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Article ; Online: Role of the Gut Microbiota in Stroke Pathogenesis and Potential Therapeutic Implications.

Yamashiro, Kazuo / Kurita, Naohide / Urabe, Takao / Hattori, Nobutaka

2021 Volume 77 Suppl 2, Page(s) 36–44

Abstract: Background: Major advances have been made in stroke treatment and prevention in the past decades. However, the burden of stroke remains high. Identification of novel targets and establishment of effective interventions to improve stroke outcomes are, ... ...

Abstract	Background: Major advances have been made in stroke treatment and prevention in the past decades. However, the burden of stroke remains high. Identification of novel targets and establishment of effective interventions to improve stroke outcomes are, therefore, needed. Recent research highlights the contribution of the gut microbiota to stroke pathogenesis. Summary: Compositional and functional alterations of the gut microbiota, termed dysbiosis, are linked to stroke risk factors, such as obesity, metabolic diseases, and atherosclerosis. In acute cerebral ischemia, the gut microbiota plays a key role in bidirectional interactions between the gut and brain, referred to as the microbiota-gut-brain axis. Gut dysbiosis prior to ischemic stroke affects outcomes. Additionally, the brain affects the gut microbiota during acute ischemic brain injury, which in turn impacts outcomes. Interactions between the gut microbiota and stroke pathogenesis are mediated by several factors including bacterial components (e.g., lipopolysaccharide), gut microbiota-related metabolites (e.g., short-chain fatty acids and trimethylamine N-oxide), and the immune and nervous systems. Clinical studies have reported that patients with acute ischemic stroke exhibit gut dysbiosis, which is associated with host metabolism and inflammation, as well as functional outcomes. Modulation of the gut microbiota or its metabolites improves conditions related to stroke pathogenesis, including inflammation, cardiometabolic disease, atherosclerosis, and thrombosis. Key Messages: Accumulating evidence indicates that the gut microbiota plays a possible role in stroke pathogenesis. Modulation of the gut microbiota may provide a novel therapeutic strategy for the treatment and prevention of stroke.
MeSH term(s)	Bacteria ; Dysbiosis ; Gastrointestinal Microbiome ; Humans ; Ischemic Stroke ; Stroke/etiology ; Stroke/therapy
Language	English
Publishing date	2021-06-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	392341-1
ISSN	1421-9697 ; 0250-6807 ; 1018-9688
ISSN (online)	1421-9697
ISSN	0250-6807 ; 1018-9688
DOI	10.1159/000516398
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Article ; Online: Response to the letter by Kazuo Yamashiro.

Yamashiro, Kazuo

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association

2013 Volume 22, Issue 6, Page(s) 895–896

MeSH term(s)	Cerebral Hemorrhage/diagnosis ; Diffusion Magnetic Resonance Imaging ; Female ; Humans ; Microscopic Polyangiitis/complications
Language	English
Publishing date	2013-08
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	1131675-5
ISSN	1532-8511 ; 1052-3057
ISSN (online)	1532-8511
ISSN	1052-3057
DOI	10.1016/j.jstrokecerebrovasdis.2013.06.028
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Article ; Online: Correction to: Astrocytic Extracellular Vesicles Regulated by Microglial Inflammatory Responses Improve Stroke Recovery.

Kijima, Chikage / Inaba, Toshiki / Hira, Kenichiro / Miyamoto, Nobukazu / Yamashiro, Kazuo / Urabe, Takao / Hattori, Nobutaka / Ueno, Yuji

Molecular neurobiology

2023 Volume 61, Issue 2, Page(s) 1022

Language	English
Publishing date	2023-09-20
Publishing country	United States
Document type	Published Erratum
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-023-03657-5
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Article ; Online: Astrocytic Extracellular Vesicles Regulated by Microglial Inflammatory Responses Improve Stroke Recovery.

Kijima, Chikage / Inaba, Toshiki / Hira, Kenichiro / Miyamoto, Nobukazu / Yamashiro, Kazuo / Urabe, Takao / Hattori, Nobutaka / Ueno, Yuji

Molecular neurobiology

2023 Volume 61, Issue 2, Page(s) 1002–1021

Abstract: There are no effective treatments for post-stroke glial scar formation, which inhibits axonal outgrowth and functional recovery after stroke. We investigated whether astrocytic extracellular vesicles (AEVs) regulated by microglia modulate glial scars and ...

Abstract	There are no effective treatments for post-stroke glial scar formation, which inhibits axonal outgrowth and functional recovery after stroke. We investigated whether astrocytic extracellular vesicles (AEVs) regulated by microglia modulate glial scars and improve stroke recovery. We found that peri-infarct glial scars comprised reactive astrocytes with proliferating C3d and decreased S100A10 expression in chronic stroke. In cultured astrocytes, microglia-conditioned media and treatment with P2Y
MeSH term(s)	Rats ; Animals ; Microglia/metabolism ; NF-kappa B/metabolism ; Astrocytes/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Gliosis/pathology ; Stroke/pathology ; Extracellular Vesicles/metabolism
Chemical Substances	NF-kappa B ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2023-09-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-023-03629-9
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Article ; Online: Free water in gray matter linked to gut microbiota changes with decreased butyrate producers in Alzheimer's disease and mild cognitive impairment.

Yamashiro, Kazuo / Takabayashi, Kaito / Kamagata, Koji / Nishimoto, Yuichiro / Togashi, Yuka / Yamauchi, Yohsuke / Ogaki, Kotaro / Li, Yuanzhe / Hatano, Taku / Motoi, Yumiko / Suzuki, Michimasa / Miyakawa, Koichi / Ishikawa, Dai / Aoki, Shigeki / Urabe, Takao / Hattori, Nobutaka

Neurobiology of disease

2024 Volume 193, Page(s) 106464

Abstract: Neuroinflammation contributes to the pathology and progression of Alzheimer's disease (AD), and it can be observed even with mild cognitive impairment (MCI), a prodromal phase of AD. Free water (FW) imaging estimates the extracellular water content and ... ...

Abstract	Neuroinflammation contributes to the pathology and progression of Alzheimer's disease (AD), and it can be observed even with mild cognitive impairment (MCI), a prodromal phase of AD. Free water (FW) imaging estimates the extracellular water content and has been used to study neuroinflammation across several neurological diseases including AD. Recently, the role of gut microbiota has been implicated in the pathogenesis of AD. The relationship between FW imaging and gut microbiota was examined in patients with AD and MCI. Fifty-six participants underwent neuropsychological assessments, FW imaging, and gut microbiota analysis targeting the bacterial 16S rRNA gene. They were categorized into the cognitively normal control (NC) (n = 19), MCI (n = 19), and AD (n = 18) groups according to the neuropsychological assessments. The correlations of FW values, neuropsychological assessment scores, and the relative abundance of gut microbiota were analyzed. FW was higher in several white matter tracts and in gray matter regions, predominantly the frontal, temporal, limbic and paralimbic regions in the AD/MCI group than in the NC group. In the AD/MCI group, higher FW values in the temporal (superior temporal and temporal pole), limbic and paralimbic (insula, hippocampus and amygdala) regions were the most associated with worse neuropsychological assessment scores. In the AD/MCI group, FW values in these regions were negatively correlated with the relative abundances of butyrate-producing genera Anaerostipes, Lachnospiraceae UCG-004, and [Ruminococcus] gnavus group, which showed a significant decreasing trend in the order of the NC, MCI, and AD groups. The present study showed that increased FW in the gray matter regions related to cognitive impairment was associated with low abundances of butyrate producers in the AD/MCI group. These findings suggest an association between neuroinflammation and decreased levels of the short-chain fatty acid butyrate that is one of the major gut microbial metabolites having a potentially beneficial role in brain homeostasis.
MeSH term(s)	Humans ; Gray Matter/pathology ; Alzheimer Disease/pathology ; Gastrointestinal Microbiome ; Butyrates ; Neuroinflammatory Diseases ; RNA, Ribosomal, 16S ; Cognitive Dysfunction/pathology ; Magnetic Resonance Imaging
Chemical Substances	Butyrates ; RNA, Ribosomal, 16S
Language	English
Publishing date	2024-03-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1211786-9
ISSN	1095-953X ; 0969-9961
ISSN (online)	1095-953X
ISSN	0969-9961
DOI	10.1016/j.nbd.2024.106464
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Article ; Online: Impact of D-dimer for pathologic differentiation on transesophageal echocardiography in embolic stroke of undetermined source: a single-center experience.

Hira, Kenichiro / Ueno, Yuji / Watanabe, Masao / Shimura, Hideki / Kurita, Naohide / Miyamoto, Nobukazu / Haginiwa, Haruna / Yamashiro, Kazuo / Hattori, Nobutaka / Urabe, Takao

BMC neurology

2022 Volume 22, Issue 1, Page(s) 338

Abstract: Background: Embolic stroke of undetermined source (ESUS) encompasses diverse embologenic mechanisms, which transesophageal echocardiography (TEE) is critical to detect. Specific markers related to each embolic source in ESUS is not fully studied. We ... ...

Abstract	Background: Embolic stroke of undetermined source (ESUS) encompasses diverse embologenic mechanisms, which transesophageal echocardiography (TEE) is critical to detect. Specific markers related to each embolic source in ESUS is not fully studied. We focused on D-dimer levels, and explored the association of D-dimer with potential embolic sources (PES) identified on TEE in ESUS. Methods: Consecutive patients with ESUS were included in this study. Clinical characteristics including D-dimer levels were compared between ESUS patients with and without TEE, and among none of, one, and at least two PES in ESUS patients undergoing TEE. Factors related to elevation of D-dimer were analyzed. Results: A total of 211 patients (age, 69.3 ± 13.2 years; 149 males) with ESUS were enrolled. Of these, 115 received TEE, displaying significantly younger age and lower D-dimer levels than patients without TEE (P < 0.05), and 20 (17%), 61 (53%), and 34 (30%) patients were classified into none of, one, and ≥ two PES, respectively. On multiple logistic regression analysis, D-dimer levels were related to one PES (odds ratio [OR]: 9.01; 95% confidence interval [CI]: 1.00-81.51; P = 0.050) and PES ≥ two (OR: 9.76; 95% CI: 1.07-88.97; P = 0.043). Right-to-left shunt (RLS) with deep venous thrombosis (DVT)(OR: 13.94; 95% CI: 1.77-109.99; P = 0.012) and without DVT (OR: 3.90; 95% CI: 1.20-12.70; P = 0.024) were associated with elevation of D-dimer. Conclusions: D-dimer levels were higher in patients with PES. Among PES, RLS, with and without DVT, were associated with increase of D-dimer in ESUS.
MeSH term(s)	Aged ; Aged, 80 and over ; Echocardiography, Transesophageal ; Embolic Stroke ; Embolism/diagnosis ; Fibrin Fibrinogen Degradation Products ; Humans ; Intracranial Embolism/diagnostic imaging ; Male ; Middle Aged ; Risk Factors ; Stroke/diagnostic imaging
Chemical Substances	Fibrin Fibrinogen Degradation Products ; fibrin fragment D
Language	English
Publishing date	2022-09-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2041347-6
ISSN	1471-2377 ; 1471-2377
ISSN (online)	1471-2377
ISSN	1471-2377
DOI	10.1186/s12883-022-02867-z
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Article ; Online: Omega-3 Polyunsaturated Fatty Acids and Stroke Burden.

Ueno, Yuji / Miyamoto, Nobukazu / Yamashiro, Kazuo / Tanaka, Ryota / Hattori, Nobutaka

International journal of molecular sciences

2019 Volume 20, Issue 22

Abstract: Stroke is a major leading cause of death and disability worldwide. N-3 polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid and docosahexaenoic acid have potent anti-inflammatory effects, reduce platelet aggregation, and regress ... ...

Abstract	Stroke is a major leading cause of death and disability worldwide. N-3 polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid and docosahexaenoic acid have potent anti-inflammatory effects, reduce platelet aggregation, and regress atherosclerotic plaques. Since the discovery that the Greenland Eskimo population, whose diet is high in marine n-3 PUFAs, have a lower incidence of coronary heart disease than Western populations, numerous epidemiological studies to explore the associations of dietary intakes of fish and n-3 PUFAs with cardiovascular diseases, and large-scale clinical trials to identify the benefits of treatment with n-3 PUFAs have been conducted. In most of these studies the incidence and mortality of stroke were also evaluated mainly as secondary endpoints. Thus, a systematic literature review regarding the association of dietary intake of n-3 PUFAs with stroke in the epidemiological studies and the treatment effects of n-3 PUFAs in the clinical trials was conducted. Moreover, recent experimental studies were also reviewed to explore the molecular mechanisms of the neuroprotective effects of n-3 PUFAs after stroke.
MeSH term(s)	Cost of Illness ; Fatty Acids, Omega-3/economics ; Fatty Acids, Omega-3/therapeutic use ; Humans ; Incidence ; Stroke/drug therapy ; Stroke/economics ; Stroke/mortality ; United States/epidemiology
Chemical Substances	Fatty Acids, Omega-3
Language	English
Publishing date	2019-11-07
Publishing country	Switzerland
Document type	Journal Article ; Systematic Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms20225549
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Article: Characteristics of Clinical Symptoms, Cerebral Images and Stroke Etiology in Vertebro-Basilar Artery Fenestration-Related Infarction.

Miyamoto, Nobukazu / Ueno, Yuji / Hira, Kenichiro / Kijima, Chikage / Nakajima, Sho / Yamashiro, Kazuo / Hattori, Nobutaka

Brain sciences

2020 Volume 10, Issue 4

Abstract: Cerebral artery fenestration is a rare variant of the vascular architecture, but its existence is well documented. The common site of fenestration is the vertebra-basilar artery and it may be found incidentally with subarachnoid hemorrhage. However, ... ...

Abstract	Cerebral artery fenestration is a rare variant of the vascular architecture, but its existence is well documented. The common site of fenestration is the vertebra-basilar artery and it may be found incidentally with subarachnoid hemorrhage. However, fenestration-related cerebral infarction is rare. We analyzed the clinical characteristics, stroke etiology, and image findings of fenestration-related cerebral infarction of the vertebrobasilar artery. We reviewed our hospital records and previously published reports to find cases of fenestration-related cerebral infarction. We excluded those with unknown clinical features or radiological findings. We retrieved 4 cases of fenestration-related infarction from our hospital, in which vascular change, headache, vertigo/dizziness, and dissection in stroke etiology were detected. In eight previously reported cases of fenestration-related infarction, similar vascular changes were noted, but they were mainly diagnosed as embolic stroke of undetermined source. However, based on the criteria for dissection in this study, dissection as the stroke etiology was suspected in the previously reported cases. Many hypotheses have been proposed for the development of dissection, thrombus, and aneurysms in fenestration. Although an embryological and morphological study is needed, clinicians must consider basilar artery fenestration-related infarction as a differential diagnosis and intensive non-invasive image study is recommended.
Language	English
Publishing date	2020-04-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci10040243
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Article: Stroke classification and treatment support system artificial intelligence for usefulness of stroke diagnosis.

Miyamoto, Nobukazu / Ueno, Yuji / Yamashiro, Kazuo / Hira, Kenichiro / Kijima, Chikage / Kitora, Naoki / Iwao, Yoshihiko / Okuda, Kayo / Mishima, Shohei / Takahashi, Daisuke / Ono, Kazuto / Asari, Mika / Miyazaki, Kazuki / Hattori, Nobutaka

Frontiers in neurology

2023 Volume 14, Page(s) 1295642

Abstract: Background and aims: It is important to diagnose cerebral infarction at an early stage and select an appropriate treatment method. The number of stroke-trained physicians is unevenly distributed; thus, a shortage of specialists is a major problem in ... ...

Abstract	Background and aims: It is important to diagnose cerebral infarction at an early stage and select an appropriate treatment method. The number of stroke-trained physicians is unevenly distributed; thus, a shortage of specialists is a major problem in some regions. In this retrospective design study, we tested whether an artificial intelligence (AI) we built using computer-aided detection/diagnosis may help medical physicians to classify stroke for the appropriate treatment. Methods: To build the Stroke Classification and Treatment Support System AI, the clinical data of 231 hospitalized patients with ischemic stroke from January 2016 to December 2017 were used for training the AI. To verify the diagnostic accuracy, 151 patients who were admitted for stroke between January 2018 and December 2018 were also enrolled. Results: By utilizing multimodal data, such as DWI and ADC map images, as well as patient examination data, we were able to construct an AI that can explain the analysis results with a small amount of training data. Furthermore, the AI was able to classify with high accuracy (Cohort 1, evaluation data 88.7%; Cohort 2, validation data 86.1%). Conclusion: In recent years, the treatment options for cerebral infarction have increased in number and complexity, making it even more important to provide appropriate treatment according to the initial diagnosis. This system could be used for initial treatment to automatically diagnose and classify strokes in hospitals where stroke-trained physicians are not available and improve the prognosis of cerebral infarction.
Language	English
Publishing date	2023-12-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2023.1295642
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Article ; Online: Association between Living Conditions and the Risk Factors, Etiology, and Outcome of Ischemic Stroke in Young Adults.

Kono, Yu / Terasawa, Yuka / Sakai, Kenichiro / Iguchi, Yasuyuki / Nishiyama, Yasuhiro / Nito, Chikako / Suda, Satoshi / Kimura, Kazumi / Murakami, Yoshitaka / Kanzawa, Takao / Yamashiro, Kazuo / Tanaka, Ryota / Okubo, Seiji

Internal medicine (Tokyo, Japan)

2023 Volume 62, Issue 19, Page(s) 2813–2820

Abstract: Objective In recent decades, living conditions have changed drastically. However, there are few data regarding the interaction between living conditions and the risk of ischemic stroke (IS) in young adults. The present study explored the association ... ...

Abstract	Objective In recent decades, living conditions have changed drastically. However, there are few data regarding the interaction between living conditions and the risk of ischemic stroke (IS) in young adults. The present study explored the association between living conditions or marital status and the risk factors, etiology, and outcome of IS in young adults. Methods We prospectively enrolled patients with incident IS who were 20-49 years old from 37 clinical stroke centers. We collected the demographic data, living conditions, marital status, vascular risk factors, disease etiology, treatment, and outcomes at discharge. A comparison group was established using the official statistics of Japan. We categorized patients into the two groups based on living conditions: solitary group and cohabiting group. Clinical characteristics were then compared between living conditions. Results In total, 303 patients were enrolled (224 men; median age at the onset: 44 years old). Significant factors associated with the incidence of IS were as follows: solitary status, body mass index >30 kg/m
MeSH term(s)	Male ; Humans ; Young Adult ; Adult ; Middle Aged ; Ischemic Stroke ; Social Conditions ; Risk Factors ; Stroke/epidemiology ; Stroke/etiology ; Smoking/adverse effects ; Smoking/epidemiology
Language	English
Publishing date	2023-02-22
Publishing country	Japan
Document type	Journal Article
ZDB-ID	32371-8
ISSN	1349-7235 ; 0021-5120 ; 0918-2918
ISSN (online)	1349-7235
ISSN	0021-5120 ; 0918-2918
DOI	10.2169/internalmedicine.0912-22
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