Chronic spinal cord injury repair by NT3-chitosan only occurs after clearance of the lesion scar  

作　　者：Can Zhao Jia-Sheng Rao Hongmei Duan Peng Hao Junkui Shang Yubo Fan Wen Zhao Yudan Gao Zhaoyang Yang Yi Eve Sun Xiaoguang Li 

机构地区：[1]Beijing Key Laboratory for Biomaterials and Neural Regeneration,Beijing Advanced Innovation Center for Biomedical Engineering,School of Biological Science and Medical Engineering,Beihang University,Beijing 100083,China [2]Institute of Rehabilitation Engineering,China Rehabilitation Science Institute,Beijing 100068,China [3]Department of Neurobiology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China [4]Beijing Advanced Innovation Centre for Biomedical Engineering,Key Laboratory for Biomechanics and Mechanobiology of Chinese Education Ministry,School of Biological Science and Medical Engineering,Beihang University,Beijing 10083,China [5]School of Engineering Medicine,Beihang University,Beijing 10083,China [6]Shanghai Institute of Stem Cell Research and Clinical Translation,Shanghai East Hospital,Tongji University School of Medicine,Shanghai 200120,China [7]Department of Psychiatry and Biobehavioral Sciences,UCLA Medical School,Los Angeles,CA 90095,USA

出　　处：《Signal Transduction and Targeted Therapy》2022年第7期2568-2580,共13页信号转导与靶向治疗（英文）

基　　金：supported by Ministry of Science and Technology of China(Grants 2017YFC1104001,2017YFC1104002,2020YFC2002804);National Natural Science Foundation of China(Grants 31900980,31970970,31730030,81941011,31971279,31771053,82030035,31900749);Beijing Science and Technology Program(Grant Z181100001818007);Natural Science Foundation of Beijing Municipality(Grant KZ201810025030,7222004);Priority of Shanghai Key Discipline of Medicine(Grant 2017ZZ02020);Foundation of Shanghai Municipal Education Commission(Grant 2019-01-07-00-07-E00055);the Key R&D Program of Jiangsu(Grant BE2020026);Fundamental Research Funds for Central Public Welfare Research Institutes(Grant 2022CZ-12).

摘　　要：Spinal cord injury(SCI)is a severe damage usually leading to limb dysesthesia,motor dysfunction,and other physiological disability.We have previously shown that NT3-chitosan could trigger an acute SCI repairment in rats and non-human primates.Due to the negative effect of inhibitory molecules in glial scar on axonal regeneration,however,the role of NT3-chitosan in the treatment of chronic SCI remains unclear.Compared with the fresh wound of acute SCI,how to handle the lesion core and glial scars is a major issue related to chronic-SCI repair.Here we report,in a chronic complete SCI rat model,establishment of magnetic resonancediffusion tensor imaging(MR-DTI)methods to monitor spatial and temporal changes of the lesion area,which matched well with anatomical analyses.Clearance of the lesion core via suction of cystic tissues and trimming of solid scar tissues before introducing NT3-chitosan using either a rigid tubular scaffold or a soft gel form led to robust neural regeneration,which interconnected the severed ascending and descending axons and accompanied with electrophysiological and motor functional recovery.In contrast,cystic tissue extraction without scar trimming followed by NT3-chitosan injection,resulted in little,if any regeneration.Taken together,after lesion core clearance,NT3-chitosan can be used to enable chronic-SCI repair and MR-DTI-based mapping of lesion area and monitoring of ongoing regeneration can potentially be implemented in clinical studies for subacute/chronic-SCI repair.

关 键 词：SCAR NT3 WOUND 

分 类 号：R68[医药卫生—骨科学]