Lactulose: an effective preventive and therapeutic option for ischemic stroke by production of hydrogen

Currently stroke is the second leading cause of death in the Western world, ranking after heart diseases and before cancer [1], causing 10% of deaths worldwide [2]. It is estimated that stroke could soon be the most common cause of death worldwide [3]. An ischemic stroke can be due to ischemia (lack of blood flow) caused by blockage (thrombosis, arterial embolism), which may lead to rapidly developing loss of brain functions as a result of disturbance in the blood supply to the brain [4]. Stroke can affect patients physically, mentally, emotionally, or a combination of the three and bring heavy burdens to society.Ischemia induces production of reactive oxygen species (ROS), which can react with and damage a number of cellular and extracellular elements. Evidence has accumulated showing that ROS are involved in cerebral ischemia and reperfusion. During cerebral ischemia, cerebral blood flow was partially or completely cut off in brain regions supplied by the occluded vessels. Reoxygenation due to spontaneous or thrombolytic reperfusion offers oxygen as a substrate for a number of enzymatic oxidation, constantly generating ROS like superoxide anion radicals(O2·-) and hydrogen peroxide(H2O2) [5]. ROS are known to be able to result in macromolecular damages including lipid peroxidation, protein oxidation, and DNA oxidation, which result in ischemic brain injury [6]. Clinically, a number of recent studies have revealed that stroke and oxidative stress are closely related and excess oxidative stress may have deleterious effects on clinical outcome in acute ischemic stroke [7,8]. Therefore, antioxidants have been considered in prevention and treatment of stroke and certain agents with antioxidative effects did have neuroprotective effects [9].In recent years, experimental evidences have documented that without influencing other less potent ROS, important in intracellular signaling, molecular hydrogen possesses the ability to selectively neutralize ONOO- and ？OH, the most c