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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: 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: Microbial lipopolysaccharide-induced inflammation contributes to cognitive impairment and white matter lesion progression in diet-induced obese mice with chronic cerebral hypoperfusion.

Inaba, Toshiki / Yamashiro, Kazuo / Kurita, Naohide / Ueno, Yuji / Miyamoto, Nobukazu / Hira, Kenichiro / Nakajima, Sho / Kijima, Chikage / Nakaguro, Ryohei / Urabe, Takao / Hattori, Nobutaka

CNS neuroscience & therapeutics

2023 Volume 29 Suppl 1, Page(s) 200–212

Abstract: Aims: White matter lesions (WMLs) are involved in the pathological processes leading to cognitive decline and dementia. We examined the mechanisms underlying the exacerbation of ischemia-induced cognitive impairment and WMLs by diet-induced obesity, ... ...

Abstract	Aims: White matter lesions (WMLs) are involved in the pathological processes leading to cognitive decline and dementia. We examined the mechanisms underlying the exacerbation of ischemia-induced cognitive impairment and WMLs by diet-induced obesity, including lipopolysaccharide (LPS)-triggered neuroinflammation via toll-like receptor (TLR) 4. Methods: Wild-type (WT) and TLR4-knockout (KO) C57BL/6 mice were fed a high-fat diet (HFD) or low-fat diet (LFD), and subjected to bilateral carotid artery stenosis (BCAS). Diet groups were compared for changes in gut microbiota, intestinal permeability, systemic inflammation, neuroinflammation, WML severity, and cognitive dysfunction. Results: In WT mice, HFD induced obesity and increased cognitive impairment and WML severity compared with LFD-fed mice following BCAS. HFD caused gut dysbiosis and increased intestinal permeability, and plasma LPS and pro-inflammatory cytokine concentrations. Furthermore, HFD-fed mice had higher LPS levels and higher neuroinflammatory status, including increased TLR4 expression, in WMLs. In TLR4-KO mice, HFD also caused obesity and gut dysbiosis but did not increase cognitive impairment or WML severity after BCAS. No difference was found between HFD- and LFD-fed KO mice for LPS levels or inflammatory status in either plasma or WMLs. Conclusion: Inflammation triggered by LPS-TLR4 signaling may mediate obesity-associated exacerbation of cognitive impairment and WMLs from brain ischemia.
MeSH term(s)	Mice ; Animals ; Lipopolysaccharides/toxicity ; Toll-Like Receptor 4/genetics ; Toll-Like Receptor 4/metabolism ; Mice, Obese ; Neuroinflammatory Diseases ; White Matter/pathology ; Dysbiosis ; Mice, Inbred C57BL ; Inflammation/metabolism ; Obesity/complications ; Obesity/metabolism ; Cognitive Dysfunction/pathology ; Brain Ischemia/complications ; Brain Ischemia/pathology ; Diet, High-Fat/adverse effects ; Carotid Stenosis/pathology
Chemical Substances	Lipopolysaccharides ; Toll-Like Receptor 4
Language	English
Publishing date	2023-06-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2423461-8
ISSN	1755-5949 ; 1755-5930
ISSN (online)	1755-5949
ISSN	1755-5930
DOI	10.1111/cns.14301
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Article ; Online: An 88-year-old woman with acute disseminated encephalomyelitis following messenger ribonucleic acid-based COVID-19 vaccination.

Shimizu, Mai / Ogaki, Kotaro / Nakamura, Ryota / Kado, Eriko / Nakajima, Sho / Kurita, Naohide / Watanabe, Masao / Yamashiro, Kazuo / Hattori, Nobutaka / Urabe, Takao

eNeurologicalSci

2021 Volume 25, Page(s) 100381

Abstract: A global pandemic has resulted from the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). To control the spread of SARS-CoV-2 infection, several SARS-CoV-2 vaccines have ...

Abstract	A global pandemic has resulted from the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). To control the spread of SARS-CoV-2 infection, several SARS-CoV-2 vaccines have been developed and administered in a wide range of age groups. Messenger ribonucleic acid (mRNA)-based COVID-19 vaccines are the most widely used. We present the case of an 88-year-old woman who was diagnosed with acute disseminated encephalomyelitis (ADEM) following her second mRNA COVID-19 vaccination. She was admitted to hospital with disturbed consciousness (Glasgow Coma Scale E1V1M4) and gaze-evoked nystagmus. Brain magnetic resonance imaging revealed bilateral presence of middle cerebellar peduncle sign. Following steroid pulse therapy, clinical symptoms improved. The occurrence of ADEM following COVID-19 vaccination does not question the importance of vaccination programs during the COVID-19 pandemic. COVID-19 vaccines have been administered to individuals of a wide range of ages, from children to older adults. Thus, ADEM could occur following COVID-19 vaccination at any age, although ADEM is rare in older adults.
Language	English
Publishing date	2021-11-20
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2838045-9
ISSN	2405-6502 ; 2405-6502
ISSN (online)	2405-6502
ISSN	2405-6502
DOI	10.1016/j.ensci.2021.100381
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Article ; Online: Hashimoto's encephalopathy with gait disturbance caused by sensory ganglionopathy: A case report and review of the literature.

Shimada, Tomoyo / Nakajima, Sho / Nakamura, Ryota / Kurita, Naohide / Ogaki, Kotaro / Watanabe, Masao / Yamashiro, Kazuo / Urabe, Takao

eNeurologicalSci

2021 Volume 25, Page(s) 100370

Abstract: Hashimoto's encephalopathy (HE) is a steroid-responsive encephalopathy characterized by several neurological symptoms. HE mainly involves the central nervous system; the peripheral nervous system is rarely involved. We treated a previously healthy ... ...

Abstract	Hashimoto's encephalopathy (HE) is a steroid-responsive encephalopathy characterized by several neurological symptoms. HE mainly involves the central nervous system; the peripheral nervous system is rarely involved. We treated a previously healthy elderly man showing mild cognitive decline and subacute progressive gait disturbance due to severe sensory deficits, including sensation of touch and deep sensation with elevated anti-NH2 terminal of α-enolase and anti-thyroid antibodies. His sensory disturbance symptoms improved after steroid therapy, suggesting that the neuropathy was related to HE. His disease was characteristic of HE in that his sensory deficits responded well and rapidly to steroid therapy. A nerve conduction study showed reduced sensory nerve action potentials in all limbs, indicating that his neuropathy was not "axonopathy", but "sensory ganglionopathy", which can occur concurrently with autoimmune disorders. Dysautonomia may be the responsible pathomechanism because of the vulnerability of the blood-nerve barrier at the ganglia. Although the pathophysiology of HE has not been clearly elucidated, autoimmune inflammation has been reported in a number of autopsy cases, indicating that sensory ganglionopathy can develop with HE. Therefore, HE should be recognized as one type of "treatable neuropathy".
Language	English
Publishing date	2021-10-02
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2838045-9
ISSN	2405-6502 ; 2405-6502
ISSN (online)	2405-6502
ISSN	2405-6502
DOI	10.1016/j.ensci.2021.100370
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Article: Post-Treatment Plasma D-Dimer Levels Are Associated With Short-Term Outcomes in Patients With Cancer-Associated Stroke.

Nakajima, Sho / Kawano, Hiroyuki / Yamashiro, Kazuo / Tanaka, Ryota / Kameda, Tomoaki / Kurita, Naohide / Hira, Kenichiro / Miyamoto, Nobukazu / Ueno, Yuji / Watanabe, Masao / Hirano, Teruyuki / Fujimoto, Shigeru / Urabe, Takao / Hattori, Nobutaka

Frontiers in neurology

2022 Volume 13, Page(s) 868137

Abstract: Background and objective: Hypercoagulability is associated with increased risks of ischemic stroke and subsequent mortality in patients with active cancer. This study investigated the relationships between plasma D-dimer levels after stroke treatment ... ...

Abstract	Background and objective: Hypercoagulability is associated with increased risks of ischemic stroke and subsequent mortality in patients with active cancer. This study investigated the relationships between plasma D-dimer levels after stroke treatment and short-term outcomes in patients with cancer-associated stroke. Methods: This retrospective, observational, multicenter study analyzed consecutive patients with cancer-associated ischemic stroke. Hypercoagulability was assessed by plasma D-dimer levels before and after stroke treatment. Short-term outcomes were assessed in terms of poor outcomes (a modified Rankin Scale score >3), cumulative rates of recurrent ischemic stroke, and mortality at 30 days after admission. Results: Of 282 patients, 135 (47.9%) showed poor outcomes. Recurrent ischemic stroke was observed in 28 patients (9.9%), and the cumulative mortality rate was 12.4%. Multivariate analysis showed that post-treatment plasma D-dimer levels ≥10 μg/ml were independently associated with both poor outcomes (adjusted odds ratio [OR], 9.61; 95% confidence interval [CI], 3.60-25.70; Conclusion: A high plasma D-dimer level after stroke treatment was associated with poor short-term outcomes in patients with cancer-associated stroke. Using anticoagulants to reduce D-dimer levels may improve short-term outcomes in these patients.
Language	English
Publishing date	2022-04-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2022.868137
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Article ; Online: Teaching Video NeuroImages: Re-emergent jaw tremor in Parkinson disease.

Hatano, Taku / Kurita, Naohide / Kobayashi, Manami / Hattori, Nobutaka

Neurology

2015 Volume 85, Issue 23, Page(s) e181

MeSH term(s)	Aged ; Female ; Humans ; Jaw/pathology ; Parkinson Disease/complications ; Parkinson Disease/diagnosis ; Recurrence ; Tremor/diagnosis ; Tremor/etiology
Language	English
Publishing date	2015-12-08
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000002189
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Article ; Online: Eicosapentaenoic-to-Arachidonic Acid Ratio Predicts Mortality and Recurrent Vascular Events in Ischemic Stroke Patients.

Shojima, Yuri / Ueno, Yuji / Tanaka, Ryota / Yamashiro, Kazuo / Miyamoto, Nobukazu / Hira, Kenichiro / Kurita, Naohide / Nakajima, Sho / Urabe, Takao / Hattori, Nobutaka

Journal of atherosclerosis and thrombosis

2020 Volume 27, Issue 9, Page(s) 969–977

Abstract: Aims: The ratio of eicosapentaenoic acid (EPA) to arachidonic acid (AA) is related to major adverse events and death in cardiovascular diseases. The association between long-term prognosis of ischemic stroke and EPA/AA ratio has not been clarified.: ... ...

Abstract	Aims: The ratio of eicosapentaenoic acid (EPA) to arachidonic acid (AA) is related to major adverse events and death in cardiovascular diseases. The association between long-term prognosis of ischemic stroke and EPA/AA ratio has not been clarified. Methods: Acute ischemic stroke patients who had undergone blood examinations for polyunsaturated fatty acids were enrolled. Major cardiovascular events, including recurrence of ischemic stroke, occurrence of cardiovascular and peripheral artery diseases and hemorrhagic stroke, and death, were analyzed, retrospectively. Cox proportional hazards regression analysis was used to explore factors, including clinical characteristics, laboratory data including EPA/AA ratio, and treatments associated with major cardiovascular events and death. Results: A total of 269 patients (mean age, 70±13 years; 179 men) were enrolled. During follow-up (mean, 2.3 ±1.0 years), 64 patients exhibited major cardiovascular events and death (annualized rate, 10.5% per person-year). Multivariate Cox analysis revealed that EPA/AA ratio (hazard ratio, 0.26; 95% confidence interval, 0.07- 0.99; p=0.048) and statin therapy (hazard ratio, 0.43; 95% confidence interval, 0.25-0.73; p=0.002) correlated inversely with major cardiovascular events and death. In the Kaplan-Meier analysis, cumulative event-free rates were significantly lower among patients with EPA/AA ratio ＜0.33 and patients without statin therapy (p=0.006). Conclusions: Low EPA/AA ratio at baseline and treatment without statins could predict mortality, recurrent ischemic stroke, cardiovascular and peripheral artery diseases, and hemorrhagic stroke among patients with acute ischemic stroke. The combination of baseline EPA/AA ratio and statin therapy could be critical in predicting the long-term prognosis of ischemic stroke patients.
Language	English
Publishing date	2020-01-23
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2011474-6
ISSN	1880-3873 ; 1340-3478
ISSN (online)	1880-3873
ISSN	1340-3478
DOI	10.5551/jat.52373
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Article ; Online: Cerebral Microbleeds and Chronic Kidney Disease in Acute Ischemic Stroke Patients with Atrial Fibrillation.

Yamashiro, Kazuo / Tanaka, Ryota / Kurita, Naohide / Ueno, Yuji / Miyamoto, Nobukazu / Hira, Kenichiro / Nakajima, Sho / Urabe, Takao / Hattori, Nobutaka

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

2020 Volume 29, Issue 4, Page(s) 104650

Abstract: Background: Cerebral microbleeds (CMBs) are associated with the risk of intracerebral hemorrhage in stroke patients with atrial fibrillation (AF). We investigated the association between CMBs and chronic kidney disease (CKD) in patients with acute ... ...

Abstract	Background: Cerebral microbleeds (CMBs) are associated with the risk of intracerebral hemorrhage in stroke patients with atrial fibrillation (AF). We investigated the association between CMBs and chronic kidney disease (CKD) in patients with acute ischemic stroke and AF. Methods: We retrospectively examined consecutive patients with acute ischemic stroke and AF who underwent brain gradient-echo T2-weighted magnetic resonance imaging. The number and distribution (lobar, deep or infratentorial, and mixed) of CMBs were assessed. Kidney function was assessed according to the estimated glomerular filtration rate (eGFR), which was calculated using a modified version of the Modification of Diet in Renal Disease equation. Results:* Of the 357 included patients, 105 (29.4%) had CMBs. CKD (eGFR < 60 mL/min/1.73 m Conclusions: CMBs and CKD are common in acute ischemic stroke patients with AF, and CKD may be a risk factor for CMBs. Further longitudinal studies are needed to evaluate whether maintaining kidney function can prevent the development of CMBs.
MeSH term(s)	Aged ; Atrial Fibrillation/diagnosis ; Atrial Fibrillation/epidemiology ; Atrial Fibrillation/physiopathology ; Brain Ischemia/diagnostic imaging ; Brain Ischemia/epidemiology ; Brain Ischemia/physiopathology ; Cerebral Hemorrhage/diagnostic imaging ; Cerebral Hemorrhage/epidemiology ; Cerebral Hemorrhage/physiopathology ; Female ; Glomerular Filtration Rate ; Humans ; Japan/epidemiology ; Kidney/physiopathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic/diagnosis ; Renal Insufficiency, Chronic/epidemiology ; Renal Insufficiency, Chronic/physiopathology ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Severity of Illness Index ; Stroke/diagnostic imaging ; Stroke/epidemiology ; Stroke/physiopathology
Language	English
Publishing date	2020-02-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	1131675-5
ISSN	1532-8511 ; 1052-3057
ISSN (online)	1532-8511
ISSN	1052-3057
DOI	10.1016/j.jstrokecerebrovasdis.2020.104650
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Article ; Online: Mucosal-Associated Invariant T Cells Are Involved in Acute Ischemic Stroke by Regulating Neuroinflammation.

Nakajima, Sho / Tanaka, Ryota / Yamashiro, Kazuo / Chiba, Asako / Noto, Daisuke / Inaba, Toshiki / Kurita, Naohide / Miyamoto, Nobukazu / Kuroki, Takuma / Shimura, Hideki / Ueno, Yuji / Urabe, Takao / Miyake, Sachiko / Hattori, Nobutaka

Journal of the American Heart Association

2021 Volume 10, Issue 7, Page(s) e018803

Abstract: Background Mucosal-associated invariant T (MAIT) cells have been associated with inflammation in several autoimmune diseases. However, their relation to ischemic stroke remains unclear. This study attempted to elucidate the role of MAIT cells in acute ... ...

Abstract	Background Mucosal-associated invariant T (MAIT) cells have been associated with inflammation in several autoimmune diseases. However, their relation to ischemic stroke remains unclear. This study attempted to elucidate the role of MAIT cells in acute ischemic stroke in mice. Methods and Results We used MR1 knockout C57BL/6 (MR1
MeSH term(s)	Acute Disease ; Animals ; Disease Models, Animal ; Immunity, Cellular ; Inflammation/immunology ; Ischemic Stroke/immunology ; Ischemic Stroke/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Mucosal-Associated Invariant T Cells/immunology ; Mice
Language	English
Publishing date	2021-03-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.120.018803
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