Disruption of Neurovascular Unit Prior to Motor Neuron Degeneration in Amyotrophic Lateral Sclerosis
Disruption of Neurovascular Unit Prior to Motor Neuron Degeneration in Amyotrophic Lateral Sclerosis
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DOI：
10.1002/jnr.22594
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发表时间：
2011-05-01
影响因子：
4.2
通讯作者：
Abe, Koji
中科院分区：
文献类型：
--
作者：
Miyazaki, Kazunori;Ohta, Yasuyuki;Abe, Koji
最近的报告表明，血管成分的功能或结构缺陷与肌萎缩侧索硬化症（ALS）的病理学有关。在本研究中，我们研究了一个可能的变化的神经血管单位组成的内皮细胞（PCAM-1），紧密连接（occludin），和基底膜（胶原IV）在ALS患者和ALS模型小鼠MMP-9的可能激活。我们发现ALS模型小鼠的神经血管单位的损害在外侧更突出，并且优先在前角。这种损伤发生在运动神经元变性之前，并伴有MMP-9的上调。我们还发现，在人类和ALS动物模型中，PCAM-1阳性内皮细胞和GFAP阳性星形胶质细胞足突之间存在解离。目前的研究结果表明，血管周围的损害先于疾病的顺序变化，这是在人类和ALS的动物模型之间的共同点，这表明神经血管单位是一个潜在的目标，在ALS的治疗干预。(C)2011 Wiley-Liss，Inc.
Recent reports suggest that functional or structural defect of vascular components are implicated in amyotrophic lateral sclerosis (ALS) pathology. In the present study, we examined a possible change of the neurovascular unit consisting of endothelium (PCAM-1), tight junction (occludin), and basement membrane (collagen IV) in relation to a possible activation of MMP-9 in ALS patients and ALS model mice. We found that the damage in the neurovascular unit was more prominent in the outer side and preferentially in the anterior horn of ALS model mice. This damage occurred prior to motor neuron degeneration and was accompanied by MMP-9 up-regulation. We also found the dissociation between the PCAM-1-positive endothelium and GFAP-positive astrocyte foot processes in both humans and the animal model of ALS. The present results indicate that perivascular damage precedes the sequential changes of the disease, which are held in common between humans and the animal model of ALS, suggesting that the neurovascular unit is a potential target for therapeutic intervention in ALS. (C) 2011 Wiley-Liss, Inc.