Piroxicam reduced the intensity of epileptic seizures in a kindling seizure model.

Introduction: The close relationship between inflammatory processes and epileptic seizures is already known, although the exact pathophysiological mechanism is unclear. In this study, the anticonvulsant capacity of piroxicam, an anti-inflammatory drug, was evaluated. A rat pentylenetetrazole kindling model was used.Methods: Male Wistar rats, 8-9 weeks old, received piroxicam (0.15 and 0.30 mg/kg), diazepam (2 mg/kg) or saline for 14 days, and PTZ, on alternate days. Intraperitoneal was chosen as the route of administration. The intensity of epileptic seizures was assessed using a modified Racine scale. The open field test and object recognition analysis were performed at the beginning of the study to ensure the safety of the drugs used. At the end of the protocol, the animals were euthanized to measure the levels of inflammatory (TNF-a and IL-6) and anti-inflammatory (IL-10) cytokines in the cortex, hippocampus, and serum.Results:There were no changes in the open field test and object recognition analysis. Piroxicam was found to decrease Racine scale scores at both concentrations. The reported values for IL-6 levels remained steady in all structures, whereas the TNF-alpha level in the cortex was higher in animals treated with piroxicam than in the saline and diazepam subjects. Finally, animals treated with the anti-inflammatory drug presented reduced IL-10 levels in the cortex and hippocampus.onclusions: Using inflammation as a guiding principle, the anticonvulsant effect of PIRO could be associated with the hippocampal circuits, since this structure showed no increase in inflammatory cytokines.

Gut microbiota modulation by prednisolone in a rat kindling model of pentylenetetrazol (PTZ)-induced seizure.

The gut microbiota is a complex community composed by several microorganisms that interact in the maintenance of homeostasis and contribute to physiological processes, including brain function. The relationship of the taxonomic composition of the gut microbiota with neurological diseases such as autism, Parkinson's, Alzheimer's, anxiety, and depression is widely recognized. The immune system is an important intermediary between the gut microbiota and the central nervous system, being one of the communication routes of the gut-brain axis. Although the complexity of the relationship between inflammation and epilepsy has not yet been elucidated, inflammatory processes are similar in many ways to the consequences of dysbiosis and contribute to disease progression. This study aimed to analyze the taxonomic composition of the gut microbiota of rats treated with prednisolone in a kindling model of epilepsy. Male Wistar rats (90 days, n = 24) divided into four experimental groups: sodium chloride solution 0.9 g%, diazepam 2 mg/kg, prednisolone 1 mg/kg, and prednisolone 5 mg/kg administered intraperitoneally (i.p.) for 14 days. The kindling model was induced by pentylenetetrazole (PTZ) 25 mg/kg i.p. on alternate days. The taxonomic profile was established by applying metagenomic DNA sequencing. There was no change in alpha diversity, and the composition of the gut microbiota between prednisolone and diazepam was similar. The significant increase in Verrucomicrobia, Saccharibacteria, and Actinobacteria may be related to the protective activity against seizures and inflammatory processes that cause some cases of epilepsy. Further studies are needed to investigate the functional influence that these species have on epilepsy and the inflammatory processes that trigger it.