, 2007a and Barichello et al., 2007b). Oxidative stress is associated with a range of changes in cell function, including membrane lipid peroxidation CP-868596 cell line as well as alterations in gene and protein expression, and signaling pathways (Gunduz-Bruce, 2009). These events can be caused by abnormally intense exposure to glutamate, which

can be neurotoxic primarily through overactivation of the N-methyl-d-aspartate subtype of glutamate receptors and are associated with what we found when the animals were subjected to sepsis, in different brain regions 12 and 24 h after surgery. On the other hand, recently it has been demonstrated that GUA can act as a neuroprotective agent in an experimental model of oxidative stress injury ( Roos et al., 2009). The mechanism involved in GUA neuroprotection ( Schmidt et al., Selumetinib 2007) has been attributed to its ability to stimulate glutamate uptake in brain slices and in astrocytes, an essential neurochemical parameter involved in neuroprotection against excitotoxicity ( Danbolt, 2001 and Maragakis and Rothstein, 2001). It is possible that, in our study, GUA counteracted the oxidative damage in lipids and protein in brain regions by lowering the sepsis-induced increase

in glutamate 12 and 24 h after CLP. Furthermore, our results observed that carbonyl and TBARS show different patterns in the prefrontal cortex at 12 h and in the cortex at 24 h, in this context the free radicals can differently damage biomolecules and in this way is always important to determine more than one biomarker of oxidative damage, such as the TBARS and carbonyl. There are several differences in these techniques (sensitivity, source of radical that generates damage, repair of the damaged molecule) thus it is quite difficult to determine with precision the exact reason

to the observed difference. Intensive care unit survivors Methocarbamol experience neurologic impairments, and generally, memory is the most frequently observed deficit, followed by executive function and attention deficits. Some studies have been published with the intent to determine the molecular mechanisms associated with late memory deficits in the context of critical care medicine (Bermpohl et al., 2005, Irazuzta et al., 2005, Lehnardt et al., 2006 and Martins et al., 2005). Because oxidative stress is associated with the development of neurodegenerative disease (Halliwell, 2006) and is important to the development of a multiple organ dysfunction syndrome during sepsis (Salvemini and Cuzzocrea, 2002), it is reasonable to suppose that it could contribute to long-term memory deficits in sepsis survivors. We previously described that the short-term oxidative damage could participate in the development of central nervous system symptoms during sepsis development, or even septic encephalopathy (Barichello et al.