RESEARCH

Neurology

Research Summary

1. Human neuropathology
In the field of diagnostic pathology, we perform brain autopsies coming from our university hospital. Our laboratory has a particular interest in neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Lewy body disease and progressive supranuclear palsy. Various types of researches were conducted using these fixed and frozen brain samples. The major types of analyses were immunohistochemistry, confocal microscopy as well as western blotting. We also undertake histopathological diagnosis on the muscle or nerve biopsy tissues from neuromuscular diseases. 
 
2. Oxidtive stress in ALS 
The molecular mechanism of ALS remains unknown. Our laboratory aims to elucidate the mechanism of onset and progression of ALS. The goal of our research is to identify a novel therapeutic target for sporadic ALS patients Recently, it has been reported that stress granules (SGs), which are RNA-containing cytoplasmic foci formed in response to stress exposure, linked to ALS pathology. Furthermore, the exposure to external stress is proposed as a contributor to either disease initiation or the rate of disease progression. As oxidative stress is a major contributory factor to ALS pathology, antioxidant treatments could be a promising therapeutic approach. We now investigate the association between oxidative stress and SGs in ALS pathobiology.
 
3. Analysis of synaptic plasticity in the basal ganglia network by regional quantitation of mRNA in 6-OHDA-lesioned rats
Parkinson’s disease (PD) is a neurodegenerative disease presenting progressive motor dysfunction. Dopaminergic treatment is effective initially, but it becomes less effective and motor complications such as dyskinesia and wearing off appear in the advanced stage of the disease. Not only presynaptic neuronal loss at nigrostriatal dopaminergic synapses, but also postsynaptic dysfunction is considered to cause the decreased effectiveness. Non-dopaminergic neurotransmitters, such as glutamate, endocannabinoids and adenosine have been attracting attention recently to participate in the pathophysiological process of the postsynaptic dysfunction of Parkinson’s disease. To evaluate postsynaptic changes of nigrostriatal dopaminergic synapses, we analysed mRNA expressions of non-dopaminergic neurotransmitter receptors in 6-OHDA-lesioned rats and levodopa-induced dyskinesia (LID) rats.
 
4. Efficacy of pretreatment with edaravone in cerebral hyperperfusion after carotid artery stenting
Cerebral hyperperfusion (CHS) after carotid artery stenting (CAS) is associated with increased morbidity and mortality. Therefore, the prevention of its occurrence would be of clinical value. However, the effective treatment for CHS is not established. A free radical scavenger, edaravone, is widely used for improving functional outcome in patients having acute ischemic stroke. We aim to determine whether pretreatment with edaravone could prevent occurrence of HPS after CAS.