Improved outcome of EAN, an animal model of GBS, through amelioration of peripheral and central inflammation by minocycline.
Improved outcome of EAN, an animal model of GBS, through amelioration of peripheral and central inflammation by minocycline.
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DOI：
10.1111/j.1582-4934.2008.00333.x
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发表时间：
2009-02
影响因子：
5.3
通讯作者：
Schluesener HJ
中科院分区：
文献类型：
--
作者：
Zhang ZY;Zhang Z;Fauser U;Schluesener HJ
实验性自身免疫性神经炎（EAN）是一种广泛使用的人类急性炎性脱髓鞘性多神经根神经病的动物模型，是格林-巴利综合征最常见的亚型。EAN的病理特征是血-神经屏障的破坏、反应性免疫细胞的浸润、局部炎症、周围神经系统中的脱髓鞘和机械性异常性疼痛。米诺环素已知具有神经保护和抗炎作用。此外，在多种动物模型中观察到米诺环素给药后神经性疼痛的缓解。在这里，我们研究了米诺环素对大鼠EAN的影响。米诺环素（50毫克/公斤体重，每天立即免疫后）的抑制治疗显着减弱EAN的严重程度和持续时间。与磷酸盐缓冲盐水（PBS）处理的EAN大鼠相比，用米诺环素处理的EAN大鼠坐骨神经中的巨噬细胞和T细胞浸润和脱髓鞘显著减少。二甲胺四环素能显著降低EAN大鼠坐骨神经中基质金属肽酶9、诱导型一氧化氮合酶、促炎细胞因子白细胞介素1 β和肿瘤坏死因子α的mRNA表达。此外，米诺环素减轻EAN大鼠的机械异常性疼痛，并大大抑制脊髓小胶质细胞的激活。总之，我们的数据表明，米诺环素可以有效地抑制外周和脊髓炎症（免疫激活），以改善EAN大鼠的结局，这表明米诺环素可能被认为是一个潜在的候选药物治疗自身免疫介导的神经病变。
Experimental autoimmune neuritis (EAN) is a widely used animal model of the human acute inflammatory demyelinating polyradiculoneuropathy, which is the most common subtype of Guillain-Barré Syndrome. EAN is pathologically characterized by breakdown of the blood-nerve barrier, infiltration of reactive immune cells, local inflammation, demyelination in the peripheral nervous system and mechanical allodynia. Minocycline is known to have neuroprotective and anti-inflammatory effects. Furthermore, relieve of neuropathic pain following minocycline administration was observed in a variety of animal models. Here, we investigated the effects of minocycline on rat EAN. Suppressive treatment with minocycline (50 mg/kg body weight daily immediately after immunization) significantly attenuated the severity and duration of EAN. Macrophage and T-cell infiltration and demyelination in sciatic nerves of EAN rats treated with minocycline were significantly reduced compared to phosphate-buffered saline (PBS)-treated EAN rats. mRNA expressions of matrix metallopeptidase-9, inducible nitric oxide synthase and pro-inflammatory cytokines interleukin-1 β and tumour necrosis factor-α in EAN sciatic nerves were greatly decreased by administration of minocycline as well. Furthermore, minocycline attenuated mechanical allodynia in EAN rats and greatly suppressed spinal microglial activation. All together, our data showed that minocycline could effectively suppress the peripheral and spinal inflammation (immune activation) to improve outcome in EAN rats, which suggests that minocycline may be considered as a potential candidate of pharmacological treatment for autoimmune-mediated neuropathies.
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影响因子：
4.2
作者：
Pannu, R;Barbosa, E;Singh, I
通讯作者：
Singh, I
影响因子：
7.4
作者：
Ledeboer, A;Sloane, EM;Watkins, LR
通讯作者：
Watkins, LR
DOI：
10.1016/0162-3109(95)00041-0
发表时间：
1996-03-01
期刊：
IMMUNOPHARMACOLOGY
影响因子：
--
作者：
Kloppenburg, M;Dijkmans, BAC;Breedveld, FC
通讯作者：
Breedveld, FC
DOI：
10.1016/s1357-4310(99)01639-1
发表时间：
2000-02-01
期刊：
MOLECULAR MEDICINE TODAY
影响因子：
--
作者：
Gold, R;Hartung, HP;Toyka, KV
通讯作者：
Toyka, KV
影响因子：
6.2
作者：
Nasu-Tada, K;Koizumi, S;Inoue, K
通讯作者：
Inoue, K