title: Angiogenic microspheres promote neural regeneration and motor function recovery after spinal cord injury in rats.
abstract: This study examined sustained co-delivery of vascular endothelial growth factor (VEGF), angiopoietin-1 and basic fibroblast growth factor (bFGF) encapsulated in angiogenic microspheres. These spheres were delivered to sites of spinal cord contusion injury in rats, and their ability to induce vessel formation, neural regeneration and improve hindlimb motor function was assessed. At 2-8 weeks after spinal cord injury, ELISA-determined levels of VEGF, angiopoietin-1, and bFGF were significantly higher in spinal cord tissues in rats that received angiogenic microspheres than in those that received empty microspheres. Sites of injury in animals that received angiogenic microspheres also contained greater numbers of isolectin B4-binding vessels and cells positive for nestin or β III-tubulin (P < 0.01), significantly more NF-positive and serotonergic fibers, and more MBP-positive mature oligodendrocytes. Animals receiving angiogenic microspheres also suffered significantly less loss of white matter volume. At 10 weeks after injury, open field tests showed that animals that received angiogenic microspheres scored significantly higher on the Basso-Beattie-Bresnahan scale than control animals (P < 0.01). Our results suggest that biodegradable, biocompatible PLGA microspheres can release angiogenic factors in a sustained fashion into sites of spinal cord injury and markedly stimulate angiogenesis and neurogenesis, accelerating recovery of neurologic function.
authors.affiliation: Department of Neurobiology, Beijing Institute for Brain Disorders, Beijing Center of Neural Regeneration and Repair, Beijing Key Laboratory of Major Brain Disorders, Capital Medical University, 10 Xitoutiao, You An Men, Beijing 100069, China.
authors.forename: Shukui
authors.initials: S
authors.lastname: Yu
authors.affiliation: School of Materials Science and Engineering, University of Science and Technology Beijing, 30 Xueyuan Road, Beijing 100083, China.|School of Materials Science and Engineering, Tsinghua University, Hai Dian, Beijing 100084, China.
authors.forename: Shenglian
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Neurobiology, Beijing Institute for Brain Disorders, Beijing Center of Neural Regeneration and Repair, Beijing Key Laboratory of Major Brain Disorders, Capital Medical University, 10 Xitoutiao, You An Men, Beijing 100069, China.|Ningxia Key Laboratory of Cerebrocranial Diseases, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750004, China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Department of Anatomy, School of Basic Medical Sciences, Capital Medical University, 10 Xitoutiao, You An Men, Beijing 100069, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anatomy, School of Basic Medical Sciences, Capital Medical University, 10 Xitoutiao, You An Men, Beijing 100069, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Beijing Institute for Brain Disorders, Beijing Center of Neural Regeneration and Repair, Beijing Key Laboratory of Major Brain Disorders, Capital Medical University, 10 Xitoutiao, You An Men, Beijing 100069, China.
authors.forename: Qunyuan
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000818:Animals; D016880:Anisotropy; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D036384:Ephrin-A3 / Q000378:metabolism; D005260:Female; D019344:Lactic Acid / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008863:Microspheres; D009043:Motor Activity / Q000502:physiology*; D018919:Neovascularization, Physiologic; D009416:Nerve Regeneration / Q000502:physiology*; D058953:Neural Stem Cells / Q000378:metabolism; D009929:Organ Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D015854:Up-Regulation / Q000235:genetics; D066127:White Matter / Q000473:pathology / Q000503:physiopathology
chemical_list: D036384:Ephrin-A3; C546388:MIRN210 microRNA, rat; D035683:MicroRNAs; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid