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Published on: August 15, 2012
Neuroprotective potential of molecular hydrogen against perinatal brain injury via suppression of activated microglia
Kenji Imai1, Tomomi Kotani1, Hiroyuki Tsuda1
1Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Insights
Molecular hydrogen (H2) shows promise in preventing perinatal brain injury caused by prenatal inflammation. This antioxidant and anti-inflammatory agent reduces inflammation, oxidative damage, and microglial activation in fetal brains.
Area of Science:
- Neuroscience
- Perinatal Medicine
- Molecular Biology
Background:
- Prenatal inflammation is linked to perinatal brain injury, leading to significant long-term child morbidity and mortality.
- Activated microglia play a key role in brain injury by releasing inflammatory cytokines and oxidative products.
- Understanding the pathogenesis of prenatal inflammation is crucial for developing new therapeutic interventions.
Purpose of the Study:
- To investigate the preventative potential of molecular hydrogen (H2) against inflammation-induced perinatal brain injury.
- To evaluate the effects of maternal administration of hydrogen water (HW) on fetal brain development in a mouse model.
- To elucidate the neuroprotective mechanisms of H2, particularly its interaction with microglia.
Main Methods:
- A mouse model was established by injecting pregnant ICR mice with lipopolysaccharide (LPS) on embryonic day 17.
- Maternal administration of hydrogen water (HW) was assessed for its effects on pups.
- Pro-inflammatory cytokine levels, oxidative damage, microglial activation, and reactive oxygen species (ROS) generation were measured in fetal brains and cultured cells.
Main Results:
- H2 significantly reduced LPS-induced pro-inflammatory cytokine expression, oxidative damage, and microglial activation in fetal brains.
- H2 prevented LPS- or cytokine-induced ROS generation by microglia and mitigated LPS-induced microglial neurotoxicity.
- Several molecules influenced by H2, involved in microglial activation pathways, were identified.
Conclusions:
- Molecular hydrogen (H2) demonstrates significant potential as a preventative therapeutic agent for inflammation-related perinatal brain injury.
- H2 exerts neuroprotection by inhibiting microglial activation, reducing oxidative stress, and modulating inflammatory pathways.
- Further research into H2's mechanisms could lead to novel strategies for protecting the developing brain.
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.
