title: Neuroprotective ferulic acid (FA)-glycol chitosan (GC) nanoparticles for functional restoration of traumatically injured spinal cord.
abstract: An urgent unmet need exists for early-stage treatment of spinal cord injury (SCI). Currently methylprednisolone is the only therapeutic agent used in clinics, for which the efficacy is controversial and the side effect is well-known. We demonstrated functional restoration of injured spinal cord by self-assembled nanoparticles composed of ferulic acid modified glycol chitosan (FA-GC). Chitosan and ferulic acid are strong neuroprotective agents but their systemic delivery is difficult. Our data has shown a prolonged circulation time of the FA-GC nanoparticles allowing for effective delivery of both chitosan and ferulic acid to the injured site. Furthermore, the nanoparticles were found both in the gray matter and white matter. The in vitro tests demonstrated that nanoparticles protected primary neurons from glutamate-induced excitotoxicity. Using a spinal cord contusion injury model, significant recovery in locomotor function was observed in rats that were intravenously administered nanoparticles at 2 h post injury, as compared to non-improvement by methylprednisolone administration. Histological analysis revealed that FA-GC treatment significantly preserved axons and myelin and also reduced cavity volume, astrogliosis, and inflammatory response at the lesion site. No obvious adverse effects of nanoparticles to other organs were found. The restorative effect of FA-GC presents a promising potential for treating human SCIs.
authors: Department of Neurobiology, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
authors: Wei
authors: W
authors: Wu
authors: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907.
authors: Seung-Young
authors: SY
authors: Lee
authors: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery, Department of Anatomy and Cell Biology, Goldman and Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202.
authors: Xiangbing
authors: X
authors: Wu
authors: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907.
authors: Jacqueline Y
authors: JY
authors: Tyler
authors: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907.
authors: He
authors: H
authors: Wang
authors: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907.
authors: Zheng
authors: Z
authors: Ouyang
authors: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907.
authors: Kinam
authors: K
authors: Park
authors: Department of Neurobiology, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.|Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery, Department of Anatomy and Cell Biology, Goldman and Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN 46202.
authors: Xiao-Ming
authors: XM
authors: Xu
authors: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907.|Department of Chemistry, Purdue University, West Lafayette, IN 47907.
authors: Ji-Xin
authors: JX
authors: Cheng
mesh_terms: D000818:Animals; D001682:Biological Availability; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D003373:Coumaric Acids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008124:Locomotion; D008297:Male; D053758:Nanoparticles; D018696:Neuroprotective Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D003373:Coumaric Acids; D018696:Neuroprotective Agents; D048271:Chitosan; C004999:ferulic acid
keywords: Anti-excitotoxicity; Ferulic acid; Functional restoration; Glycol chitosan; Neuroprotective polymer; Spinal cord injury