title: NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury.
abstract: Neural stem cells (NSCs) in the adult mammalian central nervous system (CNS) hold the key to neural regeneration through proper activation, differentiation, and maturation, to establish nascent neural networks, which can be integrated into damaged neural circuits to repair function. However, the CNS injury microenvironment is often inhibitory and inflammatory, limiting the ability of activated NSCs to differentiate into neurons and form nascent circuits. Here we report that neurotrophin-3 (NT3)-coupled chitosan biomaterial, when inserted into a 5-mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous NSCs in the injured spinal cord. Through slow release of NT3, the biomaterial attracted NSCs to migrate into the lesion area, differentiate into neurons, and form functional neural networks, which interconnected severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis could be a novel strategy for treatment of spinal cord injury.
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; Department of Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China; wack_lily@163.com yi.eve.sun@gmail.com lxgchina@sina.com.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Beijing Friendship Hospital, Capital Medical University, Beijing 100068, China;
authors.forename: Aifeng
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China;
authors.forename: Hongmei
authors.initials: H
authors.lastname: Duan
authors.affiliation: National Center of Biomedical Analysis, Beijing 100850, China;
authors.forename: Sa
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China;
authors.forename: Peng
authors.initials: P
authors.lastname: Hao
authors.affiliation: Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Keqiang
authors.initials: K
authors.lastname: Ye
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital and Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai 200065, China; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095 wack_lily@163.com yi.eve.sun@gmail.com lxgchina@sina.com.
authors.forename: Yi E
authors.initials: YE
authors.lastname: Sun
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; Department of Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China; wack_lily@163.com yi.eve.sun@gmail.com lxgchina@sina.com.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Li
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D060833:Cellular Microenvironment / Q000502:physiology*; D048271:Chitosan / Q000627:therapeutic use; D004576:Electromyography; D005071:Evoked Potentials / Q000502:physiology; D005453:Fluorescence; D007150:Immunohistochemistry; D016253:Microscopy, Immunoelectron; D058953:Neural Stem Cells / Q000187:drug effects* / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects*; D020933:Neurotrophin 3 / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy*
chemical_list: D020933:Neurotrophin 3; D048271:Chitosan
keywords: NT3; chitosan; endogenous neurogenesis; functional recovery; spinal cord injury