Effect of geranylgeranylacetone on optic neuritis in experimental autoimmune encephalomyelitis
Effect of geranylgeranylacetone on optic neuritis in experimental autoimmune encephalomyelitis
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DOI：
10.1016/j.neulet.2009.07.028
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发表时间：
2009-09-25
影响因子：
2.5
通讯作者：
Harada, Takayuki
中科院分区：
文献类型：
--
作者：
Guo, Xiaoli;Harada, Chikako;Harada, Takayuki
视神经炎是一种中枢神经系统（CNS）的急性炎性脱髓鞘综合征，常发生于多发性硬化症（MS）。由于它可以导致不可逆的视力丧失，特别是在视脊髓形式的MS或视神经肌萎缩症（NMO），本研究进行了评估香叶基香叶基丙酮（GGA）对视神经炎的MS的实验性自身免疫性脑脊髓炎（EAE）小鼠模型的影响。髓鞘少突胶质细胞糖蛋白诱导的EAE小鼠接受口服GGA 500 mg/kg或车辆，每天一次，持续22天。在第22天通过形态学分析检查GGA对视神经炎严重程度的影响。采用多焦视网膜电图（mfERG）检测视功能。此外，从临床体征和形态学方面监测GGA对肌萎缩严重程度的影响。通过mfERG的第二内核评估的视觉功能在GGA处理的小鼠中与溶剂处理的小鼠相比显著改善。GGA治疗减少了视神经中变性轴突的数量，并防止了视网膜神经节细胞层中的细胞损失。然而，脊髓中脱髓鞘的严重程度不受GGA治疗的影响。这些结果表明，口服GGA对MS的EAE小鼠模型中的视神经炎治疗具有有益作用。（c）2009 Elsevier爱尔兰有限公司保留所有权利。
Optic neuritis is an acute inflammatory demyelinating syndrome of the central nervous system (CNS) that often occurs in multiple sclerosis (MS). Since it can cause irreversible visual loss, especially in the optic-spinal form of MS or neuromyelitis optica (NMO), the present study was conducted to assess the effects of geranylgeranylacetone (GGA) on optic neuritis in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Myelin oligodendrocyte glycoprotein-induced EAE mice received oral administration of GGA at 500 mg/kg or vehicle once daily for 22 days. The effects of GGA on the severity of optic neuritis were examined by morphological analysis on day 22. Visual functions were measured by the multifocal electroretinograms(mfERG). In addition, the effects of GGA on severity of myelitis were monitored both on clinical signs and morphological aspects. The visual function, as assessed by the second-kernel of mfERG, was significantly improved in GGA-treated mice compared with vehicle-treated mice. GGA treatment decreased the number of degenerating axons in the optic nerve and prevented cell loss in the retinal ganglion cell layer. However, the severity of demyelination in the spinal cord remained unaffected with the treatment of GGA. These results suggest that oral GGA administration has beneficial effect on the treatment for optic neuritis in the EAE mouse model of MS. (c) 2009 Elsevier Ireland Ltd. All rights reserved.