Investigation of the mechanism of ischemic brain injury in extremely preterm infants

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09723
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Keio University
• Principal Investigator: Deguchi Kimiko 慶應義塾大学, 医学部(信濃町), 講師(非常勤) (50227542)
• Co-Investigator(Kenkyū-buntansha): 久保 健一郎 慶應義塾大学, 医学部(信濃町), 講師 (20348791)
• Co-Investigator(Renkei-kenkyūsha): INOUE Ken 国立精神, 神経センター・神経研・疾病二部, 室長 (30392418)
• Research Collaborator: ISHII Kazuhiro
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 虚血 / 脳障害 / 神経細胞移動 / マウスモデル / 認知機能 / 大脳皮質 / 層構造 / 治療法開発

Outline of Final Research Achievements

Many extremely preterm infants (EPIs) subsequently develop cognitive impairment of unknown etiology. We observed fewer neural progenitors and larger numbers of ectopic neurons in the white matter (WM) of human EPI brains and hypothesized that EPIs develop cognitive dysfunction because of altered neuronal generation and migration. To test our hypothesis we produced ischemic brain damage in mouse embryos by occluding maternal uterine arteries. The mice showed decreased proliferation of neuronal progenitors, delayed neuronal migration, and ectopic neurons in the WM. Similar to human EPIs the surviving mice exhibited abnormal cognitive function. Maternal hypothermia during the arterial occlusion period mitigated the neurodevelopmental damage. These findings supported our hypothesis that altered neuronal generation and migration underlie the serious risk of subsequent cognitive impairment of EPIs.

Free Research Field

小児科科学、神経発生学