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

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.

Effect of molecular hydrogen on uterine inflammation during preterm labour

“…Notably, H 2 was demonstrated to exert anti-oxidative and anti-inflammatory effects in foetal organs following intraperitoneal injection of LPS in rodent models (7)(8)(9). It is established that preterm labour is associated with inflammation, but the associated mechanism is not fully understood.…”

“…Our previous reports demonstrated that may H 2 prevent foetal inflammation and oxidative damage (7)(8)(9), and compared to the effects of H 2 on foetal damage, its effects on preterm labour were limited. These findings suggest that H 2 pretreatment may be appropriate for preventing foetal injury from maternal inflammation at preterm labour, but has low potential to inhibit preterm birth.…”

“…Finally, the slides were counterstained with Meyer's haematoxylin at room temperature for 30 sec. For the quantification of immunostaining, the intensity was evaluated as intensity score (IS), as previously reported (9). Two independent examiners determined the IS from three segments per slide at x400 magnification with an Axio Imager A1 (Carl Zeiss Microscopy Co., Ltd., Tokyo, Japan) using a 4-point system: 0, 1, 2 and 3 (for no, light, medium and dark staining, respectively); the mean score from the two examiners was used.…”

“…Previous reports by our group demonstrated that the maternal administration of molecular hydrogen (H 2 ), known Effect of molecular hydrogen on uterine inflammation during preterm labour for its anti-oxidative and anti-inflammatory effects (6), ameliorated damage in foetal pulmonary and brain tissue caused by intrauterine inflammation in lipopolysaccharide (LPS)-induced rodent models (7)(8)(9). There are more than 300 reports outlining the utility of H 2 for the prevention or improvement of various diseases including inflammatory disease (6).…”

Molecular Hydrogen as a Neuroprotective Agent

“…reported that maternal administration of HW ameliorates mouse fetal brain injury induced with maternal exposure to LPS. Expression of pro-inflammatory cytokines, oxidative damage, and microglial activation caused by intrauterine inflammation are suppressed by HW [ 78 , 79 ]. These data suggest that prenatal administration of H 2 can be an effective therapeutic approach for FIRS.…”