Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal contr...Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal control of neurons. This drawback increases side effects due to non-specific targeting. Optogenetics is a technology that allows precise spatial and temporal control of cells. Therefore, this technique has high potential as a therapeutic strategy for neurological diseases. Even though the application of optogenetics in understanding brain functional organization and complex behaviour states have been elaborated, reviews of its therapeutic potential especially in neurodegeneration and regeneration are still limited. This short review presents representative work in optogenetics in disease models such as spinal cord injury, multiple sclerosis, epilepsy, Alzheimer＇s disease and Parkinson＇s disease. It is aimed to provide a broader perspective on optogenetic therapeutic potential in neurodegeneration and neural regeneration.展开更多
This paper introduces in details a kind of silicon-based microelectrode array. MEMS (micro-electromechanical system) technology is used in the fabrication of the microelectrode array, which is designed to perform sign...This paper introduces in details a kind of silicon-based microelectrode array. MEMS (micro-electromechanical system) technology is used in the fabrication of the microelectrode array, which is designed to perform signal recording and electrical stimulation for nerves in neural engineering. A simple fabrication process is developed. An improved model of microelectrodes is brought forward and successfully validated by the excellent match between circuit simulations and electrical measurements, including both magnitude and phase of microelectrode impedance. Compared with the simple one that is usually used, the improved model is believed to be an advance and more accurate. This modeling helps to improve the design of microelectrodes and understand the behavior of interface between electrode and cell. Furthermore, the microelectrode is proved to be a feasible tool for researches in neural engineering by successfully recording neural activities of sciatic nerve of a bullfrog.展开更多
The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of ef...The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of effective and safe therapeutic options for such patients.Despite the high prevalence of stroke and spinal cord injury in the general population,these conditions remain incurable and place a heavy burden on patients’families and on society more broadly.Neuroregeneration and neural engineering are diverse biomedical fields that attempt reparative treatments,utilizing stem cells-based strategies,biologically active molecules,nanotechnology,exosomes and highly tunable biodegradable systems(e.g.,certain hydrogels).Although there are studies demonstrating promising preclinical results,safe clinical translation has not yet been accomplished.A key gap in clinical translation is the absence of an ideal animal or ex vivo model that can perfectly simulate the human microenvironment,and also correspond to all the complex pathophysiological and neuroanatomical factors that affect functional outcomes in humans after central nervous system injury.Such an ideal model does not currently exist,but it seems that the nonhuman primate model is uniquely qualified for this role,given its close resemblance to humans.This review considers some regenerative therapies for central nervous system repair that hold promise for future clinical translation.In addition,it attempts to uncover some of the main reasons why clinical translation might fail without the implementation of nonhuman primate models in the research pipeline.展开更多
BACKGROUND：Previous tissue-engineered nerve studies have focused on artificial nerve and nerve cell cultures.The effects of regeneration chambers with autologous nerve bridging for the repair of nerve defects remain ...BACKGROUND：Previous tissue-engineered nerve studies have focused on artificial nerve and nerve cell cultures.The effects of regeneration chambers with autologous nerve bridging for the repair of nerve defects remain unclear.OBJECTIVE：To explore the feasibility and advantages of chitosan tube bridging autologous nerve segments for repairing 12-mm sciatic nerve defects in rats.DESIGN,TIME AND SETTING：A randomized,controlled,animal study using nerve tissue engineering was performed at the Animal Laboratory and Laboratory of Histology and Embryology,Liaoning Medical University from June 2008 to March 2009.MATERIALS：Chitosan powder was purchased from Jinan Haidebei Marine Bioengineering,China.METHODS：A sciatic nerve segment of approximately 8 mm was excised from the posterior margin of the piriformis muscle of Sprague Dawley rats.The two nerve ends shrank to form a 12-mm defect,and the nerve defect was repaired using a chitosan tube bridging autologous nerve segment （bridge group）,a chitosan tube-encapsulated autologous nerve segment （encapsulation group）,and a chitosan tube alone （chitosan tube alone group）,respectively.MAIN OUTCOME MEASURES：Histological and ultrastructural changes of the injured sciatic nerve;number of regenerated myelinated nerve fibers; nerve conduction velocity; leg muscle atrophy; and sciatic nerve functional index.RESULTS：At 4 months after implantation,the chitosan tube was absorbed.The tube was thin,but maintained the original shape,and vascular proliferation was observed around the tube.In the bridge group,regenerative myelinated nerve fibers were thick and orderly,with a thick myelin sheath and intact axonal structure.The number of myelinated nerve fibers and nerve conduction velocity were significantly greater compared with the other groups （P〈 0.01）.Moreover,nerve and muscle function was significantly improved following chitosan tube bridging autologous nerve segment treatment compared with the other groups （P〈 0.05 or P 〈 0.01）.CONCLUSION：Chitosan展开更多
Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following ner- vous system injury...Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following ner- vous system injury or neurodegenerative disease. Disconnection of axon pathways - the long-distance fibers connecting specialized regions of the central nervous system or relaying peripheral signals - is a common feature of many neurological disorders and injury. However, functional axonal regenera- tion rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engi- neered ＂living scaffolds＂, which are preformed three-dimensional constructs consisting of living neural cells in a defined, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration - mimicking key developmental mechanisms- or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal dusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in predinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery.展开更多
检索PubMed、Web of Science、中国知网等数据库中有关喉返神经损伤(RLNI)在甲状腺手术中的研究。关键词包括喉返神经修复、注射喉成形术、Ⅰ型甲状腺成形术、杓状软骨内收术、神经组织工程技术等。总结和比较目前RLNI的常见治疗方法。...检索PubMed、Web of Science、中国知网等数据库中有关喉返神经损伤(RLNI)在甲状腺手术中的研究。关键词包括喉返神经修复、注射喉成形术、Ⅰ型甲状腺成形术、杓状软骨内收术、神经组织工程技术等。总结和比较目前RLNI的常见治疗方法。结果显示,喉返神经直接缝合是目前修复的首选术式,颈袢-喉返神经吻合术最常用于临床,其他修复方式各有其优、缺点。大多数治疗方法可在一定程度上获得不同的效果,但仍存在需进一步克服的缺点。此外神经组织工程技术及中医康复治疗值得进一步探索关注。展开更多
基金supported in part by NIH NS059622,NS073636,DOD CDMRP W81XWH-12-1-0562,Merit Review Award I01 BX002356 from the U.SDepartment of Veterans Affairs,Craig H Neilsen Foundation 296749+1 种基金Indiana Spinal Cord and Brain Injury Research Foundation(ISCBIRF)019919Mari Hulman George Endowment Funds
文摘Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal control of neurons. This drawback increases side effects due to non-specific targeting. Optogenetics is a technology that allows precise spatial and temporal control of cells. Therefore, this technique has high potential as a therapeutic strategy for neurological diseases. Even though the application of optogenetics in understanding brain functional organization and complex behaviour states have been elaborated, reviews of its therapeutic potential especially in neurodegeneration and regeneration are still limited. This short review presents representative work in optogenetics in disease models such as spinal cord injury, multiple sclerosis, epilepsy, Alzheimer＇s disease and Parkinson＇s disease. It is aimed to provide a broader perspective on optogenetic therapeutic potential in neurodegeneration and neural regeneration.
基金Supported by the Natural Science Foundation of Zhejiang Province of China (Grant No. Y106448)State Key Laboratories of Transducer Technology (Grant No. SKT0506)
文摘This paper introduces in details a kind of silicon-based microelectrode array. MEMS (micro-electromechanical system) technology is used in the fabrication of the microelectrode array, which is designed to perform signal recording and electrical stimulation for nerves in neural engineering. A simple fabrication process is developed. An improved model of microelectrodes is brought forward and successfully validated by the excellent match between circuit simulations and electrical measurements, including both magnitude and phase of microelectrode impedance. Compared with the simple one that is usually used, the improved model is believed to be an advance and more accurate. This modeling helps to improve the design of microelectrodes and understand the behavior of interface between electrode and cell. Furthermore, the microelectrode is proved to be a feasible tool for researches in neural engineering by successfully recording neural activities of sciatic nerve of a bullfrog.
基金supported by Onassis Foundation(to MT)the National Center for Complementary and Integrative Health(NCCIH),No.R21AT008865(to NM)National Institute of Aging(NIA)/National Institute of Mental Health(NIMH),No.R01AG042512(to NM)
文摘The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of effective and safe therapeutic options for such patients.Despite the high prevalence of stroke and spinal cord injury in the general population,these conditions remain incurable and place a heavy burden on patients’families and on society more broadly.Neuroregeneration and neural engineering are diverse biomedical fields that attempt reparative treatments,utilizing stem cells-based strategies,biologically active molecules,nanotechnology,exosomes and highly tunable biodegradable systems(e.g.,certain hydrogels).Although there are studies demonstrating promising preclinical results,safe clinical translation has not yet been accomplished.A key gap in clinical translation is the absence of an ideal animal or ex vivo model that can perfectly simulate the human microenvironment,and also correspond to all the complex pathophysiological and neuroanatomical factors that affect functional outcomes in humans after central nervous system injury.Such an ideal model does not currently exist,but it seems that the nonhuman primate model is uniquely qualified for this role,given its close resemblance to humans.This review considers some regenerative therapies for central nervous system repair that hold promise for future clinical translation.In addition,it attempts to uncover some of the main reasons why clinical translation might fail without the implementation of nonhuman primate models in the research pipeline.
文摘BACKGROUND：Previous tissue-engineered nerve studies have focused on artificial nerve and nerve cell cultures.The effects of regeneration chambers with autologous nerve bridging for the repair of nerve defects remain unclear.OBJECTIVE：To explore the feasibility and advantages of chitosan tube bridging autologous nerve segments for repairing 12-mm sciatic nerve defects in rats.DESIGN,TIME AND SETTING：A randomized,controlled,animal study using nerve tissue engineering was performed at the Animal Laboratory and Laboratory of Histology and Embryology,Liaoning Medical University from June 2008 to March 2009.MATERIALS：Chitosan powder was purchased from Jinan Haidebei Marine Bioengineering,China.METHODS：A sciatic nerve segment of approximately 8 mm was excised from the posterior margin of the piriformis muscle of Sprague Dawley rats.The two nerve ends shrank to form a 12-mm defect,and the nerve defect was repaired using a chitosan tube bridging autologous nerve segment （bridge group）,a chitosan tube-encapsulated autologous nerve segment （encapsulation group）,and a chitosan tube alone （chitosan tube alone group）,respectively.MAIN OUTCOME MEASURES：Histological and ultrastructural changes of the injured sciatic nerve;number of regenerated myelinated nerve fibers; nerve conduction velocity; leg muscle atrophy; and sciatic nerve functional index.RESULTS：At 4 months after implantation,the chitosan tube was absorbed.The tube was thin,but maintained the original shape,and vascular proliferation was observed around the tube.In the bridge group,regenerative myelinated nerve fibers were thick and orderly,with a thick myelin sheath and intact axonal structure.The number of myelinated nerve fibers and nerve conduction velocity were significantly greater compared with the other groups （P〈 0.01）.Moreover,nerve and muscle function was significantly improved following chitosan tube bridging autologous nerve segment treatment compared with the other groups （P〈 0.05 or P 〈 0.01）.CONCLUSION：Chitosan
基金support provided by the U.S.Army Medical Research and Materiel Command through the Joint Warfighter Medical Research Program(#W81XWH-13-13207004)Axonia Medical,Inc.+3 种基金Department of Veterans Affairs(RR&D Merit Review#B1097-I)National Institutes of Health(NINDS T32-NS043126)Penn Medicine Neuroscience Centerthe National Science Foundation(Graduate Research Fellowship DGE-1321851)
文摘Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following ner- vous system injury or neurodegenerative disease. Disconnection of axon pathways - the long-distance fibers connecting specialized regions of the central nervous system or relaying peripheral signals - is a common feature of many neurological disorders and injury. However, functional axonal regenera- tion rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engi- neered ＂living scaffolds＂, which are preformed three-dimensional constructs consisting of living neural cells in a defined, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration - mimicking key developmental mechanisms- or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal dusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in predinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery.
文摘检索PubMed、Web of Science、中国知网等数据库中有关喉返神经损伤(RLNI)在甲状腺手术中的研究。关键词包括喉返神经修复、注射喉成形术、Ⅰ型甲状腺成形术、杓状软骨内收术、神经组织工程技术等。总结和比较目前RLNI的常见治疗方法。结果显示,喉返神经直接缝合是目前修复的首选术式,颈袢-喉返神经吻合术最常用于临床,其他修复方式各有其优、缺点。大多数治疗方法可在一定程度上获得不同的效果,但仍存在需进一步克服的缺点。此外神经组织工程技术及中医康复治疗值得进一步探索关注。
