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Article ; Online: New Alzheimer’s disease model mouse specialized for analyzing the function and toxicity of intraneuronal Amyloid β oligomers

Tomoyo Ochiishi / Masami Kaku / Kazuyuki Kiyosue / Motomichi Doi / Takao Urabe / Nobutaka Hattori / Hideki Shimura / Tatsuhiko Ebihara

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 15

Abstract: Abstract Oligomers of intracellular amyloid β protein (Aβ) are strongly cytotoxic and play crucial roles in synaptic transmission and cognitive function in Alzheimer’s disease (AD). However, there is currently no AD model mouse in which to specifically ... ...

Abstract	Abstract Oligomers of intracellular amyloid β protein (Aβ) are strongly cytotoxic and play crucial roles in synaptic transmission and cognitive function in Alzheimer’s disease (AD). However, there is currently no AD model mouse in which to specifically analyze the function of Aβ oligomers only. We have now developed a novel AD model mouse, an Aβ-GFP transgenic mouse (Aβ-GFP Tg), that expresses the GFP-fused human Aβ1-42 protein, which forms only Aβ oligomers within neurons throughout their life. The fusion proteins are expressed mainly in the hippocampal CA1-CA2 region and cerebral cortex, and are not secreted extracellularly. The Aβ-GFP Tg mice exhibit increased tau phosphorylation, altered spine morphology, decreased expressions of the GluN2B receptor and neuroligin in synaptic regions, attenuated hippocampal long-term potentiation, and impaired object recognition memory compared with non-Tg littermates. Interestingly, these dysfunctions have already appeared in 2–3-months-old animals. The Aβ-GFP fusion protein is bioactive and highly toxic, and induces the similar synaptic dysfunctions as the naturally generated Aβ oligomer derived from postmortem AD patient brains and synthetic Aβ oligomers. Thus, Aβ-GFP Tg mouse is a new tool specialized to analyze the function of Aβ oligomers in vivo and to find subtle changes in synapses in early symptoms of AD.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2019-11-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Phosphorylated recombinant HSP27 protects the brain and attenuates blood-brain barrier disruption following stroke in mice receiving intravenous tissue-plasminogen activator.

Yoshiaki Shimada / Hideki Shimura / Ryota Tanaka / Kazuo Yamashiro / Masato Koike / Yasuo Uchiyama / Takao Urabe / Nobutaka Hattori

PLoS ONE, Vol 13, Iss 5, p e

2018 Volume 0198039

Abstract: Loss of integrity of the blood-brain barrier (BBB) in ischemic stroke victims initiates a devastating cascade of events causing brain damage. Maintaining the BBB is important to preserve brain function in ischemic stroke. Unfortunately, recombinant ... ...

Abstract	Loss of integrity of the blood-brain barrier (BBB) in ischemic stroke victims initiates a devastating cascade of events causing brain damage. Maintaining the BBB is important to preserve brain function in ischemic stroke. Unfortunately, recombinant tissue plasminogen activator (tPA), the only effective fibrinolytic treatment at the acute stage of ischemic stroke, also injures the BBB and increases the risk of brain edema and secondary hemorrhagic transformation. Thus, it is important to identify compounds that maintain BBB integrity in the face of ischemic injury in patients with stroke. We previously demonstrated that intravenously injected phosphorylated recombinant heat shock protein 27 (prHSP27) protects the brains of mice with transient middle cerebral artery occlusion (tMCAO), an animal stroke-model. Here, we determined whether prHSP27, in addition to attenuating brain injury, also decreases BBB damage in hyperglycemic tMCAO mice that had received tPA. After induction of hyperglycemia and tMCAO, we examined 4 treatment groups: 1) bovine serum albumin (BSA), 2) prHSP27, 3) tPA, 4) tPA plus prHSP27. We examined the effects of prHSP27 by comparing the BSA and prHSP27 groups and the tPA and tPA plus prHSP27 groups. Twenty-four hours after injection, prHSP27 reduced infarct volume, brain swelling, neurological deficits, the loss of microvessel proteins and endothelial cell walls, and mortality. It also reduced the rates of hemorrhagic transformation, extravasation of endogenous IgG, and MMP-9 activity, signs of BBB damage. Therefore, prHSP27 injection attenuated brain damage and preserved the BBB in tPA-injected, hyperglycemic tMCAO experimental stroke-model mice, in which the BBB is even more severely damaged than in simple tMCAO mice. The attenuation of brain damage and BBB disruption in the presence of tPA suggests the effectiveness of prHSP27 and tPA as a combination therapy. prHSP27 may be a novel therapeutic agent for ischemic stroke patients whose BBBs are injured following tPA injections.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Different aspects of early and late development of atrial fibrillation during hospitalization in cryptogenic stroke

Ryosuke Doijiri / Yuji Ueno / Muneaki Kikuno / Takahiro Shimizu / Yohei Tateishi / Ayako Kuriki / Hidehiro Takekawa / Yoshiaki Shimada / Kodai Kanemaru / Yuki Kamiya / Eriko Yamaguchi / Masatoshi Koga / Masafumi Ihara / Akira Tsujino / Koichi Hirata / Yasuhiro Hasegawa / Takahiko Kikuchi / Nobutaka Hattori / Takao Urabe

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 7

Abstract: Abstract The detection of underlying atrial fibrillation (AF) has become increasingly possible by insertable cardiac monitoring (ICM). During hospitalization for cryptogenic stroke, factors related to the early and late development of AF have not been ... ...

Abstract	Abstract The detection of underlying atrial fibrillation (AF) has become increasingly possible by insertable cardiac monitoring (ICM). During hospitalization for cryptogenic stroke, factors related to the early and late development of AF have not been studied. CHALLENGE ESUS/CS is a multicenter registry of cryptogenic stroke patients undergoing transesophageal echocardiography. Twelve-lead electrocardiogram, continuous cardiac monitoring, and 24-h Holter electrocardiogram were all used for the detection of AF. Early and late detection of AF was determined with an allocation ratio of 1:1 among patients with AF. A total of 677 patients (68.7 ± 12.8 years; 455 men) were enrolled, and 64 patients developed AF during hospitalization. Four days after admission was identified as the approximate median day to classify early and late phases to detect AF: ≤ 4 days, 37 patients; > 4 days, 27 patients. Multiple logistic regression analysis showed that spontaneous echo contrast (SEC) (OR 5.91; 95% CI 2.19–15.97; p < 0.001) was associated with AF ≤ 4 days, whereas a large infarction > 3 cm in diameter (OR 3.28; 95% CI 1.35–7.97; p = 0.009) was associated with AF > 4 days. SEC and large infarctions were important predictors of in-hospital AF detection, particularly in the early and late stages, respectively; thus, they could serve as indications for recommending ICM.
Keywords	Medicine ; R ; Science ; Q
Subject code	616 ; 610
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Correction

Kazuo Yamashiro / Ryota Tanaka / Takao Urabe / Yuji Ueno / Yuichiro Yamashiro / Koji Nomoto / Takuya Takahashi / Hirokazu Tsuji / Takashi Asahara / Nobutaka Hattori

PLoS ONE, Vol 12, Iss 4, p e

Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke.

2017 Volume 0176062

Abstract: This corrects the article DOI:10.1371/journal.pone.0171521.]. ...

Abstract	[This corrects the article DOI:10.1371/journal.pone.0171521.].
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke.

Kazuo Yamashiro / Ryota Tanaka / Takao Urabe / Yuji Ueno / Yuichiro Yamashiro / Koji Nomoto / Takuya Takahashi / Hirokazu Tsuji / Takashi Asahara / Nobutaka Hattori

PLoS ONE, Vol 12, Iss 2, p e

2017 Volume 0171521

Abstract: The role of metabolic diseases in ischemic stroke has become a primary concern in both research and clinical practice. Increasing evidence suggests that dysbiosis is associated with metabolic diseases. The aim of this study was to investigate whether the ...

Abstract	The role of metabolic diseases in ischemic stroke has become a primary concern in both research and clinical practice. Increasing evidence suggests that dysbiosis is associated with metabolic diseases. The aim of this study was to investigate whether the gut microbiota, as well as concentrations of organic acids, the major products of dietary fiber fermentation by the gut microbiota, are altered in patients with ischemic stroke, and to examine the association between these changes and host metabolism and inflammation. We analyzed the composition of the fecal gut microbiota and the concentrations of fecal organic acids in 41 ischemic stroke patients and 40 control subjects via 16S and 23S rRNA-targeted quantitative reverse transcription (qRT)-PCR and high-performance liquid chromatography analyses, respectively. Multivariable linear regression analysis was subsequently performed to evaluate the relationships between ischemic stroke and bacterial counts and organic acid concentrations. Correlations between bioclinical markers and bacterial counts and organic acids concentrations were also evaluated. Although only the bacterial counts of Lactobacillus ruminis were significantly higher in stroke patients compared to controls, multivariable analysis showed that ischemic stroke was independently associated with increased bacterial counts of Atopobium cluster and Lactobacillus ruminis, and decreased numbers of Lactobacillus sakei subgroup, independent of age, hypertension, and type 2 diabetes. Changes in the prevalence of Lactobacillus ruminis were positively correlated with serum interleukin-6 levels. In addition, ischemic stroke was associated with decreased and increased concentrations of acetic acid and valeric acid, respectively. Meanwhile, changes in acetic acid concentrations were negatively correlated with the levels of glycated hemoglobin and low-density lipoprotein cholesterol, whereas changes in valeric acid concentrations were positively correlated with the level of high sensitivity C-reactive protein and ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Randomised placebo-controlled multicentre trial to evaluate the efficacy and safety of JTR-161, allogeneic human dental pulp stem cells, in patients with Acute Ischaemic stRoke (J-REPAIR)

Hideo Hara / Nobuyuki Sakai / Shinichi Yoshimura / Masafumi Ihara / Satoshi Suda / Chikako Nito / Kazumi Kimura / Yuji Matsumaru / Taketo Hatano / Masaki Takao / Takeshi Yoshimoto / Masahiro Yasaka / Masafumi Morimoto / Akira Tsujino / Takeshi Inoue / Seiji Okubo / Mitsuyasu Kanai / Kenichi Morita / Yuka Terasawa /

Yasuyuki Iguchi / Takao Urabe / Masataka Takeuchi / Shinichi Takahashi / Yasuhisa Akaiwa / Norihiro Ishii / Takao Kanzawa / Eiichiro Kamatsuka / Takeshi Iwanaga / Ryuzaburo Kanazawa / Norimichi Nakamura / Yutaka Honma / Tomohiko Izumidani / Shoji Arihiro / Takayuki Mizunari

BMJ Open, Vol 12, Iss

2022 Volume 5

Keywords	Medicine ; R
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Resection of Multiple Neurinomas of the Cauda Equina Improves Normal Pressure Hydrocephalus

Atsuhito Fuse / Kenya Nishioka / Hideki Shimura / Wataru Manabe / Ryota Tanaka / Nobutaka Hattori / Takao Urabe

Open Journal of Modern Neurosurgery , Vol 02, Iss 03, Pp 54-

2012 Volume 57

Abstract: Normal pressure hydrocephalus (NPH) is a treatable neurological condition characterized by dementia, gait disturbances, and urinary incontinence. This case study aimed to evaluate the effectiveness of surgical intervention in treating NPH associated with ...

Abstract	Normal pressure hydrocephalus (NPH) is a treatable neurological condition characterized by dementia, gait disturbances, and urinary incontinence. This case study aimed to evaluate the effectiveness of surgical intervention in treating NPH associated with spinal cord tumors. A patient suffering with NPH underwent a spinal tap procedure and surgical resectioning of three neurinomas on the cauda equina. The patient exhibited marked improvement in neurological and motor symptoms related to NPH following surgical intervention. These findings suggest that surgical resectioning of neurinomas is an effective intervention for treating NPH associated with spinal cord tumors.
Keywords	Normal Pressure Hydrocephalus ; Spinal Cord Tumor ; Dementia ; Neurinoma ; Surgery ; RD1-811 ; Medicine ; R ; DOAJ:Surgery ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Language	English
Publishing date	2012-07-01T00:00:00Z
Publisher	Scientific Research Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Endothelial cell proliferation in swine experimental aneurysm after coil embolization.

Yumiko Mitome-Mishima / Munetaka Yamamoto / Kenji Yatomi / Senshu Nonaka / Nobukazu Miyamoto / Takao Urabe / Hajime Arai / Hidenori Oishi

PLoS ONE, Vol 9, Iss 2, p e

2014 Volume 89047

Abstract: After coil embolization, recanalization in cerebral aneurysms adversely influences long-term prognosis. Proliferation of endothelial cells on the coil surface may reduce the incidence of recanalization and further improve outcomes after coil embolization. ...

Abstract	After coil embolization, recanalization in cerebral aneurysms adversely influences long-term prognosis. Proliferation of endothelial cells on the coil surface may reduce the incidence of recanalization and further improve outcomes after coil embolization. We aimed to map the expression of proliferating tissue over the aneurysmal orifice and define the temporal profile of tissue growth in a swine experimental aneurysm model. We compared the outcomes after spontaneous thrombosis with those of coil embolization using histological and morphological techniques. In aneurysms that we not coiled, spontaneous thrombosis was observed, and weak, easily detachable proliferating tissue was evident in the aneurysmal neck. In contrast, in the coil embolization group, histological analysis showed endothelial-like cells lining the aneurysmal opening. Moreover, immunohistochemical and morphological analysis suggested that these cells were immature endothelial cells. Our results indicated the existence of endothelial cell proliferation 1 week after coil embolization and showed immature endothelial cells in septal tissue between the systemic circulation and the aneurysm. These findings suggest that endothelial cells are lead to and proliferate in the former aneurysmal orifice. This is the first examination to evaluate the temporal change of proliferating tissue in a swine experimental aneurysm model.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Adrenomedullin Deficiency and Aging Exacerbate Ischemic White Matter Injury after Prolonged Cerebral Hypoperfusion in Mice

Yumiko Mitome-Mishima / Nobukazu Miyamoto / Ryota Tanaka / Tatsuo Shimosawa / Hidenori Oishi / Hajime Arai / Nobutaka Hattori / Takao Urabe

BioMed Research International, Vol

2014 Volume 2014

Abstract: Adrenomedullin was originally isolated from pheochromocytoma cells and reduces insulin resistance by decreasing oxidative stress. White matter lesions induced by aging and hyperglycemia play a crucial role in cognitive impairment in poststroke patients. ... ...

Abstract	Adrenomedullin was originally isolated from pheochromocytoma cells and reduces insulin resistance by decreasing oxidative stress. White matter lesions induced by aging and hyperglycemia play a crucial role in cognitive impairment in poststroke patients. Here, we examine whether adrenomedullin deficiency and aging exacerbate ischemic white matter injury after prolonged cerebral hypoperfusion. Adrenomedullin heterozygous, wild-type young/aged mice were subjected to prolonged hypoperfusion. Prolonged cerebral hypoperfusion followed by immunohistochemical analysis was used to evaluate white matter injury. After prolonged hypoperfusion, white matter damage progressed in a time-dependent manner in AM+/− group compared with the wild-type group. The number of oligodendrocyte progenitor cells gradually increased after prolonged hypoperfusion, whereas oligodendrocytes decreased following a transient increase, but the ratio of increase was mild in the AM+/− group (P<0.05). Oxidative stress was detected in oligodendrocytes, with a larger increase in the AM+/− group (P<0.05). Aged mice showed the same tendency, but white matter damage was worse, especially in the aged AM+/− group. Our results demonstrated that white matter injury was increased in adrenomedullin deficiency, which induced oxidative stress. White matter injury was more exacerbated because of hyperglycemia in aged AM+/− group. Adrenomedullin may be an important target in the control of ischemic white matter injury.
Keywords	Medicine ; R
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cerebral infarction in a young man using high-dose anabolic steroids.

Shimada, Yoshiaki / Yoritaka, Asako / Tanaka, Yasutaka / Miyamoto, Nobukazu / Ueno, Yuji / Hattori, Nobutaka / Takao, Urabe

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

2012 Volume 21, Issue 8, Page(s) 906.e9–11

Abstract: Anabolic androgenic steroid (AAS) abuse has increased among athletes in recent years. However, AAS abuse can increase hypercoagulopathy and cause cerebrovascular disease. We report a case of a 27-year-old man who had right hemiparalysis, hemianopia, ... ...

Abstract	Anabolic androgenic steroid (AAS) abuse has increased among athletes in recent years. However, AAS abuse can increase hypercoagulopathy and cause cerebrovascular disease. We report a case of a 27-year-old man who had right hemiparalysis, hemianopia, dysarthria, and double vision in the middle of muscle training. He suspected acute disseminated encephalomyelitis at first, because of a preceding respiratory infection. However, extensive work-up was performed, including brain magnetic resonance imaging, transcranial Doppler and transesophageal echocardiography, confirming the final diagnosis of cardioembolic stroke. Physicians should be aware that cerebrovascular disease may be a side effect of AAS, even in younger populations.
MeSH term(s)	Adult ; Anabolic Agents/adverse effects ; Androgens/adverse effects ; Cerebral Infarction/chemically induced ; Cerebral Infarction/diagnosis ; Echocardiography, Transesophageal ; Foramen Ovale, Patent/complications ; Foramen Ovale, Patent/diagnosis ; Heart Aneurysm/complications ; Heart Aneurysm/diagnosis ; Humans ; Magnetic Resonance Imaging ; Male ; Predictive Value of Tests ; Risk Factors ; Ultrasonography, Doppler, Transcranial ; Venous Thrombosis/chemically induced
Chemical Substances	Anabolic Agents ; Androgens
Language	English
Publishing date	2012-11
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	1131675-5
ISSN	1532-8511 ; 1052-3057
ISSN (online)	1532-8511
ISSN	1052-3057
DOI	10.1016/j.jstrokecerebrovasdis.2011.07.013
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