Pe-11-1
Co-transplantationofM2microgliaandneuralstem cellimprovesthepathologyofcerebralischemia○AbdullahM.Sheikh,ShingoMitaki,ShozoYano,ShateraTabassum,
YasukoWada,AtsushiNagai Shimane University, Japan
Background and purpose: Previous studied have demonstrated that neural stem cell （NSC） or microglia transplantation improves pathological conditions in stroke, but optimum progress was not achieved. The purpose of this study is to investigate whether co-transplantation of M2 type microglia could improve the beneficial effects of NSC transplantation. Methods and results:
Middle cerebral artery occlusion （MCAO） models were prepared using adult male Wister rats （n=20）. A microglia cell line （MG6） was treated for 16 h with IL-4 （10 ng/ml） to induce M2 phenotype （M2-MG6）. M2-MG6 was transplanted immediately after, and a NSC line （mpLTN3） 24 h after MCAO.
MRI and neurological severity scores revealed that M2-MG6 and mpLTN3 co-transplantation （n=10） did not decrease stroke volume or improve neurological performance when compared with mpLTN3-alone transplanted （n=10） MCAO model. However, hematoxylin and eosin staining revealed that cell infiltration was decreased in the core, and tissue damage was decreased in the penumbra area of M2-MG6 and mpLTN3 co-transplantation group. Immunostaining results demonstrated the presence of large size microglia in the ischemic core area of M2-MG6 and mpLTN3 co-transplantation group. Importantly, NSC and vessel number in the lesion area was increased in this group. Conclusion: Thus our results are suggesting that M2-MG6 could clear the damaged tissue from the lesion area in stroke condition by phagocytosis, which improve the condition for angiogenesis and NSC migration. Further study will be done to elucidate the detail mechanism.
Pe-11-2
AssociationofAdmittingNIHSSStatusandIn-hospitalOutcomesofFilipinoAcuteStrokePatients○Ma.CieloG.Peligrino,JarungchaiAntonS.Vatanagul Perpetual Succour Hospital, Philippines
Introduction:Stroke is a common cause of morbidity and mortality in the adult population worldwide. Early identification of level of disability is of use in planning for the long term care.The most widely used and easily learned predictor of disposition is the National Institute of Health Stroke Scale （NIHSS）.
Objective:Determine association of admitting NIHSS to in-hospital outcomes of Filipino stroke patients. To know the demographics,comorbidities,in-hospital complications. Methods:Includes patients who presented with less than 24 hrs focal neurologic deficit with imaging. NIHSS score done to the study population at admission.On the day of discharge,functional status taken using modified Rankin Scale.In-hospital complications and length of hospital stay were noted.
Results:Sixty stroke patients were analyzed. There was significant association with patients' NIHSS status and in-hospital outcome （p less than 0.05）,higher ratio of mortalities had NIHSS more than 13（7/18 cases）.Demographics:47 percent were more than 65 years old,58 percent males,77percent BMI more than 25.Clinical profiles:73 percent hypertensive, 43 percent diabetic and 20 percent had atrial fibrillation（AF）. Hypertension was associated with mortality
（6/6 cases, p=0.015）.In-hospital complication most commonly encountered was pneumonia（18percent）.Stroke type was 75 ischemic and 25 hemorrhagic.
Conclusion:Admitting NIHSS predicts the in-hospital outcome after an acute stroke in Filipino subjects.Demographics:age group of above 65,gender-males,BMI above 25. Hypertensives had higher rate of in-hospital deaths.
Pe-11-4
ExplorationofOPCdifferentiationunderischemic strokeusingBCAS1immunohistochemistry○GuanhuaJiang,TakashiAyaki,TakakuniMaki,RyosukeTakahashi Department of Neurology, Kyoto University Graduate School of Medicine, Japan
Background: Brain tissue is especially vulnerable to ischemic insult, and ischemic injury evokes cell deaths as well as the glial response which involves activation of microglia, astrocytes, and oligodendrocyte. Oligodendrocytes are crucial for remyelination of damaged brain and differentiate from oligodendrocyte precursor cell （OPC）, which is an immature form of oligodendrocyte. It's been reported that OPCs are abundantly recruited to the ischemic region in ischemic animal models, however, it remains unclear how OPCs gather or distribute to an ischemic area, but fail to mature into functional oligodendrocytes in a human ischemic brain. Breast carcinoma amplified sequence 1 （BCAS1） is recently been proved to be highly expressed in newly formed, myelinating oligodendrocytes（pre-mOLGs）, and decreases in mature oligodendrocytes, which can be used to segregate them from OPC and mature oligodendrocytes. Here we investigate how OPCs and pre-mOLGs contribute to neurovascular damage and remodeling after stroke and the undergoing mechanisms of tissue injury and repair in a human brain. Methods:
Neuropathologic examinations and immunohistochemistry will be applied to human brain samples, including stroke subjects, healthy control subjects and VCI subjects, followed by light microscope observation. Result: In acute stage of ischemic stroke, BCAS1+ cells are significantly increased and clustered among the peri-ischemic area, with a less arborized morphology. Under chronic cerebral ischemia （eg. VCI）, the number of BCAS1+ cells are scattered and better differentiated.
Pe-11-6
Invivodirectreprogrammingmethodofglial linagetoneuronalcellsinpost-strokebrain○ToruYamashita,JingweiShang,YumikoNakano,RyutaMorihara,
KotaSato,MamiTakemoto,NozomiHishikawa,YasuyukiOhta,
KojiAbe
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
Background and Purpose- Somatic cells including intracerebral glial cells can be directly converted into induced neuronal cells （iNc） by enforced transcriptional factors such as Ascl1, Sox2, or NeuroD1. However, the therapeutic effect of in vivo direct reprogramming on ischemic stroke has not been evaluated. Methods- In the present study, a retroviral solution （1.5-2.0×
107 /ul） of mock pMX-GFP （n=13） or pMX-Ascl1/Sox2/NeuroD1 （ASN） （n=14）
was directly injected into the ipsilateral striatum and cortex 3 days after 30 min of transient cerebral ischemia. Results- The reprogrammed cells first expressed neuronal progenitor marker Dcx 7 and 21 days after viral injection, then expressed mature neuronal marker NeuN. This was accompanied by morphological changes, including long processes and synapse-like structures, 49 days after viral injection. Meanwhile, therapeutic improvement was not detected both in clinical scores or infarct volume. Conclusions- The present study provides a future novel self-repair strategy for ischemic stroke with beneficial modifications of the inducer-suppressor balance.
Pe-11-5
withdrawnPe-11-3
withdrwan一 般 演 題
ポ ス タ ー （ 英 語 ）
Pe-10-3
Redslowdetectedinscalp-EEGfrom epileptogeniczoneoftemporallobeepilepsy○MiwaTakatani1,MasaoMatsuhashi2,ShunsukeKajikawa1, MasayaTogo1,KiyohideUsami2,AkihiroShimotake1, TakefumiHitomi3,RyosukeTakahashi1,AkioIkeda2
1 Department of Neurology, Kyoto University Graduate School of Medicine, Japan, 2 Department of Epilepsy, Movement Disorders and Physiology, Kyoto University Graduate School of Medicine, 3 Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine
Background: Focal slow wave accompanied by High-frequency oscillations （HFOs） were associated with seizure onset zone （SOZ） in invasive electroencephalogram （EEG）, and we have coined this epileptic slow, "Red slow" （Inoue et al., 2018）. Objectives: We aimed to clarify the presence and clinical significance of Red slow in scalp EEG. We focused on Temporal intermittent rhythmic delta activity （TIRDA）, a potential EEG marker of epileptic activity in temporal lobe epilepsy （TLE）. Methods: We retrospectively evaluated clinical findings and scalp-recorded video-EEG monitoring data of 5 TLE patients from 2016 to 2018. For analysis of red slow, we collected up to 20 EEG segments with TIRDA in each patient. Then, we investigated 2 electrodes with the largest amplitude of TIRDA for each patient by using the time-frequency analysis and high-pass filtered waveform. Finally, we assessed the occurrence rate of fast oscillations with TIRDA at each electrode. Results: All patients had abnormal findings on MRI in the temporal lobe where TIRDA was detected, and the electrodes where we detected TIRDA also recorded interictal spikes. All patients showed seizures during the video-EEG monitoring, and 3 of them identified the seizure from the temporal area consistently.
We investigated 93 TIRDA. The occurrence rate of fast oscillations in these TIRDA were 0-35% （mean±SD: 10.86±11.75 times）. Conclusions: Slow wave with fast oscillations was found even in scalp EEG. Furthermore, the red slows were recorded in the electrodes considered to be SOZ because of the ictal and interictal EEG, MRI findings.
Pe-10-6
PlasmaprostaglandinD2synthaselevelsin sleepandneurologicaldiseases○KeisukeSuzuki,ShihoSuzuki,YukoIshii,MadokaOkamura, TakeoMatsubara,HiroakiFujita,NarihiroNozawa,SaroKobayashi, KoichiHirata
Department of Neurology, Dokkyo Medical University, Japan
Background: Prostaglandin D2 （PGD2）, which is the most abundant prostaglandin in the mammalian brain, promotes sleep and may play a role in sleep and neurological diseases. We assessed PGD synthase （PGDS） levels in patients with sleep and neurological disorders. Methods: This study included 63 patients with neurological or sleep disorders （Parkinson's disease with excessive daytime sleepiness （PDS）, n=19; PD without sleepiness （PDWS）, n=14; Alzheimer's disease （AD）, n=10; narcolepsy （NA）, n=10; sleep apnea syndrome （SAS）, n=10） and 21 healthy controls. Plasma lipocalin-type PGDS
（L-PGDS） and glutathione-dependent hematopoietic PGDS （H-PGDS） levels were determined using an enzyme-linked immunosorbent assay. Results:
H-PGDS levels did not significantly differ among the groups. Compared with healthy controls, the PDWS, PDS and AD groups had higher levels of L-PGDS.
Neither H-PGDS nor L-PGDS levels correlated with scores on the Epworth Sleepiness Scale or Pittsburgh Sleep Quality Index in any group. Conclusion:
We found higher levels of L-PGDS in patients with neurodegenerative diseases such as PD and AD.
Pe-10-4
withdrawnPe-10-8
withdrawn一 般 演 題
ポ ス タ ー （ 英 語 ）
Pe-10- 5
withdrawnPe-10- 7
withdrawnPe-11-8
Transplantationofamnioticmesenchymalstemcells amelioratesbraindamageaftercerebralischemia○ShiroTakahashi1,2,ChikakoNito1,YukiSakamoto1,
MasafumiArakawa1,2,SatoshiSuda1,YukoNitahara-kasahara2,3,
TakashiOkada3,KazumiKimura1
1 Department of Neurology, Graduate School of Medicine, Nippon Medical School, Japan, 2 Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Nippon Medical School, Japan, 3 Department of Cell and Gene Therapy, Graduate School of Medicine, Nippon Medical School [Objective] Several studies have focused on cell therapies by using embryonic stem cells to prevent brain injury after ischemia. The transplantation of human amnion-derived mesenchymal stem cells （AMSCs） yielded positive therapeutic outcomes in various animal models of diseases. In this study, we investigated the effects of intravenous AMSC administration after transient middle cerebral artery occlusion
（MCAO） in rats. [Methods] Male SD rats underwent transient 90 min MCAO. 1×106 AMSCs or vehicle were administered just after reperfusion （n=5, each）. The infarct and edema volume were measured 24 h after reperfusion. Neurological performance and survival rate were evaluated on days 1, 7 and 28 after transient MCAO. [Results]
Transplanted AMSCs significantly reduced infarct and edema volume （p<0.05, p<0.01）
and reversed motor deficits at 24 h after reperfusion （abnormal posture; p<0.01, hemiparesis; p<0.0001）. Compared with the saline group, animal treated with AMSCs exhibited improved neurological performance in the Rota -Rod test at 28 days after transient MCAO （p<0.01）. 2 rats treated with vehicle were dead （survival rate:60%）
and all rats could survive in the AMSC-treated group. [Conclusions] The present study shows that administration of human AMSCs immediately after reperfusion improved ischemic damage, neurological function and survival rate in a rodent model of focal cerebral ischemia. These results suggest that transplanted AMSCs would induce neuroprotection and functional recovery after ischemia/reperfusion injury.
Pe-12-1
Clinicalcharacteristicsofemergencypatients withdementiainalocalclinic○KohTadokoro1,2,RyoSasaki1,2,YosukeWakutani2,YoshikiTakao1,
YoshioOmote1,MamiTakemoto1,NozomiHishikawa1,
YasuyukiOhta1,ToruYamashita1,KojiAbe1
1 Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan, 2 Department of Neurology, Kurashiki Heisei Hospital, Japan
[Objective] To clarify the clinical characteristics of emergency patients with dementia in a local clinic. [Methods] We retrospectively examined patients with dementia who visited our emergency clinic. Among 16,764 patients who visited our emergency clinic in 3 years from 2014 to 2017, we focused on 2,574 （15.4%） patients with dementia. [Results] The mean age of patients with dementia was 84.9 ± 0.1 years, which was much older than the age of the total emergency patients （58.1 ± 0.2 years）. The hospitalization rate was 54.9% for patients with dementia, which was more than double that of patients without dementia （23.3%; P < 0.01）, and was higher than that （44.3%） of patients who were aged 75 years old or older without dementia. Infection （42.4%） and falls
（20.9%） were the most common causes for emergency visits and hospitalization in the present study. Hospitalized patients with dementia spent a longer time in hospital for stroke （64.0 ± 5.3 days） and falls （51.9 ± 2.1 days） than those with those with infection, epilepsy, syncope, loss of consciousness, other causes
（P < 0.01）, or dehydration （P < 0.05）. [Conclusions] Emergency patients with dementia were commonly experienced in our clinic. These patients were older in age, had a higher hospitalization rate, and had a longer hospitalization, especially due to stroke and falls, than patients without dementia.
Pe-12-2
Tricetinaseffectiveantialzheimerspotentials throughforAChEandBChEenzymesinhibition○KanikaPatel,DineshKumarPatel
Sam Higginbottom University of Agriculture, Technology and Sciences, India
Objective: The most prevalent neurodegenerative disease is Alzheimer's disease （AD） and worldwide it is the most common cause of dementia. The aim of the present study is to identify phytoconstituents for the treatment of Alzheimer's disease through a AChE and BChE enzymes inhibition. Methods:
Various databases have been searched for the therapeutic potential of Tricetin in various animal models and in in-vitro study. All the data have been analyzed through various statistical methods to get proper correlation of Alzheimer's disease with acetylcholine level, oxidative stress, and inflammation. AChE and BChE inhibitory potential of Tricetin through in-silico molecular docking have been done to know their binding modes, drug likeness properties and inhibitory mechanisms. Results: Docking study results have confirmed that Tricetin have good affinity into AChE and BChE binding site. Consequently Tricetin reversibly inhibited AchE and BChE in a mixed-competitive manner. Glide Gscore and binding energies were calculated and found that a hydrophobic interaction of Tricetin with AChE and BuChE has been confirmed with low binding energies. Further In-vitro assays showed that Tricetin have better antioxidant potential which supports their possible role in Alzheimer's disease.
In-silico prediction of blood-brain barrier （BBB） permeation and ADMET properties of Tricetin was also reported in various databases. Conclusions:
This study could lead to the further development of potent acetylcholinesterase inhibitors for the treatment of Alzheimer's disease.
Pe-12-3
Acationicgalliumphthalocyanineinhibits amyloidbetapeptidefibrilformation○ShateraTabassum1,AbdullahM.Sheikh1,ShozoYano1,
TakahisaIkeue1,YoshieIto1,ShingoMitaki1,MakotoMichikawa2,
AtsushiNagai1
1 Shimane University, Japan, 2 Nagoya City University
Background: Amyloid β （Aβ） peptide deposition is considered as the main cause of Alzheimer's disease （AD）. Previously, we have found that a Zn containing neutral phthalocyanine （Zn-Pc） inhibits Aβ fibril formation.
Purpose: The purpose of this study is to investigate the effects of a cationic gallium containing Pc （GaCl-Pc） on Aβ fibril formation process. Methods and Result: Aβ fibril formation was induced by incubating synthetic A β peptides in fibril forming buffer, and the amount of fibril was evaluated by ThT fluorescence assay. GaCl-Pc dose-dependently inhibited both Aβ
1-40 and Aβ1-42 fibril formation. It mainly inhibited the elongation phase of A β1-42 fibril formation kinetics, but not the lag phase. Near infrared scanning result showed that GaCl-Pc had the ability to bind to Aβ1-42. But Western blotting results showed that it did not inhibit its oligomerization process. MTT assay demonstrated that GaCl-Pc did not show any toxicity in the culture of a neuronal cell line, rather it demonstrated protective effects on Aβ-induced toxicity. GaCl-Pc destabilized preformed Aβ1-42 fibrils dose dependently in vitro condition. Importantly, when incubated with brain slice culture （n=5） or non-fixed brain tissues （n=5） of APP transgenic AD mice （J20 strain）, GaCl-Pc decreased tissue Aβ level, as revealed by immunostaining. Conclusion:
Thus our result demonstrated that GaCl-Pc decreased Aβ aggregation and destabilized preformed fibril. Since cationic molecules show better ability to cross the blood brain barrier, cationic GaCl-Pc could be important for the therapy of AD.
Pe-12-4
NeuroprotectiveeffectsofGossypetininAlzheimer's disease:In-silicoandIn-vitroapproaches○DineshK.Patel,KanikaPatel
Department of Pharmaceutical Science, Shalom Institute of Health and Allied Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, India
Purpose: Gossypetin is a flavonoid which is basically flavone and found in hibiscus species. Acetylcholinestrase and butrylcholinesterase enzymes play an important role in the Alzheimers disease and inhibition of these enzymes are the key factors for the treatment of Alzhemers disease.Plant are valuable source of phytochemicals which can inhibit cholinestrase. Protective effects of gossypetin in the management of alzheimers disease have been investigated in the present work through inhibitory potential of gossypetin on cholinesterase.
Method: In order to understand the beneficial health aspect of gossypetin in brain related disorder, effect of gossypetin on cholinesterase enzymes have been investigated through In silico method. However present work also summarized the pharmacological properties of gossypetin with special reference to its effect on cholinesterase inhibitory potential. Results: From the data analysis it was found that gossypetin has antioxidant, antimutagenic, antiatherosclerotic, antimicrobial and cytoprotective properties. Docking study revealed the interaction of gossypetin with the pocket region of the cholinesterase enzymes. Further molecular docking study also revealed the probable mechanism of binding modes of inhibitors to cholinesterase.
Conclusion: These findings put more insights into understanding the interaction of gossypetin and cholinesterase enzymes. This work will be beneficial for the entire scientific person to find out more insights of gossypetin in alzheimers disease.
Pe-11-7
withdrawn一 般 演 題
ポ ス タ ー （ 英 語 ）
Pe-12-6
AnalysisofcerebralsmallvesselchangesinAD modelmice○AbuZaffarShibly1,SheikhM.Abdullah1,AbulKalamAzad1, XiaojingZhou1,ShingoMitaki1,MakotoMichikawa2,AtsushiNagai1
1 Shimane University, Faculty of Medicine, Japan, 2 Nagoya City University ,Graduate School of Medical Sciences
Objective: The objective of this study is to investigate time-dependent changes of small vessels in the brains of Alzheimer's disease （AD）. Methods: A total 40 AD model mice （amyloid precursor protein transgenic mice, J20 strain） were used in this study. Vascular and other pathological changes were analyzed from 3 to 9 months of age. Vessel density was evaluated by solanum tuberosum lectin （STL） staining, and vessel related molecules by immunostaining.
Results: At 3 months, amyloid β was detected in neurons and around the vessels of J20 mice brain. Compared to wild type littermate, the vessel density was decreased in hippocampus and cortex of J20 mice at 9 months. Claudin 5, Matrix metallopeptidase-9 （MMP-9） and vascular endothelial growth factor
（VEGF） were detected in vessels, where claudin 5 was decreased, and VEGF and MMP-9 were increased in hippocampus and cortex at 3 months. Collagen 4 staining did not show any difference between the groups. GFAP+ astrocyte number was increased in J20 mice, but the coverage of blood vessel by their end-feet was decreased at 9 months. A water channel protein aquaporin 4 was detected around the vessel in wild type mice, which spread beyond the vessel wall in J20 mice brain at hippocampus and cortex. Conclusions: This study showed that, an early decrease of tight junction protein was associated with increased MMP-9 and VEGF expression, indicating dysfunction of blood brain barrier. Decreased junction protein expression might cause leakage of blood constituents to the parenchyma that alter astrocyte polarity and its functions.
Pe-12-7
OraladministrationofPERAMPANELtoAlzheimer modelmicerapidlyloweredamyloid-betalevelsinISF○SakihoUeda1,2,AkiraKuzuya1,MasakazuMiyamoto1, AyaeKinoshita2,RyosukeTakahashi1
1 Department of Neurology, Kyoto University Graduate School of Medicine, Japan, 2 School of Human Health Sciences Faculty of Medicine Kyoto University, Japan
[Background]Hippocampal hyperexcitability can contribute to Alzheimer disease
（AD） pathophysiology at a very early stage.Proposing a vicious cycle model of AD linked to epileptic activity,we hypothesize that antagonizing AMPA receptors in AD reduce ISF monomeric amyloid-beta（Aβ） levels, resulting in slowing Aβ deposition.[Method]We have established brain in vivo microdialysis system that samples ISF over time from freely-moving APP transgenic mice（J20）.
Monomeric Aβ40 and Aβ42 levels in ISF were quantified by ELISA.First,ISF Aβ40 and Aβ42 levels were measured in either young J20 mice prior to Aβ deposition or elder J20 mice with Aβ plaques.Next,ISF Aβ40 and Aβ42 levels were measured over time in young J20 mice after a single oral administration of perampanel（PER）, a selective non-competitive AMPA receptor antagonist.[Result]
In elder J20 mice,both monomeric Aβ40 and Aβ42 levels were significantly decreased with the higher ratio of Aβ40 and Aβ42 as compared with young J20 mice,reflecting an age-dependent amyloidogenic shift of a dynamic equilibrium of Aβ forms toward aggregation state.In young J20 mice, a single oral administration of PER treatment decreased ISF Aβ levels in a dose-dependent manner with a reduction more than 40% in 6.5-8 hours at a dose of 5mg/
kg.[Conclusion]Monomeric Aβ levels in ISF can be altered,reflecting the dynamic equilibrium of Aβ forms in J20 mice.Acute administration of PER rapidly reduced ISF-Aβ levels in young J20 mice prior to Aβ deposition,indicating that this agent is a potential therapeutic materialto reduce future Aβ burden.
Pe-13-2
withdrawnPe-12-5
withdrawnpreplaquephaseofAPPswe/PS1dE9mice
○TaroSaito1,ShinHisahara1,KazukiYokokawa1,HiromiSuzuki1, TatsuoManabe1,AkihiroMatsumura1,SyuuichirouSuzuki1, TakashiMatsushita1,NaotoshiIwahara3,JunKawamata2, ShunShimohama1
1 Department of Neurology, Sapporo Medical University, Japan, 2 Department of Neurology, Kitasato University School of Medicine, 3 Boston University School of Medicine
[Objective]Alzheimer's disease （AD） is a common neurodegenerative disease that progressively impairs memory and cognition. Deposition of amyloid-β （A β） peptides is the most important pathophysiological hallmark of AD. Oxidative stress induced by generation of reactive oxygen species （ROS） is a prominent phenomenon in AD and known to occur early in the course of AD. Several reports suggest a relationship between change in redox status and AD pathology including progressive Aβ deposition, glial cell activation, and inflammation. Galantamine is an acetylcholinesterase inhibitor and has been reported to have an oxidative stress inhibitory function. [Methods]In the present study, galantamine was administered orally to AD model mice from before the appearance of Aβ plaques （preplaque phase）.
[Results] Administration of galantamine from the preplaque phase ameliorated memory decline in Morris water maze test and novel object recognition test. The redox status of the brain showed that galantamine treatment improved the unbalanced redox state.
Additionally, galantamine administration enhanced microglial function to promote A β clearance, reducing the Aβ-positive area in the cortex and amount of insoluble Aβ in the brain. In contrast, galantamine treatment from the preplaque phase suppressed the production of proinflammatory cytokines through neurotoxic microglial activity.
[Conslusions]Therefore, galantamine administration from the preplaque phase may have the potential of clinical application for the prevention of AD.
Pe-13-1
AcaseofAutosomalDominantSpinocerebellar AtaxiaPatientinDistrictHospital○BolortsetsegDavaasuren1,DorjkhandBaldorj2
1 Medical Center of Bayangol District, Mongolia, 2 International Parkinson and Movement Disorder Society
Here I present the case of a 45-year-old man, presenting with bilateral cerebellar signs and with history suggestive of an autosomal dominant pattern of inheritance.His older sister and maternal uncle, suggestive of autosomal dominant inheritance but they were not found to have genetic test. This case throws light on the probability of more such cases in the multi- ethnic society ofBayangoldistrict, which are not studied or reported till date. Key words: Autosomal dominant, ataxia, SCA, cerebellum In modern world, careful attention must be paid to clinical phenotype. Diverse rates of SCA have been observed since molecular testing became available over the past decade.
Worldwide, the most common SCA is SCA3, which together with SCA1, SCA2, SCA6 and SCA7 comprise 50% of all dominant ataxias. . In Asia, SCA 3 are most among amongst Chinese from China and Taiwan, SCA 2 was the most frequent hereditaryataxia （12.6%） and types 3 and 6 accounted for4.6% and 6.9% of ataxia patients, respectively in Korea. We need to use DNA sequencing technologies more accessible and multi religious pattern of society types SCA detect in our country.In our area when diagnostic modality is limited, physical examination, patient history, MRI supported be DNA sequencing technologies can control life of a SCA patient and improve quality of life whatever little bit . We might have to registers for patients.
一 般 演 題
ポ ス タ ー （ 英 語 ）
Pe-12-8
EffectivenessofgalantaminetreatmentfromPe-11-8
Transplantationofamnioticmesenchymalstemcellsamelioratesbraindamageaftercerebralischemia
○ShiroTakahashi1,2,ChikakoNito1,YukiSakamoto1,
MasafumiArakawa1,2,SatoshiSuda1,YukoNitahara-kasahara2,3,
TakashiOkada3,KazumiKimura1
1 Department of Neurology, Graduate School of Medicine, Nippon Medical School, Japan, 2 Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Nippon Medical School, Japan, 3 Department of Cell and Gene Therapy, Graduate School of Medicine, Nippon Medical School [Objective] Several studies have focused on cell therapies by using embryonic stem cells to prevent brain injury after ischemia. The transplantation of human amnion-derived mesenchymal stem cells （AMSCs） yielded positive therapeutic outcomes in various animal models of diseases. In this study, we investigated the effects of intravenous AMSC administration after transient middle cerebral artery occlusion
（MCAO） in rats. [Methods] Male SD rats underwent transient 90 min MCAO. 1×106 AMSCs or vehicle were administered just after reperfusion （n=5, each）. The infarct and edema volume were measured 24 h after reperfusion. Neurological performance and survival rate were evaluated on days 1, 7 and 28 after transient MCAO. [Results]
Transplanted AMSCs significantly reduced infarct and edema volume （p<0.05, p<0.01）
and reversed motor deficits at 24 h after reperfusion （abnormal posture; p<0.01, hemiparesis; p<0.0001）. Compared with the saline group, animal treated with AMSCs exhibited improved neurological performance in the Rota -Rod test at 28 days after transient MCAO （p<0.01）. 2 rats treated with vehicle were dead （survival rate:60%）
and all rats could survive in the AMSC-treated group. [Conclusions] The present study shows that administration of human AMSCs immediately after reperfusion improved ischemic damage, neurological function and survival rate in a rodent model of focal cerebral ischemia. These results suggest that transplanted AMSCs would induce neuroprotection and functional recovery after ischemia/reperfusion injury.
Pe-12-1
Clinicalcharacteristicsofemergencypatients withdementiainalocalclinic○KohTadokoro1,2,RyoSasaki1,2,YosukeWakutani2,YoshikiTakao1,
YoshioOmote1,MamiTakemoto1,NozomiHishikawa1,
YasuyukiOhta1,ToruYamashita1,KojiAbe1
1 Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan, 2 Department of Neurology, Kurashiki Heisei Hospital, Japan
[Objective] To clarify the clinical characteristics of emergency patients with dementia in a local clinic. [Methods] We retrospectively examined patients with dementia who visited our emergency clinic. Among 16,764 patients who visited our emergency clinic in 3 years from 2014 to 2017, we focused on 2,574 （15.4%） patients with dementia. [Results] The mean age of patients with dementia was 84.9 ± 0.1 years, which was much older than the age of the total emergency patients （58.1 ± 0.2 years）. The hospitalization rate was 54.9% for patients with dementia, which was more than double that of patients without dementia （23.3%; P < 0.01）, and was higher than that （44.3%） of patients who were aged 75 years old or older without dementia. Infection （42.4%） and falls
（20.9%） were the most common causes for emergency visits and hospitalization in the present study. Hospitalized patients with dementia spent a longer time in hospital for stroke （64.0 ± 5.3 days） and falls （51.9 ± 2.1 days） than those with those with infection, epilepsy, syncope, loss of consciousness, other causes
（P < 0.01）, or dehydration （P < 0.05）. [Conclusions] Emergency patients with dementia were commonly experienced in our clinic. These patients were older in age, had a higher hospitalization rate, and had a longer hospitalization, especially due to stroke and falls, than patients without dementia.
Pe-12-2
Tricetinaseffectiveantialzheimerspotentials throughforAChEandBChEenzymesinhibition○KanikaPatel,DineshKumarPatel
Sam Higginbottom University of Agriculture, Technology and Sciences, India
Objective: The most prevalent neurodegenerative disease is Alzheimer's disease （AD） and worldwide it is the most common cause of dementia. The aim of the present study is to identify phytoconstituents for the treatment of Alzheimer's disease through a AChE and BChE enzymes inhibition. Methods:
Various databases have been searched for the therapeutic potential of Tricetin in various animal models and in in-vitro study. All the data have been analyzed through various statistical methods to get proper correlation of Alzheimer's disease with acetylcholine level, oxidative stress, and inflammation. AChE and BChE inhibitory potential of Tricetin through in-silico molecular docking have been done to know their binding modes, drug likeness properties and inhibitory mechanisms. Results: Docking study results have confirmed that Tricetin have good affinity into AChE and BChE binding site. Consequently Tricetin reversibly inhibited AchE and BChE in a mixed-competitive manner. Glide Gscore and binding energies were calculated and found that a hydrophobic interaction of Tricetin with AChE and BuChE has been confirmed with low binding energies. Further In-vitro assays showed that Tricetin have better antioxidant potential which supports their possible role in Alzheimer's disease.
In-silico prediction of blood-brain barrier （BBB） permeation and ADMET properties of Tricetin was also reported in various databases. Conclusions:
This study could lead to the further development of potent acetylcholinesterase inhibitors for the treatment of Alzheimer's disease.
Pe-12-3
Acationicgalliumphthalocyanineinhibits amyloidbetapeptidefibrilformation○ShateraTabassum1,AbdullahM.Sheikh1,ShozoYano1,
TakahisaIkeue1,YoshieIto1,ShingoMitaki1,MakotoMichikawa2,
AtsushiNagai1
1 Shimane University, Japan, 2 Nagoya City University
Background: Amyloid β （Aβ） peptide deposition is considered as the main cause of Alzheimer's disease （AD）. Previously, we have found that a Zn containing neutral phthalocyanine （Zn-Pc） inhibits Aβ fibril formation.
Purpose: The purpose of this study is to investigate the effects of a cationic gallium containing Pc （GaCl-Pc） on Aβ fibril formation process. Methods and Result: Aβ fibril formation was induced by incubating synthetic A β peptides in fibril forming buffer, and the amount of fibril was evaluated by ThT fluorescence assay. GaCl-Pc dose-dependently inhibited both Aβ
1-40 and Aβ1-42 fibril formation. It mainly inhibited the elongation phase of A β1-42 fibril formation kinetics, but not the lag phase. Near infrared scanning result showed that GaCl-Pc had the ability to bind to Aβ1-42. But Western blotting results showed that it did not inhibit its oligomerization process. MTT assay demonstrated that GaCl-Pc did not show any toxicity in the culture of a neuronal cell line, rather it demonstrated protective effects on Aβ-induced toxicity. GaCl-Pc destabilized preformed Aβ1-42 fibrils dose dependently in vitro condition. Importantly, when incubated with brain slice culture （n=5） or non-fixed brain tissues （n=5） of APP transgenic AD mice （J20 strain）, GaCl-Pc decreased tissue Aβ level, as revealed by immunostaining. Conclusion:
Thus our result demonstrated that GaCl-Pc decreased Aβ aggregation and destabilized preformed fibril. Since cationic molecules show better ability to cross the blood brain barrier, cationic GaCl-Pc could be important for the therapy of AD.
Pe-12-4
NeuroprotectiveeffectsofGossypetininAlzheimer's disease:In-silicoandIn-vitroapproaches○DineshK.Patel,KanikaPatel
Department of Pharmaceutical Science, Shalom Institute of Health and Allied Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, India
Purpose: Gossypetin is a flavonoid which is basically flavone and found in hibiscus species. Acetylcholinestrase and butrylcholinesterase enzymes play an important role in the Alzheimers disease and inhibition of these enzymes are the key factors for the treatment of Alzhemers disease.Plant are valuable source of phytochemicals which can inhibit cholinestrase. Protective effects of gossypetin in the management of alzheimers disease have been investigated in the present work through inhibitory potential of gossypetin on cholinesterase.
Method: In order to understand the beneficial health aspect of gossypetin in brain related disorder, effect of gossypetin on cholinesterase enzymes have been investigated through In silico method. However present work also summarized the pharmacological properties of gossypetin with special reference to its effect on cholinesterase inhibitory potential. Results: From the data analysis it was found that gossypetin has antioxidant, antimutagenic, antiatherosclerotic, antimicrobial and cytoprotective properties. Docking study revealed the interaction of gossypetin with the pocket region of the cholinesterase enzymes. Further molecular docking study also revealed the probable mechanism of binding modes of inhibitors to cholinesterase.
Conclusion: These findings put more insights into understanding the interaction of gossypetin and cholinesterase enzymes. This work will be beneficial for the entire scientific person to find out more insights of gossypetin in alzheimers disease.