Maternal molecular hydrogen administration on lipopolysaccharide-induced mouse fetal brain injury

  • Nakano Tomoko
    Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine
  • Kotani Tomomi
    Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine
  • Mano Yukio
    Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine
  • Tsuda Hiroyuki
    Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine
  • Imai Kenji
    Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine
  • Ushida Takafumi
    Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine
  • Li Hua
    Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine
  • Miki Rika
    Bio-database Institute of Reproductive and Developmental Medicine, Nagoya University Graduate School of Medicine
  • Sumigama Seiji
    Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine
  • Sato Yoshiaki
    Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital
  • Iwase Akira
    Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine
  • Hirakawa Akihiro
    Biostatistics Section, Center for Advanced Medicine and Clinical Research Cancer, Nagoya University Graduate School of Medicine
  • Asai Masato
    Department of Pathology, Nagoya University Graduate School of Medicine
  • Toyokuni Shinya
    Pathology and Biological Responses, Nagoya University Graduate School of Medicine
  • Kikkawa Fumitaka
    Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine

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Abstract

Fetal brain injury is often related to prenatal inflammation; however, there is a lack of effective therapy. Recently, molecular hydrogen (H2), a specific antioxidant to hydroxyl radical and peroxynitrite, has been reported to have anti-inflammatory properties. The aim of this study was to investigate whether maternal H2 administration could protect the fetal brain against inflammation. Pregnant C3H/HeN mice received an intraperitoneal injection of lipopolysaccharide (LPS) on gestational day 15.5 and were provided with H2 water for 24 h prior to LPS injection. Pup brain samples were collected on gestational day 16.5, and the levels of apoptosis and oxidative damage were evaluated using immunohistochemistry. Interleukin-6 (IL-6) levels were examined using real-time PCR. The levels of apoptosis and oxidative damage, as well as the levels of IL-6 mRNA, increased significantly when the mother was injected with LPS than that in the control group. However, these levels were significantly reduced when H2 was administered prior to the LPS-injection. Our results suggest that LPS-induced apoptosis, oxidative damage and inflammation in the fetal brain were ameliorated by maternal H2 administration. Antenatal H2 administration might protect the premature brain against maternal inflammation.

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