3). GUA treatment suppressed this CLP effect on memory. CLP impaired the novel object recognition memory, i.e., rats

from this group did not spend a significant higher percentage of time exploring the novel object during short and long-term retention test sessions in comparison to the training trial (Fig. 4). GUA treatment suppressed this CLP effect on memory. CLP caused an increase Trichostatin A in the immobility time, compared to the sham group (Fig. 5) in the test session (5 min) of the forced swimming task, suggesting a depressive-like behavioral effect. GUA treatment suppressed this CLP effect. In the present study, we showed that GUA was effective in reversing oxidative brain damage and cognitive impairment in an animal model of sepsis, a model that is characterized by presenting cognitive impairment in survivors associated with deleterious effects caused, at least in part, by reactive oxygen species in brain tissue. Normal glutamatergic neurotransmission is essential for synaptic development Staurosporine datasheet and plasticity as well as learning and memory. In contrast, excessive glutamate excitation

plays a role in a variety of neurological disorders. Survival pathways appear to be mediated via NMDA receptor synaptic activity, whereas neuronal damage may be mediated by excessive extrasynaptic activity (Okamoto et al., Tenofovir cost 2009). Severe overstimulation of excitatory receptors can cause necrotic cell death, while less fulminant or chronic overstimulation

can cause apoptotic or other forms of cell death (Budd et al., 2000). These events are associated with overactivation of NMDA receptors that causes an excessive influx of Ca2+ ions, which trigger a series of toxic events ultimately leading to cell death by generating ROS and activating neuronal NO synthase (nNOS) (Garthwaite et al., 1988). Since GUA is thought to serve as an important local regulator of glutamatergic neurotransmission (Schmidt et al., 2007), the therapeutic value of GUA, other guanine-based purines and their analogs are under active investigation for disorders whose pathophysiology is thought to include abnormalities of NMDA receptor mediated neurotransmission (Hardingham, 2009). An extensive body of evidence from experimental and clinical studies indicates that sepsis is associated with excess glutamate release, activation of glutamate receptors that results in several metabolic alterations in the brain, such as decreased energy supplies, ATP depletion, increased ROS production, depletion of antioxidants, and accumulation of markers of oxidative stress (Dal-Pizzol et al., 2010). In an animal model, oxidative damage occurred early in the course of sepsis development in several brain regions (Barichello et al.