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Article ; Online: Association of bleb formation with peri-aneurysmal contact in unruptured intracranial aneurysms

Toru Satoh / Takanobu Yagi / Yoichi Sawada / Kenji Sugiu / Yu Sato / Isao Date

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 8

Abstract: Abstract The mechanism of bleb formation in unruptured intracranial aneurysms (UIAs) remains unclear. This study aimed to investigate the association between peri-aneurysmal contact (PAC) and bleb formation. Forty-five aneurysms were classified depending ...

Abstract	Abstract The mechanism of bleb formation in unruptured intracranial aneurysms (UIAs) remains unclear. This study aimed to investigate the association between peri-aneurysmal contact (PAC) and bleb formation. Forty-five aneurysms were classified depending on the presence of blebs and PAC using computed tomographic angiography and magnetic resonance imaging. Aneurysmal hemodynamics were assessed using computational fluid dynamics. The independent variables associated with bleb formation were statistically assessed. Fourteen aneurysms (31.1%) had blebs, all of which were located at the site of PAC (group A). Thirty-one aneurysms (68.9%) had no bleb, of which 13 had a PAC (group B) and 18 had no PAC (group C). PAC was the only independent variable associated with bleb formation (p < 0.05). Aneurysmal volumes were significantly higher in group A, followed by groups B and C in series. Aneurysmal wall shear stress (WSS) tended to be lowest in group A, followed by groups B and C in series. The maximum WSS at the blebs was only 17% of the maximum WSS at the aneurysmal domes. This study demonstrated that bleb formation in UIAs was associated with the establishment of PAC during their growth, which may have more detrimental effects on bleb formation than hemodynamics.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Animal Models for Parkinson’s Disease Research

Kyohei Kin / Takao Yasuhara / Masahiro Kameda / Isao Date

International Journal of Molecular Sciences, Vol 20, Iss 21, p

Trends in the 2000s

2019 Volume 5402

Abstract: Parkinson’s disease (PD) is a chronic and progressive movement disorder and the second most common neurodegenerative disease. Although many studies have been conducted, there is an unmet clinical need to develop new treatments because, currently, only ... ...

Abstract	Parkinson’s disease (PD) is a chronic and progressive movement disorder and the second most common neurodegenerative disease. Although many studies have been conducted, there is an unmet clinical need to develop new treatments because, currently, only symptomatic therapies are available. To achieve this goal, clarification of the pathology is required. Attempts have been made to emulate human PD and various animal models have been developed over the decades. Neurotoxin models have been commonly used for PD research. Recently, advances in transgenic technology have enabled the development of genetic models that help to identify new approaches in PD research. However, PD animal model trends have not been investigated. Revealing the trends for PD research will be valuable for increasing our understanding of the positive and negative aspects of each model. In this article, we clarified the trends for animal models that were used to research PD in the 2000s, and we discussed each model based on these trends.
Keywords	animal model ; α-synuclein ; dj-1 ; neurotoxin ; parkin ; parkinson’s disease ; pesticide ; pink1 ; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; 6-hydroxydopamine ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	006
Language	English
Publishing date	2019-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Precise MEP monitoring with a reduced interval is safe and useful for detecting permissive duration for temporary clipping

Masahiro Kameda / Tomohito Hishikawa / Masafumi Hiramatsu / Takao Yasuhara / Kazuhiko Kurozumi / Isao Date

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 8

Abstract: Abstract Although temporary clipping of the parent artery is an indispensable technique in clipping surgery for intracranial aneurysms, the permissive duration of temporary clipping is still not well known. The aim of this study is to confirm the safety ... ...

Abstract	Abstract Although temporary clipping of the parent artery is an indispensable technique in clipping surgery for intracranial aneurysms, the permissive duration of temporary clipping is still not well known. The aim of this study is to confirm the safety of precise motor evoked potential (MEP) monitoring and to estimate the permissive duration of temporary clipping for middle cerebral artery (MCA) aneurysm based on precise MEP monitoring results. Under precise MEP monitoring via direct cortical stimulation every 30 seconds to 1 minute, surgeons released a temporary clip and waited for MEP amplitude to recover following severe (>50%) reduction of MEP amplitude during temporary clipping. Precise MEP monitoring was safely performed. Twenty-eight instances of temporary clipping were performed in 42 MCA aneurysm clipping surgeries. Because precise MEP monitoring could be used to determine when to release a temporary clip even with a severe reduction in MEP amplitude due to lengthy temporary clipping, no patients experienced permanent postoperative hemiparesis. Based on logistic regression analysis, if a temporary clip is applied for 312 seconds or more, there is a higher probability of a severe reduction in MEP amplitude. We should therefore release temporary clips after 5 minutes in order to avoid permanent postoperative hemiparesis.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Limiting exercise inhibits neuronal recovery from neurological disorders

Stefan S Anthony / Isao Date / Takao Yasuhara

Brain Circulation, Vol 3, Iss 3, Pp 124-

2017 Volume 129

Abstract: Patients who are bedridden often suffer from muscular atrophy due to reduced daily activities and can become depressed. However, patients who undergo physical therapy sometimes demonstrate positive benefits including a reduction of stressful and ... ...

Abstract	Patients who are bedridden often suffer from muscular atrophy due to reduced daily activities and can become depressed. However, patients who undergo physical therapy sometimes demonstrate positive benefits including a reduction of stressful and depressed behavior. Regenerative medicine has seen improvements in two stem cell-based therapies for central nervous system disorders. One therapy is through the transfer of exogenous stem cells. The other therapy is a more natural method and focuses on the increasing endogenous neurogenesis and restoring the neurological impairments. This study overviews how immobilization-induced disuse atrophy affects neurogenesis in rats, specifically hypothesizing that immobilization diminishes circulating trophic factor levels, like vascular endothelial growth factors or brain-derived neurotrophic factor, which in turn limits neurogenesis. This hypothesis requires the classification of the stem cell microenvironment by probing growth factors in addition to other stress-related proteins that correlate with exercise-induced neurogenesis. There is research examining the effects of increased exercise on neurogenesis while limiting exercise, which better demonstrates the pathological states of immobile stroke patients, remains relatively unexplored. To examine the effects of immobilization on neurogenesis quantitative measurements of movements, 5-bromo-2deoxyuridine labeling of proliferative cells, biochemical assays of serum, cerebrospinal fluid and neurological levels of trophic factors, growth factors, and stress-related proteins will indicate levels of neurogenesis. In further research, studies are needed to show how in vivo stimulation, or lack thereof, affects stem cell microenvironments to advance treatment procedures for strengthening neurogenesis in bedridden patients. This paper is a review article. Referred literature in this paper has been listed in the references section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.
Keywords	central nervous system disorders ; exercise ; muscular atrophy ; neurogenesis ; regenerative medicine ; stem-cell therapy ; Medical technology ; R855-855.5 ; Diseases of the circulatory (Cardiovascular) system ; RC666-701
Subject code	610
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Wolters Kluwer Medknow Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic stroke

Satoru Yabuno / Takao Yasuhara / Takayuki Nagase / Satoshi Kawauchi / Chiaki Sugahara / Yosuke Okazaki / Kakeru Hosomoto / Susumu Sasada / Tatsuya Sasaki / Naoki Tajiri / Cesar V. Borlongan / Isao Date

Stem Cell Research & Therapy, Vol 14, Iss 1, Pp 1-

2023 Volume 19

Abstract: Abstract Background Mesenchymal stromal cell (MSC) transplantation therapy is a promising therapy for stroke patients. In parallel, rehabilitation with physical exercise could ameliorate stroke-induced neurological impairment. In this study, we aimed to ... ...

Abstract	Abstract Background Mesenchymal stromal cell (MSC) transplantation therapy is a promising therapy for stroke patients. In parallel, rehabilitation with physical exercise could ameliorate stroke-induced neurological impairment. In this study, we aimed to clarify whether combination therapy of intracerebral transplantation of human modified bone marrow-derived MSCs, SB623 cells, and voluntary exercise with running wheel (RW) could exert synergistic therapeutic effects on a rat model of ischemic stroke. Methods Wistar rats received right transient middle cerebral artery occlusion (MCAO). Voluntary exercise (Ex) groups were trained in a cage with RW from day 7 before MCAO. SB623 cells (4.0 × 105 cells/5 μl) were stereotactically injected into the right striatum at day 1 after MCAO. Behavioral tests were performed at day 1, 7, and 14 after MCAO using the modified Neurological Severity Score (mNSS) and cylinder test. Rats were euthanized at day 15 after MCAO for mRNA level evaluation of ischemic infarct area, endogenous neurogenesis, angiogenesis, and expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). The rats were randomly assigned to one of the four groups: vehicle, Ex, SB623, and SB623 + Ex groups. Results SB623 + Ex group achieved significant neurological recovery in mNSS compared to the vehicle group (p < 0.05). The cerebral infarct area of SB623 + Ex group was significantly decreased compared to those in all other groups (p < 0.05). The number of BrdU/Doublecortin (Dcx) double-positive cells in the subventricular zone (SVZ) and the dentate gyrus (DG), the laminin-positive area in the ischemic boundary zone (IBZ), and the mRNA level of BDNF and VEGF in SB623 + Ex group were significantly increased compared to those in all other groups (p < 0.05). Conclusions This study suggests that combination therapy of intracerebral transplantation SB623 cells and voluntary exercise with RW achieves robust neurological recovery and synergistically promotes endogenous ...
Keywords	Cerebral ischemic infarct ; Rehabilitation ; Regenerative medicine ; SB623 ; Voluntary exercise ; Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
Subject code	610
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Correction

Stem Cell Research & Therapy, Vol 14, Iss 1, Pp 1-

Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic stroke

2023 Volume 1

Keywords	Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cell Therapy for Parkinson’s Disease

Takao Yasuhara / Masahiro Kameda / Tatsuya Sasaki / Naoki Tajiri / Isao Date

Cell Transplantation, Vol

2017 Volume 26

Abstract: Cell therapy for Parkinson’s disease (PD) began in 1979 with the transplantation of fetal rat dopamine-containing neurons that improved motor abnormalities in the PD rat model with good survival of grafts and axonal outgrowth. Thirty years have passed ... ...

Abstract	Cell therapy for Parkinson’s disease (PD) began in 1979 with the transplantation of fetal rat dopamine-containing neurons that improved motor abnormalities in the PD rat model with good survival of grafts and axonal outgrowth. Thirty years have passed since the 2 clinical trials using cell transplantation for PD patients were first reported. Recently, cell therapy is expected to develop as a realistic treatment option for PD patients owing to the advancement of biotechnology represented by pluripotent stem cells. Medication using levodopa, surgery including deep brain stimulation, and rehabilitation have all been established as current therapeutic strategies. Strong therapeutic effects have been demonstrated by these treatment methods, but they have been unable to stop the progression of the disease. Fortunately, cell therapy might be a key for true neurorestoration. This review article describes the historical development of cell therapy for PD, the current status of cell therapy, and the future direction of this treatment method.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2017-09-01T00:00:00Z
Publisher	SAGE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Combination of Ad-SGE-REIC and bevacizumab modulates glioma progression by suppressing tumor invasion and angiogenesis.

Yasuhiko Hattori / Kazuhiko Kurozumi / Yoshihiro Otani / Atsuhito Uneda / Nobushige Tsuboi / Keigo Makino / Shuichiro Hirano / Kentaro Fujii / Yusuke Tomita / Tetsuo Oka / Yuji Matsumoto / Yosuke Shimazu / Hiroyuki Michiue / Hiromi Kumon / Isao Date

PLoS ONE, Vol 17, Iss 8, p e

2022 Volume 0273242

Abstract: Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor and its overexpression has been shown to exert anti-tumor effects as a therapeutic target gene in many human cancers. Recently, we demonstrated the anti-glioma effects ...

Abstract	Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor and its overexpression has been shown to exert anti-tumor effects as a therapeutic target gene in many human cancers. Recently, we demonstrated the anti-glioma effects of an adenoviral vector carrying REIC/Dkk-3 with the super gene expression system (Ad-SGE-REIC). Anti-vascular endothelial growth factor treatments such as bevacizumab have demonstrated convincing therapeutic advantage in patients with glioblastoma. However, bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma. In this study, we examined the effects of Ad-SGE-REIC on glioma treated with bevacizumab. Ad-SGE-REIC treatment resulted in a significant reduction in the number of invasion cells treated with bevacizumab. Western blot analyses revealed the increased expression of several endoplasmic reticulum stress markers in cells treated with both bevacizumab and Ad-SGE-REIC, as well as decreased β-catenin protein levels. In malignant glioma mouse models, overall survival was extended in the combination therapy group. These results suggest that the combination therapy of Ad-SGE-REIC and bevacizumab exerts anti-glioma effects by suppressing the angiogenesis and invasion of tumors. Combined Ad-SGE-REIC and bevacizumab might be a promising strategy for the treatment of malignant glioma.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2022-01-01T00:00:00Z
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: Depolarization time and extracellular glutamate levels aggravate ultraearly brain injury after subarachnoid hemorrhage

Satoshi Murai / Tomohito Hishikawa / Yoshimasa Takeda / Yasuko Okura / Miki Fushimi / Hirokazu Kawase / Yu Takahashi / Naoya Kidani / Jun Haruma / Masafumi Hiramatsu / Kenji Sugiu / Hiroshi Morimatsu / Isao Date

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 11

Abstract: Abstract Early brain injury after aneurysmal subarachnoid hemorrhage (SAH) worsens the neurological outcome. We hypothesize that a longer duration of depolarization and excessive release of glutamate aggravate neurological outcomes after SAH, and that ... ...

Abstract	Abstract Early brain injury after aneurysmal subarachnoid hemorrhage (SAH) worsens the neurological outcome. We hypothesize that a longer duration of depolarization and excessive release of glutamate aggravate neurological outcomes after SAH, and that brain hypothermia can accelerate repolarization and inhibit the excessive release of extracellular glutamate and subsequent neuronal damage. So, we investigated the influence of depolarization time and extracellular glutamate levels on the neurological outcome in the ultra-early phase of SAH using a rat injection model as Experiment 1 and then evaluated the efficacy of brain hypothermia targeting ultra-early brain injury as Experiment 2. Dynamic changes in membrane potentials, intracranial pressure, cerebral perfusion pressure, cerebral blood flow, and extracellular glutamate levels were observed within 30 min after SAH. A prolonged duration of depolarization correlated with peak extracellular glutamate levels, and these two factors worsened the neuronal injury. Under brain hypothermia using pharyngeal cooling after SAH, cerebral perfusion pressure in the hypothermia group recovered earlier than that in the normothermia group. Extracellular glutamate levels in the hypothermia group were significantly lower than those in the normothermia group. The early induction of brain hypothermia could facilitate faster recovery of cerebral perfusion pressure, repolarization, and the inhibition of excessive glutamate release, which would prevent ultra-early brain injury following SAH.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Translating regenerative medicine techniques for the treatment of epilepsy

Takao Yasuhara / Isao Date / M Grant Liska / Yuji Kaneko / Fernando L Vale

Brain Circulation, Vol 3, Iss 3, Pp 156-

2017 Volume 162

Abstract: Epilepsy is considered a chronic neurological disorder and is accompanied by persistent and diverse disturbances in electrical brain activity. While antiepileptic pharmaceuticals are still the predominant treatment for epilepsy, the advent of numerous ... ...

Abstract	Epilepsy is considered a chronic neurological disorder and is accompanied by persistent and diverse disturbances in electrical brain activity. While antiepileptic pharmaceuticals are still the predominant treatment for epilepsy, the advent of numerous surgical interventions has further improved outcomes for patients. Despite these advancements, a subpopulation continues to experience intractable seizures which are resistant to current conventional and nonconventional therapeutic options. In this review, we begin with an introduction to the clinical presentation of epilepsy before discussing the clinically relevant laboratory models of epilepsy. Finally, we explore the implications of regenerative medicine – including cell therapy, neuroprotective agents, and electrical stimulation – for epilepsy, supplemented with our laboratory's data. This paper is a review article. Referred literature in this paper has been listed in the references section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.
Keywords	central nervous system disorders ; electrical stimulation ; epilepsy ; neurogenesis ; neuroprotective agents ; regenerative medicine ; stem-cell therapy ; Medical technology ; R855-855.5 ; Diseases of the circulatory (Cardiovascular) system ; RC666-701
Subject code	616
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Wolters Kluwer Medknow Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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