title: Nerve growth factor delivery by ultrasound-mediated nanobubble destruction as a treatment for acute spinal cord injury in rats.
abstract: BACKGROUND
  Spinal cord injuries (SCIs) can cause severe disability or death. Treatment options include surgical intervention, drug therapy, and stem cell transplantation. However, the efficacy of these methods for functional recovery remains unsatisfactory.
  
  
  OBJECTIVE
  This study was conducted to explore the effect of ultrasound (US)-mediated destruction of poly(lactic-co-glycolic acid) (PLGA) nanobubbles (NBs) expressing nerve growth factor (NGF) (NGF/PLGA NBs) on nerve regeneration in rats following SCI.
  
  
  METHODS
  Adult male Sprague Dawley rats were randomly divided into four treatment groups after Allen hit models of SCI were established. The groups were normal saline (NS) group,NGFand NBs group,NGFand US group, andNGF/PLGA NBs and US group. Histological changes after SCI were observed by hematoxylin and eosin staining. Neuron viability was determined by Nissl staining. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was used to examine cell apoptosis. NGF gene and protein expressions were detected by quantitative reverse transcription polymerase chain reaction and Western blotting. Green fluorescent protein expression in the spinal cord was examined using an inverted fluorescence microscope. The recovery of neural function was determined using the Basso, Beattie, and Bresnahan test.
  
  
  RESULTS
  NGFtherapy using US-mediatedNGF/PLGA NBs destruction significantly increased NGF expression, attenuated histological injury, decreased neuron loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in rats with SCI.
  
  
  CONCLUSIONS
  US-mediatedNGF/PLGA NBs destruction effectively transfects theNGFgene into target tissues and has a significant effect on the injured spinal cord. The combination of US irradiation and gene therapy throughNGF/PLGA NBs holds great promise for the future of nanomedicine and the development of noninvasive treatment options for SCI and other diseases.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Song
authors.affiliation: Institution of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital.
authors.forename: Jieliang
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital.
authors.forename: Shengxi
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital.
authors.forename: Zhenming
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000208:Acute Disease; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D019344:Lactic Acid / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D020932:Nerve Growth Factor / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D015203:Reproducibility of Results; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology; D014162:Transfection; D014465:Ultrasonics
chemical_list: D049452:Green Fluorescent Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020932:Nerve Growth Factor
keywords: apoptosis; gene therapy; nanobubbles; nerve growth factor; spinal cord injury