Clinical Neuroscience and Therapeutics

Prof. Hirofumi Maruyama

【Research Keyword】
Cerebrovascular disease, amyotrophic lateral sclerosis, Alzheimer disease, Parkinson disease, neurodegenerative disease, neurosonology, biomarker

【Recent highlights】
We have been studying optineurin, the gene responsible for amyotrophic lateral sclerosis (ALS), which was identified at Hiroshima University. We reported that knockdown of optineurin in myoblasts has revealed that optineurin is involved in muscle differentiation. ALS is widely known as a disease caused by degeneration of nerves, and this finding suggests that some abnormality also occurs in muscle.
We also reported that oligomers of amyloid-β, one of the causative proteins of Alzheimer's disease (AD), are internalized into neurons by a mechanism called micropinocytosis, which contribute to the elucidation of the pathology of AD.
Using next-generation sequencing, we have identified genetic risk factors for Parkinson's disease in Japanese patients.
In collaboration with dentistry, our laboratory has examined factors related to the oral environment and stroke pathophysiology and outcome, and identified various specific periodontal species related to stroke outcome, cerebral small vessel disease status, hematoma expansion in cerebral hemorrhage, and presence of atrial fibrillation. We have also identified nutritional status and tooth loss status as being related to stroke outcome. We are also actively conducting multicenter epidemiological studies and have established a stroke registry study (HARP study) at affiliated hospitals in Hiroshima City. We are also conducting a multicenter study of stroke related to malignant tumors and reporting on blood biomarkers related to pathophysiology and prognosis.
Neurological diseases often cause feeding and swallowing disorders, and we have achieved a great deal of success in clinical research aimed at avoiding the risk of such disorders. In particular, we reported the usefulness of tongue pressure measurement and cough test for assessing aspiration risk in stroke, and proposed an index of tongue pressure value for providing safe eating patterns.
In the study of neurosonology, we clarified reference values for nerve cross-sectional area in lower extremity peripheral nerve echo, in addition to the previously reported reference values for upper extremity peripheral nerves, focusing on anatomical aspects such as nerve branching and confluence.

Profiles of Faculty and Research Scholars

1.Clinical neurology(cerebrovascular disease, neurodegenerative disease, neuroimmunological disease, epilepsy, neuromuscular disease etc)
2.Clinical neuroscience (J-STARS, neurosonology)
3.Basic neuroscience (neuropathology, molecular biology, molecular genetics)

1. Clinical research group:
 (1) Stroke: Clinical application of neuro-ultrasound, neuroradiological imaging, and blood biomarkers. Promotion of multicenter collaborative research. Themes include oral environment and stroke, nutritional status and stroke, cerebral microvascular disease, autonomic nervous system changes and stroke.
 (2) Neurodegenerative diseases: In addition to various studies on diagnosis and treatment of neurodegenerative diseases, we are conducting a multicenter observational study (CARP Study: Chugoku ALS Retrospective Study), including disease state analysis, to elucidate the pathophysiology of ALS.
 (3) Immunological neurological diseases (peripheral neuropathies such as chronic inflammatory demyelinating polyneuropathy and Guillain-Barre syndrome, myasthenia gravis, multiple sclerosis, neuromyelitis optica spectrum disorders, anti-MOG antibody-related diseases, etc.): Clinical diagnosis and biomarker search for disease status (Neuroimaging including such as neurosonography and MRI) and epidemiological studies. Multicenter collaborative research is also being undertaken.
 (4) Epilepsy: Mapping of brain function using broadband cortical EEG and focal epilepsy analysis in patients with refractory epilepsy, multicenter studies of pathophysiology and prognosis in critical care EEG in acute brain diseases, and epidemiological studies using the epilepsy registry in Hiroshima City.
 (5) Feeding and swallowing nutrition: Early detection of dysphagia by tongue depressor, search for appropriate markers to evaluate nutritional status (e.g. CONUT score), and prevention of aspiration pneumonia through team medicine intervention including dentists.
2. Molecular Neuroscience Research Group: The group evaluates functions at the gene and protein level related to the pathogenesis of neurodegenerative diseases such as AD, Parkinson's disease, and spinocerebellar degeneration. The knockout mouse/knockin cell and animal models are generated, and through functional analysis and pathological studies, the molecular pathological mechanisms involved in each disease are elucidated and the development of new therapeutic methods and biomarkers are explored.
3. Molecular genetic research group: Genetic analysis for neurodegenerative disease.