Neuroprotective potential of molecular hydrogen against perinatal brain injury via suppression of activated microglia.

Abstract

Exposure to inflammation in utero is related to perinatal brain injury, which is itself associated with high rates of long-term morbidity and mortality in children. Novel therapeutic interventions during the perinatal period are required to prevent inflammation, but its pathogenesis is incompletely understood. Activated microglia are known to play a central role in brain injury by producing a variety of pro-inflammatory cytokines and releasing oxidative products. The study is aimed to investigate the preventative potential of molecular hydrogen (H2), which is an antioxidant and anti-inflammatory agent without mutagenicity. Pregnant ICR mice were injected with lipopolysaccharide (LPS) intraperitoneally on embryonic day 17 to create a model of perinatal brain injury caused by prenatal inflammation. In this model, the effect of maternal administration of hydrogen water (HW) on pups was also evaluated. The levels of pro-inflammatory cytokines, oxidative damage and activation of microglia were determined in the fetal brains. H2 reduced the LPS-induced expression of pro-inflammatory cytokines, oxidative damage and microglial activation in the fetal brains. Next, we investigated how H2 contributes to neuroprotection, focusing on microglia, using primary cultured microglia and neurons. H2 prevented LPS- or cytokine-induced generation of reactive oxidative species by microglia and reduced LPS-induced microglial neurotoxicity. Finally, we identified several molecules influenced by H2, involved in the process of activating microglia. These results suggested that H2 holds promise for the prevention of inflammation related to perinatal brain injury.

• Authors: Kenji Imai, Tomomi Kotani, Hiroyuki Tsuda, Yukio Mano, Tomoko Nakano, Takafumi Ushida, Hua Li, Rika Miki, Seiji Sumigama, Akira Iwase, Akihiro Hirakawa, Kinji Ohno, Shinya Toyokuni, Hideyuki Takeuchi, Tetsuya Mizuno, Akio Suzumura, Fumitaka Kikkawa
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 91 Pg. 154-63 (Feb 2016) ISSN: 1873-4596 [Electronic] United States
• PMID: 26709014 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Lipopolysaccharides
• Neuroprotective Agents
• Reactive Oxygen Species
• Hydrogen

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Brain (drug effects, immunology, pathology)
• Brain Injuries (etiology, immunology, prevention & control)
• Cells, Cultured
• Cytokines (metabolism)
• Female
• Hydrogen (pharmacology)
• Lipopolysaccharides (pharmacology)
• Mice, Inbred ICR
• Microglia (drug effects, physiology)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress
• Pregnancy
• Pregnancy Complications (immunology, prevention & control)
• Reactive Oxygen Species (metabolism)