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Pathophysiology of neurological disorders in preterm infants with a focus on cerebellar disorders and elucidation of the therapeutic mechanism of stem cell therapy.

Research Project

Project/Area Number 21K07794
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionNagoya University

Principal Investigator

Sato Yoshiaki  名古屋大学, 医学部附属病院, 病院准教授 (30435862)

Co-Investigator(Kenkyū-buntansha) 飛田 秀樹  名古屋市立大学, 医薬学総合研究院(医学), 教授 (00305525)
湯川 博  名古屋大学, 未来社会創造機構, 特任教授 (30634646)
小野田 淳人  山陽小野田市立山口東京理科大学, 薬学部, 助教 (70835389)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords超低出生体重児 / 慢性肺疾患 / 高酸素 / 小脳障害 / 小脳 / 周産期脳障害 / 発達障害 / 超低出生体重
Outline of Research at the Start

新生児医療の進歩により早産児の死亡率は大きく改善したが、神経学的障害を残す児の数は減っていない。これまで神経学的障害の原因として大脳病変が言われており広く研究されてきたが、小脳病変は着目されてこなかった。小脳病変の病理病態の解明が、早産児に生じる神経学障害を改善する新規治療法の開発に繋がると考え、本研究では、“早産児に伴う神経学的障害の克服”に対し、小脳障害に焦点を当て研究を行う。

Outline of Final Research Achievements

In this project, in a chronic lung disease (CLD) model that mimics the pathophysiology of hyperoxia exposure in preterm infants, we found behavioral abnormalities suggestive of motor deficits, cognitive memory impairment, and social deficits, as well as histological cerebellar lesions, including delayed cell migration of granule cells in the acute phase and reduced myelination and abnormal dendritic development of Purkinje cells in the chronic phase, were revealed. We showed that abnormal cerebellar function in preterm infants born prematurely when cerebellar development was at its peak might be caused by postnatal exposure to an environment different from that in utero (exposure to relatively high concentrations of oxygen), which might affect the neurological developmental outcome in preterm infants.

Academic Significance and Societal Importance of the Research Achievements

早産児における神経学的障害に関しては、未だ解決の糸口のない大きな課題であり、今まで主な研究対象となってきた大脳病変ではなく、小脳病変が神経学的発達予後に影響を及ぼす可能性を示すことができ、新たな治療戦略の礎となる。

Report

(2 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (7 results)

All 2024 2023

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 6 results)

  • [Journal Article] Total Hydrocortisone Dosage in the Neonatal Period May Be Related to Low Developmental Quotient in Extremely Low Birth Weight Infants: A Retrospective Cohort Study2024

    • Author(s)
      Taniguchi Akinobu、Nishida Kazuki、Suzuki Toshihiko、Kataoka Erina、Fujishiro Naozumi、Kato Eiko、Yamamoto Hikaru、Takemoto Koji、Ito Miharu、Hayashi Seiji、Sugiyama Yuichiro、Maeda Takashi、Takahashi Yoshiyuki、Sato Yoshiaki
    • Journal Title

      Neonatology

      Volume: 121 Issue: 2 Pages: 195-202

    • DOI

      10.1159/000534934

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Systemic administration of clinical-grade multilineage-differentiating stress-enduring cells ameliorates hypoxic?ischemic brain injury in neonatal rats2023

    • Author(s)
      Ueda Kazuto、Sato Yoshiaki、Shimizu Shinobu、Suzuki Toshihiko、Onoda Atsuto、Miura Ryosuke、Go Shoji、Mimatsu Haruka、Kitase Yuma、Yamashita Yuta、Irie Keiichi、Tsuji Masahiro、Mishima Kenichi、Mizuno Masaaki、Takahashi Yoshiyuki、Dezawa Mari、Hayakawa Masahiro
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 14958-14958

    • DOI

      10.1038/s41598-023-41026-3

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Various Organ Damages in Rats with Fetal Growth Restriction and Their Slight Attenuation by Bifidobacterium breve Supplementation2023

    • Author(s)
      Tsuji Masahiro、Tanaka Nao、Koike Hitomi、Sato Yoshiaki、Shimoyama Yoshie、Itoh Ayaka
    • Journal Title

      Life

      Volume: 13 Issue: 10 Pages: 2005-2005

    • DOI

      10.3390/life13102005

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Umbilical cord-derived mesenchymal stromal cell therapy to prevent the development of neurodevelopmental disorders related to low birth weight2023

    • Author(s)
      Tsuji Masahiro、Mukai Takeo、Sato Yoshiaki、Azuma Yasue、Yamamoto Saki、Cayetanot Florence、Bodineau Laurence、Onoda Atsuto、Nagamura-Inoue Tokiko、Coq Jacques-Olivier
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 3841-3857

    • DOI

      10.1038/s41598-023-30817-3

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Altered offspring neurodevelopment in an L-NAME-induced preeclampsia rat model2023

    • Author(s)
      Nakamura Noriyuki、Ushida Takafumi、Onoda Atsuto、Ueda Kazuto、Miura Ryosuke、Suzuki Toshihiko、Katsuki Satoru、Mizutani Hidesuke、Yoshida Kosuke、Tano Sho、Iitani Yukako、Imai Kenji、Hayakawa Masahiro、Kajiyama Hiroaki、Sato Yoshiaki、Kotani Tomomi
    • Journal Title

      Frontiers in Pediatrics

      Volume: 11 Pages: 1168173-1168173

    • DOI

      10.3389/fped.2023.1168173

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dedifferentiated fat cells administration ameliorates abnormal expressions of fatty acids metabolism-related protein expressions and intestinal tissue damage in experimental necrotizing enterocolitis2023

    • Author(s)
      Mimatsu Haruka、Onoda Atsuto、Kazama Tomohiko、Nishijima Koji、Shimoyama Yoshie、Go Shoji、Ueda Kazuto、Takahashi Yoshiyuki、Matsumoto Taro、Hayakawa Masahiro、Sato Yoshiaki
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 8266-8266

    • DOI

      10.1038/s41598-023-34156-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fetal growth restriction followed by early catch-up growth impairs pancreatic islet morphology in male rats2023

    • Author(s)
      Jabary Mahboba、Onoda Atsuto、Kitase Yuma、Ueda Kazuto、Mimatsu Haruka、Go Shoji、Miura Ryosuke、Tsuji Masahiro、Takahashi Yoshiyuki、Hayakawa Masahiro、Sato Yoshiaki
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 2732-2732

    • DOI

      10.1038/s41598-023-28584-2

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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