NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury

• Type of Material: Article
• Authors: Zhaoyang Yang, Capital Medical University; Aifeng Zhang, Capital Medical University; Hongmei Duan, Beihang University; Sa Zhang, National Center of Biomedical Analysis; Peng Hao, Capital Medical University; Keqiang Ye, Emory University; Yi E. Sun, Tongji University; Xiaoguang Li, Capital Medical University
• Language: English
• Date: 2015-10-27
• Publisher: NATL ACAD SCIENCES
• Publication Version: Final Published Version
• Copyright Statement: NATIONAL ACADEMY OF SCIENCES
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.1510194112
• Title of Journal or Parent Work: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• Volume: 112
• Issue: 43
• Start Page: 13354
• End Page: 13359
• Grant/Funding Information: This work was supported by the State Key Program of National Natural Science Foundation of China (Grants 31130022, 313101021, 31320103903, 31271037, 81330030, 91319309, and 31271371), the National Science and Technology Pillar Program of China (Grant 2012BAI17B04), the International Cooperation in Science and Technology Projects of the Ministry of Science Technology of China (Grant 2014DFA30640), the National 863 Project (Grant 2012AA020506), the National Ministry of Education Special Fund for Excellent Doctoral Dissertation (Grant 201356), the Special Funds for Excellent Doctoral Dissertation of Beijing, China (Grant 20111000601), the Key Project of the Department of Science and Technology of Beijing (Grant D090800046609004), and the 973 Project (Grant 2012CB966303).
• Keywords: Science & Technology - Other Topics; chitosan; Science & Technology; functional recovery; AXONAL REGENERATION; RAT; NEURAL STEM-CELLS; endogenous neurogenesis; GLYCOPROTEIN; DENTATE GYRUS; EVOKED-POTENTIALS; Multidisciplinary Sciences; PROLIFERATION; MYELIN; DIFFERENTIATION; spinal cord injury; NT3; NEURONS
• Research Categories: Biology, Neuroscience; Psychology, Behavioral

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.