This effect was maintained up to 15 days post-insult, and also significantly reduced the cerebral infarct volume. Moreover, GUO treatment significantly abolished the increase in lipid peroxidation caused by ischemia. Thus, GUO treatment was able to restore clinical sensorimotor function, decreased the associated morphological brain damage and abolished the neural cell membrane damage. These results demonstrate an effective neuroprotective role of GUO against ischemic insult to the brain. The mechanisms of neuroprotective strategies against cerebral ischemia may target biochemical alterations involved in cellular damage and/or improve hemostatic and vascular systems involved in collateral blood flow. As the precise GUO neuroprotective mechanisms are unclear, this study aimed to search for putative intracellular biochemical parameters in neural cells involved in this neuroprotection. Here, it was demonstrated for the first time that GUO treatment modulated important parameters related to both the oxidative BMN673 PARP inhibitor stress response and the glutamatergic system after an in vivo ischemic event. Free radicals play an essential role in maintaining the physiological condition of the body. Because the CNS has a high oxidative metabolism rate, brain cells are especially vulnerable to free radical damage during ischemia. Defense against free radicals is provided by a number of antioxidant enzymes, including SOD, CAT and GPx. SOD converts O2 2 to H2O2, whereas CAT and GPx convert H2O2 to H2O, thus removing ROS. These enzymes are coupled with other non-enzymatic antioxidants, such as GSH and vitamin C, responsible for reducing both ROS and RNS levels. During an ischemic event, there is a massive production of ROS and RNS that depletes intracellular brain GSH and vitamin C levels. Despite increased expression of antioxidant enzymes during ischemic injury, there is an impairment of their activities, which implies a severe state of oxidative stress and enhanced lipid peroxidation rates. Here, the ischemic insult increased SOD expression and decreased SOD activity; GUO treatment increased SOD expression and completely reestablished SOD activity. Studies have shown that overexpression of SOD in transgenic mice resulted in a reduction of infarction volume and better neurological outcomes after ischemia. The increased CAT activity in the ischemic animals treated with GUO could be a beneficial response designed to remove H2O2. In this context, modulation of the expression and activity of SOD and the CAT activity by GUO may indicate that the neuroprotective effects of GUO are associated with attenuation of oxidative stress, consequently decreasing free radical levels. Mounting evidence suggests that radical scavengers mediate protective effects following cerebral ischemia. Studies have shown vitamin C is neuroprotective during ischemia, decreasing infarct volume, and this effect is likely related to scavenging for reactive species. In the current study, ischemic insult decreased the levels of the non-enzymatic scavenger compounds GSH and vitamin C; although GUO treatment was not able to reverse the decreased GSH levels, GUO treatment did reverse the decreased vitamin C levels.