研究者詳細 - 山下　徹

論文 - 山下　徹

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Human Cord Blood-Endothelial Progenitor Cells Alleviate Intimal Hyperplasia of Arterial Damage in a Rat Stroke Model. 査読国際誌

Hongming Sun, Ryuta Morihara, Tian Feng, Zhihong Bian, Haibo Yu, Xiao Hu, Xinran Hu, Yuting Bian, Ryo Sasaki, Yusuke Fukui, Mami Takemoto, Taijun Yunoki, Yumiko Nakano, Koji Abe, Toru Yamashita

Cell transplantation 32 9636897231193069 - 9636897231193069 2023年

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Human cord blood-endothelial progenitor cells (hCB-EPCs) isolated from the human umbilical cord can be used to repair damaged arteries. In this study, we used an animal model with pathological changes that mimics artery wall damage caused by stent retrievers in humans. We injected hCB-EPCs to investigate their effect on endothelial hyperplasia and dysfunction during intimal repair. Four groups were established based on the length of reperfusion (3 and 28 days), as well as the presence or absence of hCB-EPC therapy. Damage to the internal carotid artery was evaluated by hematoxylin-eosin and immunohistochemical staining. Stroke volume was not significantly different between non-EPC and EPC groups although EPC treatment alleviated intimal hyperplasia 28 days after intimal damage. Vascular endothelial growth factor (VEGF) and eNOS expression were significantly higher in the EPC-treated group than in the non-EPC group 3 days after intimal damage. In addition, MMP9 and 4HNE expression in the EPC-treated group was significantly lower than in the non-EPC group. Ultimately, this study found that venous transplantation of hCB-EPCs could inhibit neointimal hyperplasia, alleviate endothelial dysfunction, suppress intimal inflammation, and reduce oxidative stress during healing of intimal damage.

DOI： 10.1177/09636897231193069

Safety and Clinical Effects of a Muse Cell-Based Product in Patients With Amyotrophic Lateral Sclerosis: Results of a Phase 2 Clinical Trial. 査読国際誌

Toru Yamashita, Yumiko Nakano, Ryo Sasaki, Koh Tadokoro, Yoshio Omote, Taijun Yunoki, Yuko Kawahara, Namiko Matsumoto, Yuki Taira, Chika Matsuoka, Ryuta Morihara, Koji Abe

Cell transplantation 32 9636897231214370 - 9636897231214370 2023年

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of motor neurons. Multilineage-differentiating stress-enduring (Muse) cells are unique endogenous stem cells that show therapeutic effects on motor function in ALS mouse models. We conducted a single-center open phase II clinical trial to evaluate the safety and clinical effects of repeated intravenous injections of an allogenic Muse cell-based product, CL2020, in patients with ALS. Five patients with ALS received CL2020 intravenously once a month for a total of six doses. The primary endpoints were safety and tolerability, and the secondary endpoint was the rate of change in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score. In addition, serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), sphingosine-1-phosphate (S1P), cerebrospinal fluid chitotriosidase-1 (CHIT-1), and neurofilament light chain (NfL) levels were evaluated. The CL2020 treatment was highly tolerated without serious side effects. The ALSFRS-R score change trended upward at 12 months post-CL2020 treatment compared with that at 3 months pre-administration, but the difference was not statistically significant. Among five patients diagnosed with ALS, three exhibited a decrease in the rate of ALSFRS-R score change, one demonstrated an increase, and another showed no change. In addition, the patients' serum IL-6 and TNF-α levels and cerebrospinal fluid CHIT-1 and NfL levels increased for up to 6 months post-treatment; however, their serum S1P levels continuously decreased over 12 months. These findings indicate a favorable safety profile of CL2020 therapy. In the near future, a double-blind study of a larger number of ALS patients should be conducted to confirm the efficacy of ALS treatment with CL2020.

DOI： 10.1177/09636897231214370

Tocovid Attenuated Oxidative Stress and Cognitive Decline by Inhibiting Amyloid-β-Induced NOX2 Activation in Alzheimer's Disease Mice. 国際誌

Zhihong Bian, Haibo Yu, Xinran Hu, Yuting Bian, Hongming Sun, Koh Tadokoro, Mami Takemoto, Taijun Yunoki, Yumiko Nakano, Yusuke Fukui, Ryuta Morihara, Koji Abe, Toru Yamashita

Journal of Alzheimer's disease : JAD 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: NADPH oxidase 2 (NOX2) is an important source of reactive oxygen species (ROS). Activated NOX2 may contribute to Alzheimer's disease (AD). Our previous studies showed that a novel vitamin E mixture, Tocovid, had potential neuroprotective effects in a stroke mice model and an AD cell model. OBJECTIVE: The aim of this study was two-fold: to assess whether long-term Tocovid treatment can regulate NOX2, and the therapeutic effects of long-term administration of Tocovid to an AD mice model. METHODS: Therapeutic effects of long-term administration of Tocovid (200 mg/kg /day) on an Aβ-overexpressed transgenic AD mice model (APP23, n = 8) was investigated. The therapeutic effect of Tocovid in 16-month-old mice compared with the no-treatment APP23 group (n = 9) was assessed. RESULTS: Tocovid treatment strongly improved motor and memory deficits of APP23 mice by attenuating NOX2 expression, oxidative stress, neuroinflammation, neurovascular unit dysfunction, synaptic alteration, and Aβ deposition after 16 months. CONCLUSION: These findings suggest that NOX2 is a potential target in AD pathology. Long-term administration of Tocovid may be a promising candidate for AD treatment.

DOI： 10.3233/JAD-220761

Cerebral syphilitic gumma mimicking a brain tumor that enlarged temporarily after commencing antibiotic treatment. 国際誌

Yoshiaki Takahashi, Nobutoshi Morimoto, Mizuki Morimoto, Shunsuke Mori, Yu Takahashi, Tomotsugu Ichikawa, Kyoko Yokota, Toru Yamashita

eNeurologicalSci 29 100436 - 100436 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

In this case report, we describe a 60-year-old man who presented with headaches for 1 year and mild confusion for 3 weeks and was initially diagnosed as having a cerebral tumor on the basis of finding a round lesion in the right lenticular nucleus with ring enhancement on gadolinium-enhanced T1-weighted brain magnetic resonance imaging. However, the discovery of positive serology for Treponema pallidum infection on routine tests on admission prompted analysis of cerebrospinal fluid, which was also positive on Treponema pallidum hemagglutination (TPHA), rapid plasma reagin (RPR), and treponemal antibody absorption (FTA-ABS) tests. Thus, he was diagnosed as having an intracranial syphilitic gumma. After commencing treatment with penicillin G, the lesion temporarily increased in size, but subsequently resolved completely with continuing antibiotic treatment. In the present era of increasing prevalence of syphilitic infection and because they are eminently treatable, syphilitic gummas should be included in the differential diagnosis of apparent brain tumors. Additionally, temporary enlargement of a probable gumma after instituting antibiotic treatment should not prompt cessation or change of the antibiotics.

DOI： 10.1016/j.ensci.2022.100436

Actual Telemedicine Needs of Japanese Patients with Neurological Disorders in the COVID-19 Pandemic.

Ryo Sasaki, Taijun Yunoki, Yumiko Nakano, Yusuke Fukui, Mami Takemoto, Ryuta Morihara, Koji Abe, Toru Yamashita

Internal medicine (Tokyo, Japan) 62 ( 3 ) 365 - 371 2022年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Objective During the coronavirus disease 2019 (COVID-19) pandemic, many social activities have moved online using applications for digital devices (e.g. computers, smartphones). We investigated the needs of telemedicine and trends in medical status and social care situations of Japanese patients with neurological disorders in order to estimate their affinity for an online telemedicine application. Methods We designed an original questionnaire for the present study that asked participants what problems they had with hospital visits, how the COVID-19 pandemic had affected their lives, and whether or not they would like to receive telemedicine. Patients The present study included volunteer caregivers, participants with Parkinson's disease (PD), epilepsy, stroke, dementia, immune-mediated neurological disease (IMMD), spinocerebellar degeneration (SCD), amyotrophic lateral sclerosis (ALS), headache, myopathy, and other neurological diseases from Okayama University Hospital. Results A total of 29.6% of patients wanted to use telemedicine. Patients with headaches (60.0%) and epilepsy (38.1%) were more likely to want to use telemedicine than patients with PD (17.8%) or stroke (19.0%). Almost 90% of patients had access to a digital device, and there was no association between favoring telemedicine, ownership of a digital device, hospital visiting time, or waiting time at the hospital, although age was associated with motivation to telemedicine use (52.6 vs. 62.2 years old, p <0.001*). Conclusion We can contribute to the management of the COVID-19 pandemic and the medical economy by promoting telemedicine, especially for young patients with headaches or epilepsy.

DOI： 10.2169/internalmedicine.9702-22

Novel <scp> ABCD1 </scp> mutation detected in a symptomatic female carrier of adrenoleukodystrophy

Yumiko Nakano, Yuki Taira, Ryo Sasaki, Koh Tadokoro, Taijun Yunoki, Emi Nomura, Yusuke Fukui, Mami Takemoto, Ryuta Morihara, Nobuyuki Shimozawa, Toru Yamashita

Neurology and Clinical Neuroscience 11 ( 1 ) 58 - 60 2022年10月

掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

We report a case of a symptomatic female carrier of X-linked adrenoleukodystrophy (ALD) with a novel ABCD1 gene mutation. She has developed slowly progressive gait disturbance since age 40, and her father and sister had similar symptoms. When admitted to our hospital at age 66, blood analysis showed slight increase of very long-chain fatty acids (VLCFA), and DNA analysis of ABCD1 gene revealed a novel heterozygous missense mutation (c.1700 A>C, p.Gln567Pro). The genetic testing for ABCD1 gene can be considered in female patients over middle age presenting spastic gait, because female ALD carriers tend to be symptomatic beyond age 60.

DOI： 10.1111/ncn3.12667

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/ncn3.12667

Protective and anti-oxidative effects of curcumin and resveratrol on Aβ-oligomer-induced damage in the SH-SY5Y cell line. 国際誌

Haibo Yu, Toru Yamashita, Xiao Hu, Zhihong Bian, Xinrang Hu, Tian Feng, Koh Tadokoro, Ryuta Morihara, Koji Abe

Journal of the neurological sciences 441 120356 - 120356 2022年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Alzheimer's disease (AD) is a degenerative disorder characterized by the loss of synapses and neurons in the brain, and results in the accumulation of amyloid-based neurotic plaques. Amyloid-β oligomers (AβO) are widely accepted as the main neurotoxin that induces oxidative stress and neuronal loss in AD. In this study, an oxidative stress model of the neuroblastoma SH-SY5Y cell line exposed to AβO was established to simulate an AD cell model. Exposure to AβO significantly reduced the viability of cultured SH-SY5Y cells (p < 0.05) and significantly increased intracellular reactive oxygen species (ROS) (p < 0.01). AβO exposure also induced oxidative stress in SH-SY5Y cells. Furthermore, AβO significantly increased the level of hyperphosphorylation of tau at sites T181 and T205 in SH-SY5Y cells (p < 0.01). Using edaravone, a free radical scavenger with neuroprotective properties, as the control, the possible protective and anti-oxidative effects of curcumin (40 μM) and resveratrol (20 μM) were evaluated. The results suggest that curcumin and resveratrol decreased ROS generation, attenuated oxidative stress, inhibited tau hyperphosphorylation, and protected SH-SY5Y cells from AβO damage. Both curcumin and resveratrol are promising supplements or medicine as therapeutic agents for the treatment of AD.

DOI： 10.1016/j.jns.2022.120356

Japanese case of Charcot-Marie-Tooth disease type 2Z with severe retinitis pigmentosa

Emi Nomura, Koh Tadokoro, Ryo Sasaki, Yumi Nakata, Yumiko Nakano, Taijun Yunoki, Mami Takemoto, Ryuta Morihara, Masahiro Ando, Hiroshi Takashima, Toru Yamashita

NEUROLOGY AND CLINICAL NEUROSCIENCE 10 ( 5 ) 266 - 268 2022年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Charcot-Marie-Tooth disease type 2Z (CMT2Z) shows highly variable clinical features. We report the first Japanese CMT2Z patient with a c.754C>T (p.R252W) substitution of the MORC2 gene, complicating severe retinitis pigmentosa. The MORC2 mutants were involved in a decrease in cell survival through induction of apoptosis. Thus, the MORC2 mutation might be involved in the degeneration of photoreceptors and the development of retinitis pigmentosa.

DOI： 10.1111/ncn3.12660

A case of successful renal transplantation of Charcot-Marie-Tooth disease associated with FSGS due to mutation of the INF2 gene

Chika Matsuoka, Yuki Taira, Ryo Sasaki, Namiko Matsumoto, Koh Tadokoro, Emi Nomura, Yuko Kawahara, Mami Takemoto, Ryuta Morihara, Akihiro Hashiguchi, Hiroshi Takashima, Hidemi Takeuchi, Motoo Araki, Koji Abe, Toru Yamashita

Neurology and Clinical Neuroscience 10 ( 5 ) 252 - 254 2022年9月

掲載種別：研究論文（学術雑誌）

Focal and segmental areas of glomerular sclerosis (FSGS) have various subcategories. Here, we report on a 35-year-old man who suffered from Charcot-Marie-Tooth disease (CMT) with FSGS carrying the INF2 mutation (c.206 T > C, p.L69P). The INF2 mutation might cause abnormal actin filaments of the podocytes and Schwann cells, leading to CMT associated with FSGS. He successfully underwent living donor kidney transplantation from a mother with a normal INF2 gene without any serious adverse events. Following genetic testing, the identification of the INF2 mutation allows a recipient to reduce the use of immunosuppressive drugs. Genetic testing may provide a treatment plan for kidney transplantation.

DOI： 10.1111/ncn3.12651

An NEFH founder mutation causes broad phenotypic spectrum in multiple Japanese families. 国際誌

Masahiro Ando, Yujiro Higuchi, Yuji Okamoto, Junhui Yuan, Akiko Yoshimura, Jun Takei, Takaki Taniguchi, Yu Hiramatsu, Yusuke Sakiyama, Akihiro Hashiguchi, Eiji Matsuura, Hiroto Nakagawa, Ken Sonoda, Toru Yamashita, Akiko Tamura, Hideo Terasawa, Jun Mitsui, Hiroyuki Ishiura, Shoji Tsuji, Hiroshi Takashima

Journal of human genetics 67 ( 7 ) 399 - 403 2022年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIMS: Mutations in neurofilament genes have been linked to several neuromuscular disorders. The neurofilament heavy (NEFH) gene was identified as the causative gene of Charcot-Marie-Tooth disease type 2CC (CMT2CC) in 2016, with a toxic gain of function mechanism caused by the translation and aggregation of cryptic amyloidogenic element (CAE) in the 3' untranslated region (UTR). But the NEFH-related clinical and genetic spectrums are still unclear in Japan. METHODS: We analyzed all variants in the NEFH gene from our in-house whole-exome sequencing data, established from Japanese nationwide patients with neuromuscular disorders, including Charcot-Marie-Tooth (CMT) disease and spinal muscular atrophy (SMA). RESULTS: We identified a c.3017dup (p.Pro1007Alafs*56) variant in NEFH from three families clinically diagnosed with CMT, and one family with SMA. In addition to the patients presented with typical peripheral neuropathies, pyramidal signs were observed from one CMT patient. Whereas the SMA patients showed severe characteristic weakness of triceps brachii and quadriceps femoris. All of these four families reside in Kagoshima Prefecture of Japan, and a following haplotype analysis strongly suggests a founder effect. INTERPRETATION: This is the original report referring to a founder mutation in NEFH. The clinical diversity in our study, comprising CMT, with or without pyramidal signs, and SMA, suggest an extensive involvement of peripheral nerve, anterior horn cells, or both. Our findings broaden the phenotypic spectrum of NEFH-related disorders.

DOI： 10.1038/s10038-022-01019-y

Efficacy and safety of spot heating and ultrasound irradiation on in vitro and in vivo thrombolysis models. 国際誌

Ryuta Morihara, Toru Yamashita, Yosuke Osakada, Tian Feng, Xinran Hu, Yusuke Fukui, Koh Tadokoro, Mami Takemoto, Koji Abe

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 42 ( 7 ) 1322 - 1334 2022年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

The feasibility of transcranial sonothrombolysis has been demonstrated, although little is known about the relationships between thermal or mechanical mechanisms and thrombolytic outcomes. Therefore, the present study aims to reveal the effect and safety of temperature and ultrasound through in vitro and in vivo thrombolysis models. Artificial clots in microtubes were heated in a water bath or sonicated by ultrasound irradiation, and then clots weight decrease with rising temperature and sonication time was confirmed. In the in vitro thrombotic occlusion model, based on spot heating, clot volume was reduced and clots moved to the distal side, followed by recanalization of the occlusion. In the in vivo study, the common carotid artery of rats was exposed to a spot heater or to sonication. No brain infarct or brain blood barrier disruption was shown, but endothelial junctional dysintegrity and an inflammatory response in the carotid artery were detected. The present spot heating and ultrasound irradiation models seem to be effective for disintegrating clots in vitro, but the safety of the in vivo model was not fully supported by the data. However, the data indicates that a shorter time exposure could be less invasive than a longer exposure.

DOI： 10.1177/0271678X221079127

Neuroprotective and Therapeutic Effects of Tocovid and Twendee-X on A beta Oligomer-Induced Damage in the SH-SY5Y Cell Line 国際誌

Xiao Hu, Toru Yamashita, Haibo Yu, Zhihong Bian, Xinran Hu, Tian Feng, Koh Tadokoro, Ryuta Morihara, Koji Abe

NEURODEGENERATIVE DISEASES 21 ( 5-6 ) 117 - 125 2022年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：KARGER

BACKGROUND: Alzheimer's disease (AD) is the most frequent cause of dementia among the elderly. The accumulation of amyloid beta (Aβ) and its downstream pathological events such as oxidative stress play central roles in AD. Recent studies revealed that Aβ oligomer (AβO)-induced strong neurotoxicity in SH-SY5Y cells via the induction of oxidative stress. OBJECTIVE: In the present study, we investigated the effect of two antioxidants, Tocovid and Twendee-X, on AβO-induced SH-SY5Y cell damage. METHODS: AβOs (2.5 μM) were applied to induce cellular damage in the SH-SY5Y cell line. Cell viability following AβO toxicity, Tau protein phosphorylation, cell morphology, and intracellular reactive oxygen species were assayed with or without different concentrations of Tocovid or Twendee-X. RESULTS: Tocovid (60 μg/mL) and Twendee-X (150 μg/mL) significantly recovered cell viability from AβO toxicity (**p < 0.01, vs. control), attenuated Tau protein phosphorylation (**p < 0.01, vs. AβOs), improved cell morphology (**p < 0.01, vs. AβOs), and suppressed intracellular ROS (**p < 0.01, vs. AβOs) in SH-SY5Y cells. CONCLUSION: These findings suggest the neuroprotective and therapeutic potential of Tocovid and Twendee-X for AD treatment.

DOI： 10.1159/000523983

A Japanese case of successful surgical resection of cerebral cavernous malformations with a CCM2 mutation

Emi Nomura, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yumiko Nakano, Taijun Yunoki, Ryuta Morihara, Tatsuya Sasaki, Hiroyuki Akagawa, Koji Abe, Toru Yamashita

NEUROLOGY AND CLINICAL NEUROSCIENCE 10 ( 5 ) 255 - 258 2022年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Cerebral cavernous malformations (CCMs) are congenital abnormalities of cerebral vessels. Surgical resection is rarely considered for the control of epilepsy in a first seizure patient with vascular malformation. In contrast, lesions that produce repetitive or progressive symptoms should be considered for surgical resection as treatment. Herein, we report a Japanese patient with a CCM2 mutation, c.609G>A (p.K203K) substitution, who showed drug-resistant epilepsy and dramatic improvement after surgical resection.

DOI： 10.1111/ncn3.12649

Clinical and Pathological Benefits of Scallop-Derived Plasmalogen in a Novel Mouse Model of Alzheimer's Disease with Chronic Cerebral Hypoperfusion. 国際誌

Tian Feng, Xinran Hu, Yusuke Fukui, Zhihong Bian, Yuting Bian, Hongming Sun, Mami Takemoto, Taijun Yunoki, Yumiko Nakano, Ryuta Morihara, Koji Abe, Toru Yamashita

Journal of Alzheimer's disease : JAD 86 ( 4 ) 1973 - 1982 2022年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The oral ingestion of scallop-derived plasmalogen (sPlas) significantly improved cognitive function in Alzheimer's disease (AD) patients. OBJECTIVE: However, the effects and mechanisms of sPlas on AD with chronic cerebral hypoperfusion (CCH), a class of mixed dementia contributing to 20-30% among the dementia society, were still elusive. METHODS: In the present study, we applied a novel mouse model of AD with CCH to investigate the potential effects of sPlas on AD with CCH. RESULTS: The present study demonstrated that sPlas significantly recovered cerebral blood flow, improved motor and cognitive deficits, reduced amyloid-β pathology, regulated neuroinflammation, ameliorated neural oxidative stress, and inhibited neuronal loss in AD with CCH mice at 12 M. CONCLUSION: These findings suggest that sPlas possesses clinical and pathological benefits for AD with CCH in the novel model mice. Furthermore, sPlas could have promising prevention and therapeutic effects on patients of AD with CCH.

DOI： 10.3233/JAD-215246

A case of a heterozygous ABCC6 mutation showing recurrent ischemic strokes and intracranial hemorrhages

Emi Nomura, Yuko Kawahara, Yoshio Omote, Yoshiaki Takahashi, Namiko Matsumoto, Ken Ikegami, Mami Takemoto, Nozomi Hishikawa, Yumiko Nakano, Taijun Yunoki, Ryuta Morihara, Masahiro Uemura, Koji Abe, Toru Yamashita

Neurology and Clinical Neuroscience 10 ( 2 ) 98 - 101 2022年3月

掲載種別：研究論文（学術雑誌）

Mutations in the ATP-binding cassette subfamily C member 6 (ABCC6) gene are responsible for pseudoxanthoma elasticum (PXE). PXE is a rare genetic metabolic disease with autosomal recessive inheritance that shows ectopic mineralization in skin, eyes, and blood vessels and causes cerebrovascular disease. There are few reports of intracranial hemorrhages in patients with the ABCC6 mutation. We report the first Japanese case with a heterozygous ABCC6 mutation displaying recurrent ischemic strokes and intracranial hemorrhages. We propose that the ABCC6 mutation may be one cause of neurovascular diseases with a family history.

DOI： 10.1111/ncn3.12575

Chronic Beneficial Effect of Makeup Therapy on Cognitive Function of Dementia and Facial Appearance Analyzed by Artificial Intelligence Software. 国際誌

Koh Tadokoro, Toru Yamashita, Junko Sato, Yoshio Omote, Mami Takemoto, Ryuta Morihara, Koichiro Nishiura, Tomiko Tani, Koji Abe

Journal of Alzheimer's disease : JAD 85 ( 3 ) 1189 - 1194 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Makeup greatly impacts normal social lives but can also be a non-pharmacological form of therapy for dementia. OBJECTIVE: To evaluate the therapeutic effect of makeup therapy. METHODS: We carried out a prospective interventional study on female nursing home residents with dementia, focusing on the chronic therapeutic effect of makeup therapy. Thirty-four patients who received either only skin care (control group, n = 16) or skin care plus makeup therapy (makeup therapy group, n = 18) once every 2 weeks for 3 months were assessed. RESULTS: Three months of makeup therapy significantly improved the Mini-Mental State Examination (MMSE) score compared with control patients ( *p < 0.05). Artificial intelligence (AI) software revealed that the appearance of age decreased significantly in the makeup group compared with the control, especially among patients without depression ( *p < 0.05). Furthermore, a larger AI happiness score was significantly correlated with a greater improvement of ADL in the makeup therapy group (r = 0.43, *p < 0.05). CONCLUSION: Makeup therapy had a chronic beneficial effect on the cognitive function of female dementia patients, while the chronic effect of makeup therapy on facial appearance was successfully detected by the present AI software.

DOI： 10.3233/JAD-215385

Protective Effect of Rivaroxaban Against Amyloid Pathology and Neuroinflammation Through Inhibiting PAR-1 and PAR-2 in Alzheimer's Disease Mice. 国際誌

Zhihong Bian, Xia Liu, Tian Feng, Haibo Yu, Xiao Hu, Xinran Hu, Yuting Bian, Hongming Sun, Koh Tadokoro, Mami Takemoto, Taijun Yunoki, Yumiko Nakano, Yusuke Fukui, Ryuta Morihara, Koji Abe, Toru Yamashita

Journal of Alzheimer's disease : JAD 86 ( 1 ) 111 - 123 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Recent studies have revealed that atrial fibrillation (AF) patients have a high risk of developing cognitive impairment, vascular dementia, and Alzheimer's disease (AD). Some reports suggest that the application of oral anticoagulant with an appropriate dose may have a preventive effect on AD. However, which oral anticoagulant drug is more appropriate for preventing AD and the underlying mechanism(s) is still unknown. OBJECTIVE: The aim of the present study was to assess the treatment effect of rivaroxaban administration as well as investigate the roles of PAR-1 and PAR-2 in the AD + CAA mice model. METHODS: In the present study, we compared a traditional oral anticoagulant, warfarin, and a direct oral anticoagulant (DOAC), rivaroxaban, via long-term administration to an AD with cerebral amyloid angiopathy (CAA) mice model. RESULTS: Rivaroxaban treatment attenuated neuroinflammation, blood-brain barrier dysfunction, memory deficits, and amyloid-β deposition through PAR-1/PAR-2 inhibition in the AD + CAA mice model compared with warfarin and no-treatment groups. CONCLUSION: The present study demonstrates that rivaroxaban can attenuate AD progress and can be a potential choice to prevent AD.

DOI： 10.3233/JAD-215318

Three cases of GFAP astrocytopathy, one with bilateral ovarian teratoma

Yosuke Osakada, Yoshio Omote, Yuki Taira, Chika Matsuoka, Ken Ikegami, Koh Tadokoro, Emi Nomura, Yuko Kawahara, Kota Sato, Yuka Terasawa, Nozomi Hishikawa, Ryuta Morihara, Mami Takemoto, Akio Kimura, Takayoshi Shimohata, Toru Yamashita, Koji Abe

Neurology and Clinical Neuroscience 10 ( 1 ) 30 - 34 2021年11月

掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

Glial fibrillary acidic protein (GFAP) astrocytopathy is a novel autoimmune meningoencephalomyelitis. Case 1 is a 26–year-old (yo) woman with a bilateral ovarian teratoma. She presented neck stiffness, hyperreflexia, bilateral postural tremor, and urinary retention. Three courses of a methylprednisolone pulse and subsequent enucleation of the bilateral ovarian teratoma improved her neurological symptoms with no recurrence. Case 2 is a 46-year-old man who showed infectious-like symptoms with elevated creatine kinase. Case 3 is a 76-year-old man with preceding weight loss, a hyperintensity lesion in the hypothalamus, and increased uptake of the spinal cord, assessed by Fluorine18 fluorodeoxyglucose positron emission tomography (18F-FDG PET). We compared the clinical features of the present three cases with previous reports. Consciousness disturbance, neck stiffness, tremors, and urinary dysfunction were observed in all three cases. These findings suggest widespread damage of the brain and spinal cord.

DOI： 10.1111/ncn3.12559

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/ncn3.12559

Accelerated accumulation of fibrinogen peptide chains with Aβ deposition in Alzheimer's disease (AD) mice and human AD brains. 国際誌

Zhihong Bian, Toru Yamashita, Xiaowen Shi, Tian Feng, Haibo Yu, Xiao Hu, Xinran Hu, Yuting Bian, Hongming Sun, Koh Tadokoro, Mami Takemoto, Yoshio Omote, Ryuta Morihara, Koji Abe

Brain research 1767 147569 - 147569 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Alzheimer's disease (AD) is a common neurodegenerative disease that is characterized by the abnormal accumulation of intracellular and extracellular amyloid-β (Aβ) as well as disruption of the blood brain barrier (BBB). Fibrinogen plays an essential role in regulating thrombosis, wound healing, and other biological functions. In the present study, we investigated the relationship between three polypeptide chains α, β, and γ (FGA, FGB, and FGG) and Aβ deposition in the APP23 plus chronic cerebral hypoperfusion (CCH) mice model as well as the human AD brain. FGA, FGB, and FGG accumulated when Aβ was deposited in neural cells and cerebral vessels. This deposition was significantly higher in AD plus CCH mice models relative to wild-type brains, and in human AD brains compared to control brains. The present study demonstrates that FGA, FGB, and FGG are associated with AD progress, and can thus be potential targets for the diagnosis and therapy of AD.

DOI： 10.1016/j.brainres.2021.147569

Neuroprotective effects of Scallop-derived plasmalogen in a mouse model of ischemic stroke. 国際誌

Tian Feng, Xinran Hu, Yusuke Fukui, Koh Tadokoro, Zhihong Bian, Ryuta Morihara, Toru Yamashita, Koji Abe

Brain research 1766 147516 - 147516 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Scallop-derived plasmalogen (sPlas) has both anti-oxidative and anti-inflammation activities, but its efficacy has not been investigated in ischemic stroke models where oxidative stress, inflammation, and neurovascular unit (NVU) damage accelerates pathophysiological progression. Therefore, in the present study, we aimed to assess the neuroprotective effects of sPlas in ischemic stroke by using a transient middle cerebral artery occlusion (tMCAO) mouse model. After the pretreatment of vehicle or sPlas (10 mg/kg/day) for 14 days, adult male mice were subjected to tMCAO for 60 min, then continuously treated with vehicle or sPlas during reperfusion and for an additional 5 days. The administration of sPlas significantly improved motor deficits (corner and rotarod tests, *p < 0.05 vs vehicle), enhanced serum antioxidative activity (OXY-adsorbent and d-ROMs tests, *p < 0.05 vs vehicle), reduced infarction volume (*p < 0.05 vs vehicle), decreased the expression of two oxidative stress markers, 4-HNE (*p < 0.05 vs vehicle) and 8-OHdG (*p < 0.05 vs vehicle), decreased the expression of pro-inflammatory markers Iba-1 (**p < 0.01 vs vehicle), IL-1β (**p < 0.01 vs vehicle), and TNF-α (**p < 0.01 vs vehicle), and alleviated NVU damage (collagen IV, MMP9, and GFAP/collagen IV, *p < 0.05 vs vehicle). Our present findings are the first to demonstrate the neuroprotective effects of sPlas on acute ischemic stroke mice at 5 d after tMCAO via anti-oxidative stress, anti-inflammation, and improvement of NVU damage, suggesting the potential of sPlas in preventing and treating ischemic stroke.

DOI： 10.1016/j.brainres.2021.147516

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