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Magnesium Hydride Attenuates Cognitive Impairment in a Rat Model of Vascular Dementia

해부.생물인류학 2020년 33권 3호 p.125 ~ 134
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Abstract


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.

키워드

Magnesium hydride; Vascular dementia; 2VO/H; Hippocampal neuron

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