Reducing host aldose reductase activity promotes neuronal differentiation of transplanted neural stem cells at spinal cord injury sites and facilitates locomotion recovery

作     者：Kun Zhang Wen-Can Lu Ming Zhang Qian Zhang Pan-Pan Xian Fang-Fang Liu Zhi-Yang Chen Chung Sookja Kim Sheng-Xi Wu Hui-Ren Tao Ya-Zhou Wang Kun Zhang;Wen-Can Lu;Ming Zhang;Qian Zhang;Pan-Pan Xian;Fang-Fang Liu;Zhi-Yang Chen;Chung Sookja Kim;Sheng-Xi Wu;Hui-Ren Tao;Ya-Zhou Wang

作者机构：Department of Neurobiology and Institute of NeurosciencesSchool of Basic MedicineFourth Military Medical UniversityXi’anShaanxi ProvinceChina Key Laboratory of Spine and Spinal Cord Injury Repair and RegenerationTongji UniversityShanghaiChina Department of Spine SurgeryShenzhen University General HospitalShenzhenGuangdong ProvinceChina Department of NeurologyHainan Hospital of Chinese PLA General HospitalSanyaHainan ProvinceChina Department of AnesthesiologyTangdu HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina Faculty of MedicineMacao University of Science and TechnologyMacao Special Administrative RegionChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2022年第17卷第8期

页      面：1814-1820页

核心收录：

学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China,Nos.81601056(to KZ),81901252(to QZ) Shaanxi Key Research and Development Program of China,No.2020SF-083(to KZ) Sanming Project of Medicine in Shenzhen of China,No.SZSM201911011(to SXW) the Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration(Tongji University,Ministry of Education)of China(to KZ) 

主　　题：aldose reductase functional recovery inflammation macrophage microglia neural stem cell transplantation neuronal differentiation polarization spinal cord injury 

摘      要：Neural stem cell(NSC)transplantation is a promising strategy for replacing lost neurons following spinal cord ***,the survival and differentiation of transplanted NSCs is limited,possibly owing to the neurotoxic inflammatory *** of the important role of glucose metabolism in M1/M2 polarization of microglia/macrophages,we hypothesized that altering the phenotype of microglia/macrophages by regulating the activity of aldose reductase(AR),a key enzyme in the polyol pathway of glucose metabolism,would provide a more beneficial microenvironment for NSC survival and ***,we reveal that inhibition of host AR promoted the polarization of microglia/macrophages toward the M2 phenotype in lesioned spinal cord injuries.M2 macrophages promoted the differentiation of NSCs into neurons in *** of NSCs into injured spinal cords either deficient in AR or treated with the AR inhibitor sorbinil promoted the survival and neuronal differentiation of NSCs at the injured spinal cord site and contributed to locomotor functional *** findings suggest that inhibition of host AR activity is beneficial in enhancing the survival and neuronal differentiation of transplanted NSCs and shows potential as a treatment of spinal cord injury.