Yu Song-Hee, Cho Dae-Chul, Kim Kyoung-Tae, Nam Kyung-Hun, Cho Hee-Jung, Sung Joo-Kyung
Department of Neurosurgery, School of Medicine, Kyungpook National University, Daegu, Korea.
J Korean Neurosurg Soc. 2012 Apr;51(4):191-8. doi: 10.3340/jkns.2012.51.4.191. Epub 2012 Apr 30.
Valproic acid (VPA), as known as histone deacetylase inhibitor, has neuroprotective effects. This study investigated the histological changes and functional recovery from spinal cord injury (SCI) associated with VPA treatment in a rat model.
Locomotor function was assessed according to the Basso-Beattie-Bresnahan scale for 2 weeks in rats after receiving twice daily intraperitoneal injections of 200 mg/kg VPA or the equivalent volume of normal saline for 7 days following SCI. The injured spinal cord was then examined histologically, including quantification of cavitation.
Basso-Beattie-Bresnahan scale scores in rats receiving VPA were significantly higher than in the saline group (p<0.05). The cavity volume in the VPA group was significantly reduced compared with the control (saline-injected) group (p<0.05). The level of histone acetylation recovered in the VPA group, while it was significantly decreased in the control rats (p<0.05). The macrophage level was significantly decreased in the VPA group (p<0.05).
VPA influences the restoration of hyperacetylation and reduction of the inflammatory reaction resulting from SCI, and is effective for histology and motor function recovery.
丙戊酸(VPA)作为一种组蛋白去乙酰化酶抑制剂,具有神经保护作用。本研究在大鼠模型中探究了与VPA治疗相关的脊髓损伤(SCI)后的组织学变化和功能恢复情况。
在脊髓损伤后,对大鼠每日进行两次腹腔注射200mg/kg VPA或等量生理盐水,持续7天,之后根据Basso-Beattie-Bresnahan量表评估大鼠运动功能,为期2周。然后对损伤的脊髓进行组织学检查,包括空洞量化分析。
接受VPA治疗的大鼠的Basso-Beattie-Bresnahan量表评分显著高于生理盐水组(p<0.05)。与对照组(注射生理盐水组)相比,VPA组的空洞体积显著减小(p<0.05)。VPA组的组蛋白乙酰化水平恢复,而对照组大鼠的组蛋白乙酰化水平显著降低(p<0.05)。VPA组的巨噬细胞水平显著降低(p<0.05)。
VPA影响SCI后高乙酰化的恢复和炎症反应的减轻,对组织学和运动功能恢复有效。