Reactive oxygen species (ROS)-mediated oxidative stress plays a key role in the pathogenesis of central nervous system diseases, including vascular dementia (VaD). Thus, scientific attention has been given to the uptake of molecular hydrogen (H₂), a...
Reactive oxygen species (ROS)-mediated oxidative stress plays a key role in the pathogenesis of central nervous system diseases, including vascular dementia (VaD). Thus, scientific attention has been given to the uptake of molecular hydrogen (H₂), a powerful ROS scavenger that is abundant in nature, as a potential therapeutic candidate. Among the methods to supply H₂, we selected an oral supplement of magnesium hydride (MgH₂) and investigated its therapeutic role in cognitive impairment and hippocampal neuronal death associated with VaD. Sprague Dawley rats were randomly divided into 4 groups (n of each=8) and subjected to different conditions: SO, a group with vehicle and sham-operation; VEH, a group with a vehicle and 2VO/H (2 vessel occlusion and hypovolemia, used as a surgical model of VaD); MH-L, a group with low dose (5 mg/kg) of MgH₂ and 2VO/H; and MH-H, a group with high dose (15 mg/kg) of MgH₂ and 2VO/H. MgH₂ or vehicle was administered via an intragastric route for 14 days before the operation. Subsequently, the memory performances of rats were tested using three behavior tests, i.e., Y-maze-, Barnes maze-, and passive avoidance tests (PAT). On postoperative day 8, the number of viable neurons in the hippocampal Cornu Ammonis (CA) 1 region was measured. The results of behavioral tests revealed that memory performance was significantly hampered in the VEH group when compared with the SO group; however, the extent of the impairment was markedly diminished in the MH-L and MH-H groups. While the number of pyramidal neurons in hippocampal CA1 was largely reduced in the VEH group when compared with the SO group, this reduction was significantly attenuated in the MH-L and MH-H groups. The effects of MgH₂ were dose-dependent in PAT and histologic experiments. These results suggest that MgH₂ supplementation can attenuate cognitive impairment and hippocampal neuronal death associated with VaD.