Intrathecal cyclosporin prolongs survival of late-stage ALS mice
Intrathecal cyclosporin prolongs survival of late-stage ALS mice
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DOI：
10.1016/s0006-8993(01)02012-1
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发表时间：
2001-03-16
期刊：
影响因子：
2.9
通讯作者：
Csiszar, K
中科院分区：
文献类型：
--
作者：
Keep, M;Elmér, E;Csiszar, K
肌萎缩侧索硬化症（ALS）是一种神经退行性疾病，其特征是上、下运动神经元死亡伴上行性麻痹导致死亡。在ALS的转基因小鼠模型（SOD 1-G93 A）中，虚弱在3个月大时出现，并且由于进行性瘫痪导致5个月时死亡。环孢菌素A（CsA）因其脑外效应而被公认为器官移植中的免疫抑制剂。当能够进入大脑时，CsA是一种有效的神经保护剂，主要是由于其通过抑制线粒体通透性转换来保护线粒体。CsA不能穿过完整的血脑屏障，在本研究中，CsA通过输注到侧脑室中递送到大脑。注射开始于晚期疾病发作时，后肢明显无力。CsA治疗延长了ALS转基因小鼠的生存期相比，车辆处理的控制。这一发现暗示了ALS中的线粒体功能，并可能对人类疾病具有重要意义。(C)2001 Elsevier Science B. V.保留所有权利。
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by upper and lower motor neuron death with ascending paralysis leading to death. In a transgenic mouse model of ALS (SOD1-G93A) weakness appears at 3 months of age, and because of progressive paralysis leads to death by 5 months. Cyclosporin A (CsA) is well known, for its extracerebral effect, as an immunosuppressant in organ transplantation. When able to access the brain, CsA is an effective neuroprotective agent mainly due to its protection of mitochondria through inhibition of the mitochondrial permeability transition. CsA does not cross the intact blood-brain barrier and was in the present study delivered to the brain through an infusion into the lateral cerebral ventricle. Injections started at the onset of late disease when weakness of the hindlimbs was apparent. CsA treatment prolonged the survival of ALS transgenic mice as compared to vehicle-treated controls. This finding implicates mitochondrial function in ALS and may have significance for human disease. (C) 2001 Elsevier Science B.V. All rights reserved.