This study established a dog model of acute multiple cauda equina constriction by experimental constriction injury （48 hours） of the lumbosacral central processes in dorsal root ganglia neurons. The repair effect of...This study established a dog model of acute multiple cauda equina constriction by experimental constriction injury （48 hours） of the lumbosacral central processes in dorsal root ganglia neurons. The repair effect of intrathecal injection of brain-derived neurotrophic factor with 15 mg encapsulated biodegradable poly（lactide-co-glycolide） nanoparticles on this injury was then analyzed. Dorsal root ganglion cells （LT） of all experimental dogs were analyzed using hematoxylin-eosin staining and immunohistochemistry at 1,2 and 4 weeks following model induction. Intrathecal injection of brain-derived neurotrophic factor can relieve degeneration and inflammation, and elevate the expression of brain-derived neurotrophic factor in sensory neurons of compressed dorsal root ganglion Simultaneously, intrathecal injection of brain-derived neurotrophic factor obviously improved neurological function in the dog model of acute multiple cauda equina constriction. Results verified that sustained intraspinal delivery of brain-derived neurotrophic factor encapsulated in biodegradable nanoparticles promoted the repair of histomorphology and function of neurons within the dorsal root ganglia in dogs with acute and severe cauda equina syndrome.展开更多
1.Background.Polymethyl methacrylate(PMMA)bone cement has been widely used in orthopedic clinics for over 70 years.In 1952 and 1953,Kiaer and Haboush reported their work on the use of PMMA cement to achieve bone adher...1.Background.Polymethyl methacrylate(PMMA)bone cement has been widely used in orthopedic clinics for over 70 years.In 1952 and 1953,Kiaer and Haboush reported their work on the use of PMMA cement to achieve bone adherence to prostheses in femoral head replacement[1,2],.In 1987,Galibert et al.first reported the use of PMMA cement in spinal surgery for vertebroplasty(PVP)to treat vertebral hemangiomas[3].By 2002,approximately 38,000 vertebroplasties and 16,000 kyphoplasties were performed in the United States[4].展开更多
Imbalance of oxidative and inflammatory regulation is themain contributor to neurofunctional deterioration and failure of rebuilding spared neural networks after spinal cord injury(SCI).As an emerging biosafe strategy...Imbalance of oxidative and inflammatory regulation is themain contributor to neurofunctional deterioration and failure of rebuilding spared neural networks after spinal cord injury(SCI).As an emerging biosafe strategy for protecting against oxidative and inflammatory damage,hydrogen(H_(2))therapy is a promising approach for improving the microenvironment to allow neural regeneration.However,achieving release of H_(2) at sufficient concentrations specifically into the injured area is critical for the therapeutic effect of H_(2).Thus,we assembled SiO_(2)@mSiO_(2) mesoporous silica nanoparticles and loaded them with ammonia borane(AB),which has abundant capacity and allows controllable release of H_(2) in an acid-dependent manner.The release of H_(2) from AB/SiO_(2)@mSiO_(2) was satisfactory at pH 6.6,which is approximately equal to the microenvironmental acidity after SCI.After AB/SiO_(2)@mSiO_(2) were intrathecally administered to ratmodels of SCI,continuous release of H_(2) fromthese nanoparticles synergistically enhanced neurofunctional recovery,reduced fibrotic scar formation and promoted neural regeneration by suppressing oxidative stress reaction.Furthermore,in the subacute phase of SCI,microglia were markedly polarized toward the M2 phenotype by H_(2) via inhibition of TLR9 expression in astrocytes.In conclusion,H_(2) delivery through AB/SiO_(2)@mSiO_(2) has the potential to efficiently treat SCI through comprehensivemodulation of the oxidative and inflammatory imbalance in themicroenvironment.展开更多
基金supported by grants from the Medical Scientific Fund and Intensive Research of Nanjing Military Area Command of Chinese PLA, No.Nan2007-13 and Nan 08Z003the Medical Scientific Fund and Research of Chinese PLA during the 12th Five-Year Plan Period,No.CWS11J260
文摘This study established a dog model of acute multiple cauda equina constriction by experimental constriction injury （48 hours） of the lumbosacral central processes in dorsal root ganglia neurons. The repair effect of intrathecal injection of brain-derived neurotrophic factor with 15 mg encapsulated biodegradable poly（lactide-co-glycolide） nanoparticles on this injury was then analyzed. Dorsal root ganglion cells （LT） of all experimental dogs were analyzed using hematoxylin-eosin staining and immunohistochemistry at 1,2 and 4 weeks following model induction. Intrathecal injection of brain-derived neurotrophic factor can relieve degeneration and inflammation, and elevate the expression of brain-derived neurotrophic factor in sensory neurons of compressed dorsal root ganglion Simultaneously, intrathecal injection of brain-derived neurotrophic factor obviously improved neurological function in the dog model of acute multiple cauda equina constriction. Results verified that sustained intraspinal delivery of brain-derived neurotrophic factor encapsulated in biodegradable nanoparticles promoted the repair of histomorphology and function of neurons within the dorsal root ganglia in dogs with acute and severe cauda equina syndrome.
基金supported by the National Natural Science Foundation of China(No.82272165)the Shanghai Committee of Science and Technology(No.20ZR1451800)+1 种基金the Municipal Health Commission Fundation of Shanghai(No.202040141)the Outstanding Youth Foundation Project of Tongren(No.2020SHTRYC02)。
文摘1.Background.Polymethyl methacrylate(PMMA)bone cement has been widely used in orthopedic clinics for over 70 years.In 1952 and 1953,Kiaer and Haboush reported their work on the use of PMMA cement to achieve bone adherence to prostheses in femoral head replacement[1,2],.In 1987,Galibert et al.first reported the use of PMMA cement in spinal surgery for vertebroplasty(PVP)to treat vertebral hemangiomas[3].By 2002,approximately 38,000 vertebroplasties and 16,000 kyphoplasties were performed in the United States[4].
基金supported by the National Natural Science Foundation of China(81772445)the Natural Science Foundation of Shanghai,China(20ZR1469800)+1 种基金the Shanghai Sailing Program(19YF1448400)the National Science Foundation for Post-doctoral Scientists of China(2020M683733).
文摘Imbalance of oxidative and inflammatory regulation is themain contributor to neurofunctional deterioration and failure of rebuilding spared neural networks after spinal cord injury(SCI).As an emerging biosafe strategy for protecting against oxidative and inflammatory damage,hydrogen(H_(2))therapy is a promising approach for improving the microenvironment to allow neural regeneration.However,achieving release of H_(2) at sufficient concentrations specifically into the injured area is critical for the therapeutic effect of H_(2).Thus,we assembled SiO_(2)@mSiO_(2) mesoporous silica nanoparticles and loaded them with ammonia borane(AB),which has abundant capacity and allows controllable release of H_(2) in an acid-dependent manner.The release of H_(2) from AB/SiO_(2)@mSiO_(2) was satisfactory at pH 6.6,which is approximately equal to the microenvironmental acidity after SCI.After AB/SiO_(2)@mSiO_(2) were intrathecally administered to ratmodels of SCI,continuous release of H_(2) fromthese nanoparticles synergistically enhanced neurofunctional recovery,reduced fibrotic scar formation and promoted neural regeneration by suppressing oxidative stress reaction.Furthermore,in the subacute phase of SCI,microglia were markedly polarized toward the M2 phenotype by H_(2) via inhibition of TLR9 expression in astrocytes.In conclusion,H_(2) delivery through AB/SiO_(2)@mSiO_(2) has the potential to efficiently treat SCI through comprehensivemodulation of the oxidative and inflammatory imbalance in themicroenvironment.
