Enhanced neuroprotection and improved motor function in traumatized rat spinal cords by rAAV2-mediated glial-derived neurotrophic factor combined with early rehabilitation training.

Qingquan Han; Jingjing Xiang; Yun Zhang; Hujun Qiao; Yongwei Shen; Chun Zhang

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Enhanced neuroprotection and improved motor function in traumatized rat spinal cords by rAAV2-mediated glial-derived neurotrophic factor combined with early rehabilitation training.

Author: Qingquan HAN ^{1
,

2} ; Jingjing XIANG ³ ; Yun ZHANG ³ ; Hujun QIAO ⁴ ; Yongwei SHEN ⁴ ; Chun ZHANG ³
Author Information

1. Department of Physical Education, Suzhou University, Suzhou, Jiangsu 215021, China
2. Hebei Normal University for Nationalities, Higher Education Park, Chengde, Hebei 067000, China.
3. 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.
4. Department of Physical Education, Suzhou University, Suzhou, Jiangsu 215021, China.
Publication Type:Journal Article
MeSH: Animals; Cell Line; Dependovirus; genetics; Glial Cell Line-Derived Neurotrophic Factor; genetics; physiology; Humans; Immunohistochemistry; Male; Motor Activity; genetics; physiology; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; metabolism
From: Chinese Medical Journal 2014;127(24):4220-4225
CountryChina
Language:English
Abstract:
BACKGROUNDSpinal 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.
METHODSSCI 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.
RESULTSThe 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.
CONCLUSIONThese observations suggest that rAAV2 gene therapy in combination with rehabilitation therapy has potential clinical value for the treatment of SCI.