Stroke is the third leading cause of death and an important factor that may affect morbidity and long-term disability. It has been suggested that ischemic stroke may result in the interruption and/or severe reduction of blood flow in cerebral arteries.1) The brain has an absolute dependence on the blood for its immediate supply of oxygen and energy substrates.2)The depletion of energy stores influenced by interruption of the cerebral blood flow can cause several acute metabolic disturbances, such as disruption of ion homeostasis, massive release of excitotoxic amino acids, and free radical formation. The energy failure may lead to membrane depolarization, thus causing reduced activity of ATP-dependent ion pump, Na ϩ /K ϩ -ATPase, which regulates the ionic concentration gradients needed to generate action potentials by neurons.3) The subsequent depolarization of membranes leads to activated glutamate receptors, of which the N-methyl-D-aspartate (NMDA) and a-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors are clearly implicated in neurotoxicity, and consequently a further increase in Ca 2ϩ levels.2,4,5) Elevated intracellular Ca 2ϩ causes an increase in cellular oxidative stress that contributes to cell damage, and activates various enzymes such as lipases, proteases, and endonucleases that may damage DNA, cell proteins, and lipids, thus leading to cellular death. 4,6) It has been indicated that oxidative stress is considered one of the primary risk factors that exacerbate the damage by cerebral ischemia.7) Several components of reactive oxygen species (ROS) generated after ischemia/reperfusion injury, ), are known to promote DNA damage, peroxidation of lipids, proteins and carbohydrates, blood brain-barrier break-down, and microglial infiltration in the ischemic territory. 4,8,9) Experimental ischemia/reperfusion models have been extensively studied, [15][16][17] and the cumulative evidence suggests involvement of oxygen radicals in the pathogenesis of ischemic lesions. ] i , and inhibiting glutamate release and generation of ROS, and that the neuroprotective effect of SR against focal cerebral ischemic injury is due to its anti-oxidative effects. Thus SR might have therapeutic roles in neurodegenerative diseases such as stroke.
