Hydrogen saline offers neuroprotection by reducing oxidative stress in a focal cerebral ischemia-reperfusion rat model

Stroke is the second most frequent cause of death worldwide and the most frequent cause of permanent disability [1,2]. Advances in intravascular techniques and thrombolytic agents have reduced functional deficits within an optimal time window in stroke patients. However, reperfusion itself generates an over-production of reactive oxygen species (ROS), leading to reperfusion injury [3]. The burst of ROS is involved in the direct cytotoxic effects, including protein and lipid peroxidation, oxidative DNA damage, and post-ischemic inflammatory injury, through redox-mediated signaling pathways [4,5]. Therefore it is important to scavenge the free radicals and suppress the inflammation.Hydrogen gas has been used in medical applications to prevent decompression sickness (DCS) in deep divers for safety profiles [6]. In 2007, Ohsawa et al found that molecular hydrogen can selectively reduce hydroxyl radical (OH) and peroxynitrite (ONOO-) in cell-free systems and exert a therapeutic antioxidant activity in rat middle cerebral artery occlusion (MCAO) model [7]. Some other observations showed that hydrogen also had the protective effect on ischemia-reperfusion injury in the intestine, liver and heart through the inhibition of oxidant stress [8-10].Hydrogen gas would be much cheaper than other antioxidants if it could be clinically applied. However, hydrogen inhalation is not convenient and may be dangerous because it is inflammable and explosive if the concentration of hydrogen in the air is greater than 4%. On the other hand, after saturated in the physiological saline, molecule hydrogen in the saline is more easy to apply and safer than hydrogen inhalation. Considering the safety and the convenience, hydrogen saline has been prepared in our department and our previous experiments have demonstrated the neuroprotective effects of intraperitoneal hydrogen saline in a neonatal hypoxia-ischemia rat model [11]. Additionally, significantly improved post-ischemic functional recovery