n=5)。术后采用BBB运动功能评分、斜板试验、HE染色和核磁共振(MRI)检测综合评价脊髓半切模型的稳定性。结果术后A组大鼠伤侧后肢BBB运动功能评分及斜板维持最大角度值显著低于B组和C组(P<0.05),而这些指标在B组和C组之间没有明显差异;术后28 d HE和MRI检测显示脊髓损伤区(A组)灰质和白质发生明显的形态学改变。结论通过该方法建立的脊髓半切模型稳定、可靠,适于脊髓空洞性损伤的研究。
