An approach to pathological analysis of fetal and neonatal brain damage from the viewpoint of brain development (six layers of cerebrum)

• Project/Area Number: 15K10695
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kawasaki Medical School
• Principal Investigator: SHIMOYA KOICHIRO 川崎医科大学, 医学部, 教授 (40291950)
• Co-Investigator(Kenkyū-buntansha): 潮田 至央 川崎医科大学, 医学部, 講師 (40454821) ; 村田 卓也 川崎医科大学, 医学部, 講師 (20714207) ; 冨松 拓治 大阪大学, 医学系研究科, 准教授 (30346209) ; 中井 祐一郎 川崎医科大学, 医学部, 准教授 (50271193) ; 中村 隆文 川崎医科大学, 医学部, 教授 (20303969) ; 村田 晋 山口大学, 医学部附属病院, 助教 (00420521) ; 石田 剛 川崎医科大学, 医学部, 講師 (90509225)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 脳障害 / 大脳6層構造 / 子宮内感染 / 母体ストレス / 新生児脳障害 / 脳性麻痺 / 早産 / サイトカイン / 神経前駆細胞 / 胎児脳障害

Outline of Final Research Achievements

Although advances in perinatal care have dramatically improved the prognosis of mothers and infants, neonatal brain damage is still a major issue in perinatology. In this study, we established a system for quantitative analysis of cerebral six-layer structure and cell migration using immunohistological analysis of neonatal the mouse cerebrum. A model of intrauterine infection and/or preterm birth by LPS, which is a bacterial cell component, into the abdominal cavity and the amniotic fluid of pregnant mice was constructed, and immunohistological analysis of the neonatal mouse cerebrum was performed. We revealed the disorder of the six-layer structure and the movement of cerebrum cells. Impairment of mobility was recognized, and there was a possibility that it might be a factor of postnatal brain damage. In addition, the examination using clinical samples showed that maternal stress may change maternal behavior by evaluation with maternal stress markers.

Academic Significance and Societal Importance of the Research Achievements

周産期医療領域において最大の命題で有る胎児・新生児脳障害について大脳皮質の発生に着目して病態形成の解明に結びつけようとする研究であり、早産・子宮内感染が大脳皮質の6層構造構築に影響を及ぼす点から発生学的視点で脳障害および機能障害の予防および制御の可能性があることを明らかにした意義がある。さらに妊娠中および産褥期の母体ストレスが母性行動に影響することから児の発達にも影響を及ぼすことは考えられ、妊娠・産褥期の母体のメンタルケアの重要性を明らかにした点にも意義がある。

Research Products

• [Journal Article] Unresponsiveness to oxytocin due to an extremely thin uterine wall in a pregnant woman with systemic lupus erythematosus and Sjögren's syndrome. (2018)
  • Author(s): Tomimatsu T, Hazama Y, Takeuchi M, Kimura T, Shimoya K.
  • Journal Title: Unresponsiveness to oxytocin due to an extremely thin uterine wall in a pregnant woman with systemic lupus erythematosus and Sjögren's syndrome. Volume: Feb;38(2) Pages: 276-278
  • Peer Reviewed
• [Journal Article] Vasohibin-1 Is a Poor Prognostic Factor of Ovarian Carcinoma (2017)
  • Author(s): Sano R, Kanomata N, Suzuki S, Shimoya K, Sato Y, Moriya T, Shiota M.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 243 Issue: 2 Pages: 107-114
  • DOI: 10.1620/tjem.243.107
  • NAID: 130006178275
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed / Open Access
• [Journal Article] The Analysis of Cell Cycle-related Proteins in Ovarian Clear Cell Carcinoma Versus High-grade Serous Carcinoma. (2017)
  • Author(s): Hazama Y, Moriya T, Sugihara M, Sano R, Shiota M, Nakamura T, Shimoya K.
  • Journal Title: Int J Gynecol Pathol. Volume: Oct 10 Issue: 6 Pages: 516-524
  • DOI: 10.1097/pgp.0000000000000461
  • Peer Reviewed
• [Journal Article] Maternal Depression and Mother-to-Infant Bonding: The Association of Delivery Mode, General Health and Stress Markers (2017)
  • Author(s): Mihyon Song, Hiroshi Ishii, Masahiro Toda, Takuji Tomimatsu, Hironobu Katsuyama, Yuichiro Nakai, Koichiro Shimoya
  • Journal Title: Open Journal of Obstetrics and Gynecology Volume: 7 Issue: 02 Pages: 155-166
  • DOI: 10.4236/ojog.2017.72017
  • Peer Reviewed / Open Access
• [Journal Article] Guillain-Barré syndrome after trivalent influenza vaccination during pregnancy. (2016)
  • Author(s): Tomimatsu T, Sugihara M, Nagai T, Sunada Y, Kimura T, Shimoya K.
  • Journal Title: Eur J Obstet Gynecol Reprod Biol. Volume: 201 Pages: 225-226
  • DOI: 10.1016/j.ejogrb.2016.03.031
  • Peer Reviewed
• [Journal Article] Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma. (2016)
  • Author(s): Matsuo K, Takazawa Y, Ross MS, Elishaev E, Podzielinski I, Yunokawa M, Sheridan TB, Bush SH, Klobocista MM, Blake EA, Takano T, Matsuzaki S, Baba T, et al.
  • Journal Title: Ann Oncol. Volume: 27 Issue: 7 Pages: 1257-1266
  • DOI: 10.1093/annonc/mdw161
  • Peer Reviewed / Open Access / Int'l Joint Research