NLRP3 inflammasome activation increases brain oxidative stress after transient global cerebral ischemia in rats.

Pupurpose of the study: Oxidative stress has been reported to be an important mechanism for brain damage following ischemic stroke. Recently, the involvement of cytosolic receptors capable of forming protein complexes called inflammasomes has been demonstrated to perpetuate oxidative stress. Herein, we report the effect of NLRP3 inhibition with MCC950 on brain oxidative stress in an animal model of transient global cerebral ischemia.Materials and methods: Male Wistar rats received an intracerebroventricularly (icv) injection of MCC950 (140 ng/kg) or saline and were subjected to sham procedure or ischemia/reperfusion (I/R). Twenty-four hours after I/R, myeloperoxidase (MPO) activity, nitrite/nitrate (N/N) concentration, lipid peroxidation, protein carbonyls formation, superoxide dismutase (SOD) and catalase (CAT) activity were determined in the prefrontal cortex, hippocampus, cortex, cerebellum and striatum. Results: After I/R, MPO activity increased in the prefrontal cortex, hippocampus, cortex and cerebellum and N/N concentration elevated in the prefrontal cortex, hippocampus and cortex, while MCC950 decreased this level except in hippocampus. After I/R, lipid peroxidation enhanced in the prefrontal cortex and cerebellum and increased the oxidative protein damage in both structures and hippocampus. MCC950 decreased lipid peroxidation in the prefrontal cortex and decreased protein oxidative damage in all brain structures except in the striatum. SOD activity decreased in the cortex after I/R and MCC950 reestablished these levels. CAT activity decreased in the prefrontal cortex, hippocampus and cerebellum after I/R and MCC950 reestablished these levels in the prefrontal cortex.Conclusion: Our data provide novel demonstration that inhibiting NLRP3 activation with MCC950 reduces brain oxidative damage after cerebral I/R in rats.

Hyperoxia by short-term promotes oxidative damage and mitochondrial dysfunction in rat brain.

Oxygen (O2) therapy is used as a therapeutic protocol to prevent or treat hypoxia. However, a high inspired fraction of O2 (FIO2) promotes hyperoxia, a harmful condition for the central nervous system (CNS). The present study evaluated parameters of oxidative stress and mitochondrial dysfunction in the brain of rats exposed to different FIO2. Male Wistar rats were exposed to hyperoxia (FIO2 40 % and 60 %) compared to the control group (FIO2 21 %) for 2 h. Oxidative stress, neutrophilic infiltration, and mitochondrial respiratory chain enzymes were determined in the hippocampus, striatum, cerebellum, cortex, and prefrontal cortex after O2 exposure. The animals exposed to hyperoxia showed increased lipid peroxidation, formation of carbonyl proteins, N/N concentration, and neutrophilic infiltration in some brain regions, like hippocampus, striatum, and cerebellum being the most affected. Furthermore, CAT activity and activity of mitochondrial enzyme complexes were also altered after exposure to hyperoxia. Rats exposed to hyperoxia showed increase in oxidative stress parameters and mitochondrial dysfunction in brain structures.