Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model

Abstract

The aim of the present study was to investigate long-term outcomes of the offspring in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) model and the effect of maternal molecular hydrogen (H2) administration. We have previously demonstrated in the MIA mouse model that maternal administration of H2 attenuates oxidative damage and neuroinflammation, including induced pro-inflammatory cytokines and microglial activation, in the fetal brain. Short-term memory, sociability and social novelty, and sensorimotor gating were evaluated using the Y-maze, three-chamber, and prepulse inhibition (PPI) tests, respectively, at postnatal 3 or 4 weeks. The number of neurons and oligodendrocytes was also analyzed at postnatal 5 weeks by immunohistochemical analysis. Offspring of the LPS-exposed dams showed deficits in short-term memory and social interaction, following neuronal and oligodendrocytic loss in the amygdala and cortex. Maternal H2 administration markedly attenuated these LPS-induced abnormalities. Moreover, we evaluated the effect of H2 on LPS-induced astrocytic activation, both in vivo and in vitro. The number of activated astrocytes with hypertrophic morphology was increased in LPS-exposed offspring, but decreased in the offspring of H2-administered dams. In primary cultured astrocytes, LPS-induced pro-inflammatory cytokines were attenuated by H2 administration. Overall, these findings indicate that maternal H2 administration exerts neuroprotective effects and ameliorates MIA-induced neurodevelopmental deficits of offspring later in life.

Hydrogen: A Novel Option in Human Disease Treatment

“…In addition, hydrogen can also protect against spinal cord injury and a variety of brain injuries caused by ischemia, hypoxia, trauma, and hemorrhage. A clinical study of patients suffering from cerebral infarction reported that hydrogen inhalation improved imaging results, National Institutes of Health Stroke Scale scores used to quantify the severity of stroke, and physical therapy evaluations based on the Barthel Index [ 82 ]. A rat model of subarachnoid hemorrhage revealed the influence of hydrogen in lessening neurological deficits [ 83 ] and endothelial cell injury [ 84 ].…”

Prenatal Molecular Hydrogen Administration Ameliorates Several Findings in Nitrofen-Induced Congenital Diaphragmatic Hernia

“…Its concentration was approximately 0.6 ppm. HW had a content of >0.4 mM H 2 , as reported previously [15][16][17][18][49][50][51]. Anti-PDGFRβ antibody [Y92] (ab32570, lot no.…”

“…The long-term safety of inhaled hydrogen gas in mice has already been reported [48]. Although several therapeutic and preventive effects for various obstetric diseases such as preterm labor [49], preeclampsia [50], fetal brain injury [16,51], and fetal lung injury [15] have been reported, these studies did not report short-term adverse effects. Fourth, it is already known that this method of prenatal H 2 administration increases the hydrogen concentration in fetal lungs [15].…”

“…Subsequently, HW was provided ad libitum, and the rats drank approximately 120 mL/kg of HW per day, as previously described [15]. HW was aliquoted into glass drinking bottles, which were changed every 24 h to prevent H2 degassing and air refilling, as previously reported [15][16][17][18][49][50][51]. Figure 6.…”

Ex vivo 1H-MRS brain metabolic profiling in a two-hit model of schizophrenia-related alterations: effects of prenatal immune activation and peripubertal stress

“…Poly I:C (see Meyer 2014 for a review) and also with LPS exposure (Fortier et al, 2007;Romero et al, 2010;Simões et al, 2018;Swanepoel et al, 2018;Waterhouse et al, 2018;Wischhof et al, 2015) although some variables such as the species used (Imai et al, 2018), the prenatal period at which exposure occurs (Waterhouse et al, 2018) Figure 1, PUS seems to be counteracting LPS effects to some extent. Therefore, a stronger effect of LPS exposure might be needed to obtain a main effect of the maternal immune activation or an interaction between both factors.…”