title: Enhanced neuroprotection and improved motor function in traumatized rat spinal cords by rAAV2-mediated glial-derived neurotrophic factor combined with early rehabilitation training.
abstract: BACKGROUND
  Spinal cord injury (SCI) is a serious neurological injury that often leads to permanent disabilities for the victims. The aim of this study was to determine the effects of glial-derived neurotrophic factor (GDNF) mediated by recombinant adeno-associated virus type 2 (rAAV2) alone or in combination with early rehabilitation training on SCI.
  
  
  METHODS
  SCI was induced on the T8-9 segments of the spinal cord by laminectomy in adult male Sprague-Dawley rats. Then besides the sham operation group, the SCI rats were randomly divided into four groups: natural healing group, gene therapy group, rehabilitation training group, and combination therapy group (gene therapy in combination with rehabilitation training). Motor dysfunction, protein expression of GDNF, edema formation, and cell injury were examined 7, 14, and 21 days after trauma.
  
  
  RESULTS
  The topical application of rAAV-GDNF-GFP resulted in strong expression of GDNF, especially after the 14th day, and could protect the motor neuron cells. Early rehabilitative treatment resulted in significantly improved motor function, reduced edema formation, and protected the cells from injury, especially after the 7th and 14th days, and increased the GDNF expression in the damaged area, which was most evident after Day 14. The combined application of GDNF and early rehabilitative treatment after SCI resulted in a significant reduction in spinal cord pathology and motor dysfunction after the 7th and 14th days.
  
  
  CONCLUSIONS
  These observations suggest that rAAV2 gene therapy in combination with rehabilitation therapy has potential clinical value for the treatment of SCI.
authors.affiliation: Department of Physical Education, Suzhou University, Suzhou, Jiangsu 215021, China; Hebei Normal University for Nationalities, Higher Education Park, Chengde, Hebei 067000, China.
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Han
authors.affiliation: Chinese Academy of Sciences Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Chinese Academy of Sciences Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physical Education, Suzhou University, Suzhou, Jiangsu 215021, China.
authors.forename: Hujun
authors.initials: H
authors.lastname: Qiao
authors.affiliation: Department of Physical Education, Suzhou University, Suzhou, Jiangsu 215021, China.
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Chinese Academy of Sciences Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D000229:Dependovirus / Q000235:genetics*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor