丙戊酸可改善 SCI 后的体内运动功能，并促进神经元的体外轴突生长。
Valproic acid improves locomotion in vivo after SCI and axonal growth of neurons in vitro.
机构信息
Department of Neurology Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200040, China.
出版信息
Exp Neurol. 2012 Feb;233(2):783-90. doi: 10.1016/j.expneurol.2011.11.042. Epub 2011 Dec 8.
Abstract
Previous studies have found that valproic acid (VPA), a histone deacetylases (HDAC) inhibitor, improves outcomes in a rat model of spinal cord injury (SCI). The study here aimed to further illuminate the neuroprotective effects of VPA against SCI, both in vivo and in vitro. First, spinal cord injury was performed in rats using NYU impactor. Delayed VPA injection (8 h following SCI) significantly accelerated locomotor recovery. VPA therapy also suppressed SCI-induced hypoacetylation of histone and promoted expressions of BDNF and GDNF. Next, the influence of VPA on axonal growth inhibited by a myelin protein was tested. Neurons from embryonic spinal cord or hippocampus were cultured on plates coated with Nogo-A peptide, and escalating concentrations of VPA were added into the cultures. VPA treatment, in a concentration dependent manner, allowed neurons to overcome Nogo-A inhibition of neurite outgrowth. Meanwhile, VPA exposure increased the level of histone acetylation and expression of BDNF in spinal neurons. Cumulatively, these findings indicate that VPA is possibly a promising medication and deserves translational trials for spinal cord injury.
摘要
先前的研究发现，组蛋白去乙酰化酶（HDAC）抑制剂丙戊酸（VPA）可改善脊髓损伤（SCI）大鼠模型的预后。本研究旨在进一步阐明 VPA 对 SCI 的神经保护作用，包括在体内和体外。首先，使用 NYU 撞击器对大鼠进行脊髓损伤。延迟的 VPA 注射（SCI 后 8 小时）显著加速了运动功能的恢复。VPA 治疗还抑制了 SCI 诱导的组蛋白去乙酰化，并促进了 BDNF 和 GDNF 的表达。接下来，研究了 VPA 对髓鞘蛋白抑制的轴突生长的影响。将胚胎脊髓或海马神经元培养在涂有 Nogo-A 肽的平板上，并向培养物中加入不同浓度的 VPA。VPA 处理以浓度依赖的方式使神经元克服了 Nogo-A 对轴突生长的抑制。同时，VPA 暴露增加了脊髓神经元中组蛋白乙酰化水平和 BDNF 的表达。综上所述，这些发现表明 VPA 可能是一种有前途的药物，值得进行脊髓损伤的转化试验。
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