1994 Fiscal Year Final Research Report Summary
A Study on Pathophysiology of Amyotrophic Lateral Sclerosis (ALS)
| Project/Area Number |
04404043
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
KIMURA Jun Kyoto University, Department of Neurology, Professor, 医学部, 教授 (10204976)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMOHAMA Shun Kyoto Univ.Dept of Neurology, Lecturer, 医学部, 助手 (60235687)
FUKUYAMA Hidenao Kyoto Univ.Dept of Neurology, Lecturer, 医学部, 講師 (90181297)
KAJI Ryuji Kyoto Univ.Dept of Neurology, Lecturer, 医学部, 講師 (00214304)
AKIGUCHI Ichiro Kyoto Univ.Dept of Neurology, Assistant Professor, 医学部, 助教授 (30115779)
SHIBASAKI Hiroshi Kyoto Univ.Dept of Brain Pathophysiology, Professo, 医学部, 教授 (30037444)
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| Project Period (FY) |
1992 – 1994
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| Keywords | ALS / Multifocal motor neuropathy / Fasciculation / Familial / Central motor program / Dystonia / K channel / Discharge prohability |
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| Research Abstract |
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.
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Research Products
(12 results)
