Development of non-human primate models to study neonatal HIE in regenerative medicine approach

• Project/Area Number: 15K15404
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Saitama Medical University
• Principal Investigator: Yamanouchi hideo 埼玉医科大学, 医学部, 教授 (10250226)
• Co-Investigator(Kenkyū-buntansha): 小柴 満美子 埼玉医科大学, 医学部, 客員准教授 (90415571)
• Co-Investigator(Renkei-kenkyūsha): SUGE Rie 埼玉医科大学, 医学部, 講師 (10342685) ; KATO Hidemasa 埼玉医科大学, 医学部, 准教授 (50292123)
• Research Collaborator: KOMURA Makoto 埼玉医科大学, 医学部, 教授 (10422289) ; NISHIMURA Kunihiro 埼玉医科大学, 医学部, 研究員 ; OZAWA Shimpei 埼玉医科大学, 医学部, 研究員 ; YODA Mayuko 埼玉医科大学, 短期大学, 助教 ; KARINO Genta 埼玉医科大学, 医学部, 特別研究生 ; KOMURA Makoto 埼玉医科大学, 医学部, 教授 (50195468) ; KAKEI Hiroko 埼玉医科大学, 医学部, 助教 (20573877) ; SAKURAI Hayato 埼玉医科大学, 医学部, 助教 (40751938)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 神経行動学 / 抗重力運動発達 / 補償生理基盤 / 低酸素暴露病態 / 霊長類モデル / 病態生理 / 血中酸素飽和度 / 脈拍 / 体温 / 補償 / 神経機能発達診断法 / 抗重力適応機能試験 / 神経科学 / 移植・再生医療 / 生理学 / 認知心理学

Outline of Final Research Achievements

Neurologic sequelae of neonatal hypoxic ischemic encephalopathy (HIE) supposedly includes cerebral palsy, which is extrapyramidal symptoms due to occurrence of respiratory and circulatory insufficiency in the perinatal period. To study HIE preclinically, we aimed to develop the non-human primate model of common marmoset.
A test system was designed and evaluated to simulate hypoxic environmentally exposed similarly to supposed situation with suppression of oxygen circulation under the other factors sufficient. Two primate groups were compared about the oxygen regulation to induce hypoxic and normal conditions. The results in the acute phase experiments with five as hypoxic and four as control groups suggested some "compensation-like" physical mechanism at blood oxygen saturation appropriately 20%. The acutely recovered infants from low oxygen exposure tended to view and behave differently in anti-gravity motion tests. This proposed model shows possibility for the furthermore studies.

Research Products

• [Int'l Joint Research] Renne大学(フランス)
• [Int'l Joint Research] ZENREI研究所(米国)
• [Int'l Joint Research] Institute of Translational Biomedicine(中国)
• [Journal Article] Psycho-Cognitive Intervention for ASD from Cross-Species Behavioral Analyses of Infants, Chicks and Common Marmosets. (2016)
  • Author(s): Koshiba M, Karino G, Mimura K, Nakamura S, Yui K, Kunikata T, Yamanouchi H
  • Journal Title: CNS & Neurol Disorders - Drug Targets Volume: 15(5) Issue: 5 Pages: 578-586
  • DOI: 10.2174/1871527315666160413121613
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Improving treatment of neurodevelopmental disorders: recommendations based on preclinical studies. (2016)
  • Author(s): Homberg JR, Kyzar EJ, Nguyen M, Norton WH, Pittman J, Poudel MK, Gaikwad S, Nakamura S, Koshiba M, Yamanouchi H, Scattoni ML, Ullman JF, Diamond DM, Kaluyeva AA, Parker MO, Klimenko VM, Apryatin SA, Brown RE, Song C, Gainetdinov RR, Gottesman II, Kalueff AV.
  • Journal Title: Expert Opin Drug Discov. Volume: 65 Issue: 1 Pages: 578-86
  • DOI: 10.1517/17460441.2016.1115834
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Deployment and problems after the "Joint recommendations on sedation during MRI examination" (2016)
  • Author(s): Korematsu S, Yamanouchi H.
  • Journal Title: No To Hattatsu Volume: 48 Pages: 107-110
  • NAID: 130005140045
  • Peer Reviewed
• [Journal Article] Successful treatment with chloramphenicol in four pediatric cases of intractable bacterial meningitis. (2016)
  • Author(s): Morita K, Abe Y, Itano A, Musha I, Koga T, Yamazaki T, Yamanouchi H.
  • Journal Title: No To Hattatsu Volume: 48(1) Pages: 29-33
  • NAID: 130005140037
  • Peer Reviewed
• [Journal Article] Manifestations and characteristics of congenital adrenal hyperplasia-associated encephalopathy. (2016)
  • Author(s): Abe Y, Sakai T, Okumura A, Akaboshi S, Fukuda M, Haginoya K, Hamano SI, Hirano K, Kikuchi K, Kubota M, Lee S, Maegaki Y, Sanefuji M, Shimozato S, Suzuki M, Suzuki Y, Takahashi M, Watanabe K, Mizuguchi M, Yamanouchi H.
  • Journal Title: Brain and Development Volume: 38 Issue: 7 Pages: 638-647
  • DOI: 10.1016/j.braindev.2016.01.007
  • Peer Reviewed
• [Journal Article] Psycho-Cognitive Intervention for ASD from Cross-Species Behavioral Analyses of Infants, Chicks and Common Marmosets. (2016)
  • Author(s): Koshiba M, Karino G, Mimura K, Nakamura S, Yui K, Kunikata T, Yamanouchi H.
  • Journal Title: CNS Neurol Disord Drug Targets. Volume: 15(5) Pages: 11-25
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Chloramphenicolが著効した小児難治性細菌性髄膜炎の4例. (2016)
  • Author(s): 森田 佳代, 阿部 裕一, 板野 篤志, 武者 育麻, 古賀 健史, 山崎 太郎, 山内 秀雄
  • Journal Title: 脳と発達 Volume: 48 Pages: 29-33
  • NAID: 130005140037
  • Peer Reviewed
• [Journal Article] 「MRI検査時の鎮静に関する共同提言」からの発展と課題． (2016)
  • Author(s): 是松聖悟、山内秀雄．
  • Journal Title: 脳と発達 Volume: 48 Pages: 107-110
  • NAID: 130005140045
  • Peer Reviewed
• [Journal Article] Understanding autism and other neurodevelopmental disorders through experimental translational neurobehavioral models. (2015)
  • Author(s): Homberg JR, Kyzar EJ, Nguyen M, Norton WH, Pittman J, Poudel MK, Gaikwad S, Nakamura S, Koshiba M, Yamanouchi H, Scattoni ML, Ullman JF, Diamond DM, Kaluyeva AA, Parker MO, Klimenko VM, Apryatin SA, Brown RE, Song C, Gainetdinov RR, Gottesman II, Kalueff AV.
  • Journal Title: Neurosci Biobehav Rev Volume: 65 Pages: 292-312
  • DOI: 10.1016/j.neubiorev.2016.03.013
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Generalized seizure with falling and unresponsive staring provoked by somatosensory stimulation: a video-EEG study. (2015)
  • Author(s): Suzuki S, Sassa K, Abe Y, Yamanouchi H.Generalized seizure with falling and unresponsive staring provoked by somatosensory stimulation: a video-EEG study.
  • Journal Title: Epileptic Disord Volume: 17 Issue: 3 Pages: 336-339
  • DOI: 10.1684/epd.2015.0761
  • Peer Reviewed
• [Journal Article] Early-infant diagnostic predictors of the neuro-behavioral development after neonatal care. (2015)
  • Author(s): Koshiba M, Kakei H, Honda M, Karino G, Niitsu M, Miyaji T, Kishino H, Nakamura S, Kunikata T, Yamanouchi H.
  • Journal Title: Behav Brain Res Volume: 276 Issue: 1 Pages: 143-150
  • DOI: 10.1016/j.braindev.2015.04.009
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Characteristic MRI features of chronic inflammatory demyelinating polyradiculoneuropathy. (2015)
  • Author(s): Abe Y, Terashima H, Hoshino H, Sassa K, Sakai T, Ohtake A, Kubota M, Yamanouchi H.
  • Journal Title: Brain Dev Volume: 18 Issue: 9 Pages: 1883-1888
  • DOI: 10.1016/j.braindev.2015.01.006
  • Peer Reviewed
• [Journal Article] Susceptible period of socio-emotional development affected by constant exposure to daylight. (2015)
  • Author(s): Koshiba M, Senoo A, Karino G, Ozawa S, Tanaka I, Honda Y, Usui S, Kodama T, Mimura K, Nakamura S, Kunikata T, Yamanouchi H, Tokuno H.
  • Journal Title: Neuroscience Research Volume: 93 Pages: 91-98
  • DOI: 10.1016/j.neures.2014.09.011
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Potential of a smartphone as a stress-free sensor of daily human behaviour. (2015)
  • Author(s): Mimura K, Kishino H, Karino G, Nitta E, Senoo A, Ikegami K, Kunikata T, Yamanouchi H, Nakamura S, Sato K, Koshiba M.
  • Journal Title: Behavioral Brain Research Volume: 1 Pages: 181-189
  • DOI: 10.1016/j.bbr.2014.06.007
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] マイコプラズマ肺炎の難治化予測因子. (2015)
  • Author(s): 岡野 翼,阿部 裕一, 荒尾 正人, 山崎 太郎, 荒木 隆一郎, 山内 秀雄, 徳山 研一, 大竹 明, 雨宮 伸.
  • Journal Title: 日本小児科学会雑誌 Volume: 119 Pages: 825-830
  • Peer Reviewed
• [Presentation] International symposium on acute encephalopathy in infancy and its related disorders. (2016)
  • Author(s): Hideo Yamanouchi
  • Organizer: The 18th annual meeting of infantile seizure society
  • Place of Presentation: 一橋会館、東京
  • Year and Date: 2016-07-01
  • Int'l Joint Research / Invited
• [Presentation] Interdisciplinary environmentology for next innovative generation to nurture proactive emotion, considering age-dependent mechanisms (2016)
  • Author(s): Mamiko Koshiba
  • Organizer: International Conference Innovative Application Research and Education
  • Place of Presentation: Chunboku University, Korea
  • Int'l Joint Research
• [Presentation] 衣食住・社会環境と神経系情報を包括視する発達診断および療育への可能性 (2016)
  • Author(s): 小柴満美子，筧 紘子，櫻井隼人，本多正和，森田佳代，小澤晋平，西村邦弘，中村 俊， 新津 守，國方徹也，山内秀雄
  • Organizer: 第58回日本小児神経学会学術集会シンポジウム
  • Place of Presentation: 京王プラザホテル、新宿
  • Invited
• [Presentation] Experimental animal health science and psychology leads active designs of next generation technology (2016)
  • Author(s): Mamiko Koshiba
  • Organizer: The 7th Regional “Stress and Behavior” ISBS Conference
  • Place of Presentation: 東京都市大学、横浜
  • Int'l Joint Research / Invited
• [Presentation] Aucte encephalopathy in infancy and its related disorders. (2016)
  • Author(s): Hideo Yamanouchi
  • Organizer: The 8th international resional (Asia) ISBS neruosicence and biological psychiatry “stress and behavior” conference, The international stress and behavior society.
  • Place of Presentation: 東京都市大学、横浜
  • Int'l Joint Research / Invited
• [Presentation] 小児期発症のてんかん症例に対するレベチラセタム及びラモトリギンの単剤・併用療法に関する検討． (2015)
  • Author(s): 阿部 裕一, 颯佐 かおり, 山内 秀雄．
  • Organizer: 第49回日本てんかん学会学術集会
  • Place of Presentation: 長崎
  • Year and Date: 2015-10-30
  • Invited
• [Presentation] tonic spasms時に脱力する筋電図を認めた点頭てんかんの1例． (2015)
  • Author(s): 颯佐 かおり(埼玉医科大学 小児科), 阿部 裕一, 山内 秀雄．
  • Organizer: 第49回日本てんかん学会学術集会
  • Place of Presentation: 長崎
  • Year and Date: 2015-10-30
  • Invited
• [Presentation] 非鎮静下撮影による新生児・脳MRI撮像法(T1、T2強調およびFA-map画像)． (2015)
  • Author(s): 櫻井 隼人, 筧 紘子, 戸田 紘一, 山内 秀雄, 國方 徹也．
  • Organizer: 第60回日本新生児成育医学会
  • Place of Presentation: 盛岡
  • Year and Date: 2015-10-23
  • Invited
• [Presentation] 脳性麻痺児に対するA型ボツリヌス毒素(Botulinum Toxin:BoNT)製剤の使用経験． (2015)
  • Author(s): 本多 正和, 櫻井 隼人, 筧 紘子, 國方 徹也, 山内 秀雄．
  • Organizer: 第60回日本新生児成育医学会
  • Place of Presentation: 盛岡
  • Year and Date: 2015-10-23
  • Invited
• [Presentation] 小児急性脳症の脳低温療法を施行した8例の後方視的検討. (2015)
  • Author(s): 颯佐 かおり, 南川 優輝, 阿部 裕一, 山内 秀雄.
  • Organizer: 第57回日本小児神経学会
  • Place of Presentation: 大阪
  • Year and Date: 2015-05-28
• [Presentation] 結節性硬化症の治療 これまでとこれから (2015)
  • Author(s): 山内 秀雄．
  • Organizer: 第57回日本小児神経学会
  • Place of Presentation: 大阪
  • Year and Date: 2015-05-28
  • Invited
• [Presentation] 急性脳症の経過中に中枢性尿崩症(CDI)と中枢性塩喪失症候群(CSWS)を合併した幼児の1例． (2015)
  • Author(s): 南川 優輝, 阿部 裕一, 颯佐 かおり, 古賀 健史, 山内 秀雄．
  • Organizer: 第57回日本小児神経学会
  • Place of Presentation: 大阪
  • Year and Date: 2015-05-28
  • Invited
• [Presentation] MRI共同提言の実現に向けて Sedation Essence in Children Under Regulated Environmentコース． (2015)
  • Author(s): 山中 岳, 井上 信明, 久我 修二, 草川 功, 阪井 裕一, 山内 秀雄．
  • Organizer: 第57回日本小児神経学会
  • Place of Presentation: 大阪
  • Year and Date: 2015-05-28
  • Invited
• [Presentation] MRI検査のための鎮静に関する実態調査． (2015)
  • Author(s): 三牧 正和, 山中 岳, 是松 聖悟, 山内 秀雄.
  • Organizer: 第57回日本小児神経学会
  • Place of Presentation: 大阪
  • Year and Date: 2015-05-28
  • Invited
• [Book] こどもの神経疾患の診かた (2016)
  • Author(s): 新島新一、山本仁、山内秀雄
  • Total Pages: 246
  • Publisher: 医学書院
• [Funded Workshop] The 7th Regional “Stress and Behavior” ISBS Conference, Yokohama, Japan (2016)
  • Place of Presentation: 東京都市大学、横浜
  • Year and Date: 2016-07-23
• [Funded Workshop] The 18th Annual Meeting of Infantile Seizure Society International Symposium on Acute Encephalopathy in Infancy and Its related Disorders. (2016)
  • Place of Presentation: 一橋会館、竹橋
  • Year and Date: 2016-07-01
• [Funded Workshop] 国際行動ストレス学会 (2015)
  • Place of Presentation: 神戸大学
  • Year and Date: 2015-07-26