The need for the continuous research of new tools for improving motor function recovery after nerve injury is justified by the still often unsatisfactory clinical outcome in these patients. It has been previously show...The need for the continuous research of new tools for improving motor function recovery after nerve injury is justified by the still often unsatisfactory clinical outcome in these patients. It has been previously shown that the combined use of two reconstructive techniques, namely end-to-side neurorrhaphy and direct muscle neurotization in the rat hindlimb model, can lead to good results in terms of skeletal muscle reinnervation. Here we show that, in the rat forelimb model, the combined use of direct muscle neurotization with either end-to-end or end-to-side neurorrhaphy to reinnervate the denervated flexor digitorum muscles, leads to muscle atrophy prevention over a long postoperative time lapse （10 months）. By contrast, very little motor recovery （in case of end-to-end neurorrhaphy） and almost no motor recovery （in case of end-to-side neurorrhaphy） were observed in the grasping activity controlled by flexor digitorum muscles. It can thus be concluded that, at least in the rat, direct muscle neurotization after both end-to-end and end-to-side neurorrhaphy represents a good strategy for preventing denervation-related muscle atrophy but not for regaining the lost motor function.展开更多
Most researchers believe that neurogenesis in mature mammals is restricted only to the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricle in the central nervous system. In the p...Most researchers believe that neurogenesis in mature mammals is restricted only to the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricle in the central nervous system. In the peripheral nervous system, neurogenesis is thought to be active only during prenatal development, with the exception of the olfactory neuroepithelium. However, sensory ganglia in the adult peripheral nervous system have been reported to contain precursor cells that can proliferate in vitro and be induced to differentiate into neurons. The occurrence of insult-induced neurogenesis, which has been reported by several investigators in the brain, is limited to a few recent reports for the peripheral nervous system. These reports suggest that damage to the adult nervous system induces mechanisms similar to those that control the generation of new neurons during prenatal development. Understanding conditions under which neurogenesis can be induced in physiologically non-neurogenic regions in adults is one of the major challenges for developing therapeutic strategies to repair neurological damage. However, the induced neurogenesis in the peripheral nervous system is still largely unexplored. This review presents the history of research on adult neurogenesis in the peripheral nervous system, which dates back more than 100 years and reveals the evidence on the under estimated potential for generation of new neurons in the adult peripheral nervous system.展开更多
AIM: To study the therapeutic effect of three tubeguides with electrical conductivity associated to mesenchymal stem cells(MSCs) on neuro-muscular regeneration after neurotmesis.METHODS: Rats with 10-mm gap nerve inju...AIM: To study the therapeutic effect of three tubeguides with electrical conductivity associated to mesenchymal stem cells(MSCs) on neuro-muscular regeneration after neurotmesis.METHODS: Rats with 10-mm gap nerve injury were tested using polyvinyl alcohol(PVA), PVA-carbon nanotubes(CNTs) and MSCs, and PVA-polypyrrole(PPy). The regenerated nerves and tibialis anterior muscles were processed for stereological studies after 20 wk. The functional recovery was assessed serially for gait biomechanical analysis, by extensor postural thrust, sciatic functional index and static sciatic functionalindex(SSI), and by withdrawal reflex latency(WRL). In vitro studies included cytocompatibility, flow cytometry, reverse transcriptase polymerase chain reaction and karyotype analysis of the MSCs. Histopathology of lung, liver, kidneys, and regional lymph nodes ensured the biomaterials biocompatibility. RESULTS: SSI remained negative throughout and independently from treatment. Differences between treted groups in the severity of changes in WRL existed, showing a faster regeneration for PVA-CNTs-MSCs(P < 0.05). At toe-off, less acute ankle joint angles were seen for PVA-CNTs-MSCs group(P = 0.051) suggesting improved ankle muscles function during the push off phase of the gait cycle. In PVA-PPy and PVA-CNTs groups, there was a 25% and 42% increase of average fiber area and a 13% and 21% increase of the "minimal Feret's diameter" respectively. Stereological analysis disclosed a significantly(P < 0.05) increased myelin thickness(M), ratio myelin thickness/axon diameter(M/d) and ratio axon diameter/fiber diameter(d/D; g-ratio) in PVA-CNT-MSCs group(P < 0.05). CONCLUSION: Results revealed that treatment with MSCs and PVA-CNTs tube-guides induced better nerve fiber regeneration. Functional and kinematics analysis revealed positive synergistic effects brought by MSCs and PVA-CNTs. The PVA-CNTs and PVA-PPy are promising scaffolds with electric conductive properties, bio- and cytocompatible that might prevent the secondary neurogenic muscular atrophy by improving the reestablishment of the neuro-muscular junction.展开更多
More than twenty years ago, when I first started working on plasticity and regeneration in the peripheral nervous system, I had the feeling of being part of a little, though lively, scientific community that was rarth...More than twenty years ago, when I first started working on plasticity and regeneration in the peripheral nervous system, I had the feeling of being part of a little, though lively, scientific community that was rarther isolated in the world of neuroscience which appeared to me as almost only focused on central nervous system. Since then, things have progressively changed very much and, today, interest in the regeneration in the peripheral nervous system, and especially in its main component. Le. the peripheral nerves （Geuna S, Raimondo S, Ronchi G, et al. Histology of the peripheral nerve and changes occurring during nerve regeneration. Int Rev Neurobiol. 2009;87：27-46.）, is sprading tremendouslty among both basic and clinical neuroscientists.展开更多
基金supported by San Paolo Bank Foundationthe Italian Ministry of University
文摘The need for the continuous research of new tools for improving motor function recovery after nerve injury is justified by the still often unsatisfactory clinical outcome in these patients. It has been previously shown that the combined use of two reconstructive techniques, namely end-to-side neurorrhaphy and direct muscle neurotization in the rat hindlimb model, can lead to good results in terms of skeletal muscle reinnervation. Here we show that, in the rat forelimb model, the combined use of direct muscle neurotization with either end-to-end or end-to-side neurorrhaphy to reinnervate the denervated flexor digitorum muscles, leads to muscle atrophy prevention over a long postoperative time lapse （10 months）. By contrast, very little motor recovery （in case of end-to-end neurorrhaphy） and almost no motor recovery （in case of end-to-side neurorrhaphy） were observed in the grasping activity controlled by flexor digitorum muscles. It can thus be concluded that, at least in the rat, direct muscle neurotization after both end-to-end and end-to-side neurorrhaphy represents a good strategy for preventing denervation-related muscle atrophy but not for regaining the lost motor function.
文摘Most researchers believe that neurogenesis in mature mammals is restricted only to the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricle in the central nervous system. In the peripheral nervous system, neurogenesis is thought to be active only during prenatal development, with the exception of the olfactory neuroepithelium. However, sensory ganglia in the adult peripheral nervous system have been reported to contain precursor cells that can proliferate in vitro and be induced to differentiate into neurons. The occurrence of insult-induced neurogenesis, which has been reported by several investigators in the brain, is limited to a few recent reports for the peripheral nervous system. These reports suggest that damage to the adult nervous system induces mechanisms similar to those that control the generation of new neurons during prenatal development. Understanding conditions under which neurogenesis can be induced in physiologically non-neurogenic regions in adults is one of the major challenges for developing therapeutic strategies to repair neurological damage. However, the induced neurogenesis in the peripheral nervous system is still largely unexplored. This review presents the history of research on adult neurogenesis in the peripheral nervous system, which dates back more than 100 years and reveals the evidence on the under estimated potential for generation of new neurons in the adult peripheral nervous system.
基金Supported by System of Incentives for Research and Technological development of QREN in the scope of project n°38853/2013-DEXGELERATION:"Solucoes avancadas de regeneracao ossea com base em hidrogeis de dextrin"the European Community FEDER fund through ON2-O Novo Norte-North Portugal Regional Operational Program 2007-2013+4 种基金Project n°34128-BEPIM II:"Microdispositivos biomédicos com capacidade osteointegrativa porμPIM"funded by Ad Ithe program COMPETE-Programa Operacional Factores de Competitividade,projects Pest-OE/AGR/UI0211/2011PTDC/CVT/103081/2008CDRsp’s Strategic Project-UI-4044-2011-2012(Pest-OE/EME/UI4044/2011)funding from FCT
文摘AIM: To study the therapeutic effect of three tubeguides with electrical conductivity associated to mesenchymal stem cells(MSCs) on neuro-muscular regeneration after neurotmesis.METHODS: Rats with 10-mm gap nerve injury were tested using polyvinyl alcohol(PVA), PVA-carbon nanotubes(CNTs) and MSCs, and PVA-polypyrrole(PPy). The regenerated nerves and tibialis anterior muscles were processed for stereological studies after 20 wk. The functional recovery was assessed serially for gait biomechanical analysis, by extensor postural thrust, sciatic functional index and static sciatic functionalindex(SSI), and by withdrawal reflex latency(WRL). In vitro studies included cytocompatibility, flow cytometry, reverse transcriptase polymerase chain reaction and karyotype analysis of the MSCs. Histopathology of lung, liver, kidneys, and regional lymph nodes ensured the biomaterials biocompatibility. RESULTS: SSI remained negative throughout and independently from treatment. Differences between treted groups in the severity of changes in WRL existed, showing a faster regeneration for PVA-CNTs-MSCs(P < 0.05). At toe-off, less acute ankle joint angles were seen for PVA-CNTs-MSCs group(P = 0.051) suggesting improved ankle muscles function during the push off phase of the gait cycle. In PVA-PPy and PVA-CNTs groups, there was a 25% and 42% increase of average fiber area and a 13% and 21% increase of the "minimal Feret's diameter" respectively. Stereological analysis disclosed a significantly(P < 0.05) increased myelin thickness(M), ratio myelin thickness/axon diameter(M/d) and ratio axon diameter/fiber diameter(d/D; g-ratio) in PVA-CNT-MSCs group(P < 0.05). CONCLUSION: Results revealed that treatment with MSCs and PVA-CNTs tube-guides induced better nerve fiber regeneration. Functional and kinematics analysis revealed positive synergistic effects brought by MSCs and PVA-CNTs. The PVA-CNTs and PVA-PPy are promising scaffolds with electric conductive properties, bio- and cytocompatible that might prevent the secondary neurogenic muscular atrophy by improving the reestablishment of the neuro-muscular junction.
文摘More than twenty years ago, when I first started working on plasticity and regeneration in the peripheral nervous system, I had the feeling of being part of a little, though lively, scientific community that was rarther isolated in the world of neuroscience which appeared to me as almost only focused on central nervous system. Since then, things have progressively changed very much and, today, interest in the regeneration in the peripheral nervous system, and especially in its main component. Le. the peripheral nerves （Geuna S, Raimondo S, Ronchi G, et al. Histology of the peripheral nerve and changes occurring during nerve regeneration. Int Rev Neurobiol. 2009;87：27-46.）, is sprading tremendouslty among both basic and clinical neuroscientists.
