We verify the levels of cytokine/chemokine, myeloperoxidase activity, oxidative stress and disruption of BBB in hippocampus and cortex of the neonate Wistar rats after meningitis by S. agalactiae. In the hippocampus the levels were increased of CINC-1 at 6 h and 12 h, IL-1β at 6, 12 and 24 h, IL-6 at 6, 24 and 96 h, IL-10 at 24, 48 and 96 h and TNF-α at 24 h and 96 h. In the cortex the CINC-1 and IL-1β levels were found increased at 6 h. The MPO activity was significantly elevated at 24, 48 and 98 h in hippocampus and at 6, 12, 24, 48 and 96 h in the cortex. The breakdown of BBB started at 12 h.TBARS levels were elevated in the hippocampus at 6, 12, 24, 48, 72 and 96 h and cortex at 72 and 96 h. Protein carbonyls were elevated in the hippocampus and cortex at 6, 24, 48, 72 and 96 h. There was a decrease of SOD activity in hippocampus and in cortex. Catalase activity was elevated in hippocampus at 6 h and in the cortex at 12 and 96 h. Neonatal bacterial infections of the CNS are severe, the interference with the complex network of cytokines/chemokine, other inflammatory mediators and oxidants tend to aggravate the illness and can be involved in the breakdown of the BBB.

Nevirapine (NVP) and efavirenz (EFV) belong to the class of anti-HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), commonly used as part of highly active antiretroviral therapy (HAART). Although the HAART is able to bring down viral load to undetectable levels and restore immune function, their prolonged use causes several adverse effects. It has been demonstrated that both NVP and EFV are able to cross the blood-brain barrier, causing important central nervous system-related side effects. Thus, this study investigated the effects of chronic administration of EFV (10 mg/kg) and NVP (3.3 mg/kg) in mice submitted to two distinct series of experiments, which aimed to evaluate: (1) the emotional behavior (elevated plus-maze, forced swimming, and open-field test) and (2) the cognitive performance (object recognition and inhibitory avoidance test) of mice. Our results demonstrated that EFV, but not NVP, reduced the exploration to open arms in the elevated plus-maze test. Neither NVP nor EFV altered mouse behavior in the forced swimming and open-field tests. Both drugs reduced the recognition index in the object recognition test, but only EFV significantly impaired the aversive memory assessed in the inhibitory avoidance test 24 h after training. In conclusion, our findings point to a genuine anxiogenic-like effect to EFV, since it reduced exploration to open arms of elevated plus-maze test without affecting spontaneous locomotion. Additionally, both drugs impaired recognition memory, while only the treatment with EFV impaired significantly aversive memory.

Streptococcus agalactiae (GBS) is a major cause of severe morbidity and mortality in neonates and young infants, causing sepsis, pneumonia and meningitis. The survivors from this meningitis can suffer serious long-term neurological consequences, such as, seizures, hearing loss, learning and memory impairments. Neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) control the neuronal cell death during the brain development and play an important role in neuronal differentiation, survival and growth of neurons. Neonate Wistar rats, received either 10μL of sterile saline as a placebo or an equivalent volume of GBS suspension at a concentration of 1×10(6)cfu/mL. Sixty days after induction of meningitis, the animals underwent behavioral tests, after were killed and the hippocampus and cortex were retired for analyze of the BDNF and NGF levels. In the open-field demonstrated no difference in motor, exploratory activity and habituation memory between the groups. The step-down inhibitory avoidance, when we evaluated the long-term memory at 24h after training session, we found that the meningitis group had a decrease in aversive memory when compared with the long-term memory test of the sham group. BDNF levels decreased in hippocampus and cortex; however the NGF levels decreased only in hippocampus. These findings suggest that the meningitis model could be a good research tool for the study of the biological mechanisms involved in the behavioral alterations secondary to GBS meningitis.