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| LI Xinzhi,YANG Qin,LIN Sen.Effect and mechanism of valproic acid on neurofunctional recovery after acute spinal cord injury in rats[J].Chinese Journal of Spine and Spinal Cord,2012,(4):346-351. |
| Effect and mechanism of valproic acid on neurofunctional recovery after acute spinal cord injury in rats |
| Received:August 25, 2011 Revised:October 20, 2011 |
| English Keywords:Spinal cord injury Valproic acid Nuclear factor kappa B Interleukin 1β Inflammatory reaction Rat |
| Fund:基金项目：成都医学院自然科学基金资助项目（编号：CYZ07-014） |
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| English Abstract: |
| 【Abstract】 Objectives: To investigate the effect and mechanism of valproic acid(VPA) on neurofunctional recovery after acute spinal cord injury(SCI) in rats. Methods: Sixty adult male SD rats were randomly divided into three groups: sham operation group, injury group and VPA treated group. Spinal cord injury model at T10 was maded by modified Allen technique. VPA(300mg/kg) was administrated in rats through hypodermic injection immediately after injury, then repeated per 12h until killing; while sham operation group and injury group received the same dose of normal saline at the same time point. The rats of each group(n=5) were killed at 6h after injury. The recovery of the locomotor function of each group(n=5) was evaluated with Basso，Beattie and Bresnahan(BBB) scale at 24h, 48h, 72h after injury, then the rats were killed. The sections were stained with hematoxylin and eosin(HE) for pathological analyses. The activation of nuclear factor kappa B(NF-κB) was examined by fluorescence double-labeling staining technique and laser scanning confocal microscope. The expression of interleukin 1β(IL-1β) was detected with immunohistochemistry. Results: The BBB score was 21 in sham operation group, and the score in VPA treated group or injury group was significantly lower than that in sham operation group(P<0.05), but the score in VPA treated group was higher than that in injury group at each time point after injury, which showed significant difference at 48h and 72h after injury(P<0.05). The pathological analyses showed the rat spinal cord in sham operation group was normal. In VPA treated group and injury group at 6h after SCI, necrotic neurons and hemorrhagic zone were observed in gray matter, and white matter tracts appeared swollen and edematous. At 24h and 48h after SCI, cystic cavities and inflammatory cell invasion were observed, and the hemorrhagic zone became well defined. At 72h after SCI, the pathological changes were still obvious. Compared with injury group, the pathological changes were similar in VPA treated group at each time point, but inflammatory cell invasion was suppressed in VPA treated group. The NF-κB positive nuclei-stained cell and the expression of IL-1β had never been found or occasionally been found in sham operation group. Compared with sham operation group, the percentage of NF-κB positive nuclei-stained cell and the expression of IL-1β both increased obviously at 6h after SCI(P<0.05), which reached peak at 24h, then decreased, and were still significantly higher at 72h after injury(P<0.05); the percentage of NF-κB positive nuclei-stained cell and the expression of IL-1β evidently decreased in the VPA treated group compared with the injury group at each time point after injury(P<0.05). Conclusions: VPA can promote neurofunctional recovery after spinal cord injury by attenuating inflammatory reaction. |
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