Therefore, the neuroprotection of GUO in cerebral ischemia could be related to its enhancement of endogenous antioxidant capacity and inhibition of reactive species production, thereby mitigating the brain damage caused by reactive species production resulting from ischemia. Glutamate excitotoxicity has long been recognized to play a key role in the pathophysiology of cerebral ischemia. Ischemia impairs glutamate uptake by EAATs, contributing to toxic amounts of the neurotransmitter into the synapse. These events result in overstimulation of glutamatergic receptors and activation of intracellular pathways that lead to cell death. Therefore, glutamate uptake activity is closely linked to ischemic events. GLAST and GLT1 are primarily expressed by astrocytes, which also express the NVP-BKM120 enzyme GS to convert glutamate to glutamine, which is then recycled to glutamate into neurons. The connected activities of these proteins contribute to maintaining the extracellular glutamate concentration below toxic levels. EAAC1, on the other hand, is predominantly expressed in neurons. The transport activities of EAAC1, GLAST and GLT1 are inhibited by oxidants via a direct action on the transporter proteins, reducing their activities. Herein, ischemic insult decreased GLT1 expression, effect reversed by GUO, and increased the neuronal EAAC1 expression, measured 24 h after ischemia. Although ischemia did not modify GS expression, its activity increased with GUO treatment after the insult. Thus, in the ischemic group, GUO potentially increased both the glutamate uptake and its intracellular conversion to glutamine. These effects may have increased removal of glutamate from the synaptic cleft in the surrounding brain area subjected to the ischemic insult. The function of EAAC1 in the brain has not been fully established. EAAC1 is a neuronal glutamate and cysteine transporter, involved in the regulation of synaptic glutamate uptake and responsible for uptake of cysteine and glutamate, precursors of GSH. In this study, EAAC1 expression significantly increased 24 h after ischemia; it could be hypothesized that this increase is an endogenous protective mechanism in response to ischemic insult. Importantly, GUO treatment increased EAAC1 expression. The correlation between the functional recovery of animals and the capacity for administration of GUO to abolish the decreased vitamin C levels, the increased ROS and RNS levels, and the increase in lipid peroxidation, demonstrates that these parameters are active participants in the pathogenesis of ischemia and the neuroprotective effects of GUO. Additionally, the recovery of essential functions of the glutamatergic system following GUO administration suggests that this is another important factor in the attenuation the tissue damage. Thus, although the mechanisms by which GUO acts are not fully known, it was demonstrated that GUO modulated maintenance of the cellular redox environment and the glutamatergic system following ischemic injury in rodents.