A Study on Pathophysiology of Amyotrophic Lateral Sclerosis (ALS)

肌萎缩侧索硬化症（ALS）的病理生理学研究

基本信息

批准号：
04404043
负责人：
KIMURA Jun
金额：
$ 21.12万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04404043/
关键词：
ALS Multifocal motor neuropathy Fasciculation Familial Central motor program Dystonia K channel Discharge prohability multitocal motor neuropathy fasciculation central motor prosran MMN 一側性上肢筋萎縮症 Fasciculation 血液神経関門ビタミンB_<1

项目摘要

We conducted a series of researches on pathophysiology of ALS and related diseases as well as on basic clinical physiology of central motor control system, which is also the target of disease process in ALS.We found that high-titer anti-GM1 serum from a patient with multifocal motor neuropathy (MMN) can block conduction in single myelinated nerve fiber in vivo through sodium channel blockage. MMN mimics ALS,and may suggest its immunopathogenesis. Some fasciculations in the early ALS were shown to be evoked by magnetic cortical stimulation. This finding indicate that these fasciculations are driven cortically, and that the synaptic efficacy between the upper and lower motor neurons are abnormally enhanced. We also studied the firing probability of lower motor neurons after magnetic cortical stimulation, and firing mediated by the direct corticospinal tract showed disproportionately high probability after the stimulation despite the upper motor neuron loss. These findings suggest glutamate induced excitotoxicity in the early stage of this disease, which warrants a clinical trial with glutamate inhibitor, such as riluzole. We also reported a rare gene mutation in familial ALS in Japan. A part from these, we studied on central motor control in dystonia. Lastly, we found that ultra-high dose vitamin B12 can promote nerve regeneration. This may lead to a potential palliative therapy for patients with ALS.

We conducted a series of researches on pathophysiology of ALS and related diseases as well as on basic clinical physiology of central motor control system, which is also the target of disease process in ALS.We found that high-titer anti-GM1 serum from a patient with multifocal motor neuropathy (MMN) can block conduction in single myelinated nerve fiber in vivo through sodium channel blockage. MMN模拟ALS，并可能暗示其免疫致病发生。早期ALS中的一些痴迷被磁皮质刺激引起。这一发现表明这些束缚是皮层驱动的，并且上下运动神经元之间的突触功效异常增强。我们还研究了磁皮质刺激后较低运动神经元的发射概率，尽管上运动神经元丧失了刺激后，直接皮质脊髓段介导的发射可能显示出高的概率。这些发现表明，谷氨酸在这种疾病的早期诱导兴奋性毒性，该疾病需要用谷氨酸抑制剂（例如riluzole）进行临床试验。我们还报道了日本家族性ALS的罕见基因突变。从这些部分中，我们研究了肌张力障碍中央运动控制。最后，我们发现超高剂量维生素B12可以促进神经再生。这可能会导致对ALS患者的潜在姑息治疗。